IL-2 gene expression and NF-kappa B activation through CD28 requires reactive oxygen production by 5-lipoxygenase .

<dna>IL-2 gene</dna> expression and <protein>NF-kappa B</protein> activation through <protein>CD28</protein> requires reactive oxygen production by <protein>5-lipoxygenase</protein> .


Activation of the CD28 surface receptor provides a major costimulatory signal for T cell activation resulting in enhanced production of interleukin-2 ( IL-2 ) and cell proliferation .

Activation of the <protein>CD28 surface receptor</protein> provides a major costimulatory signal for T cell activation resulting in enhanced production of <protein>interleukin-2</protein> ( <protein>IL-2</protein> ) and cell proliferation .


In primary T lymphocytes we show that CD28 ligation leads to the rapid intracellular formation of reactive oxygen intermediates ( ROIs ) which are required for CD28 -mediated activation of the NF-kappa B / CD28-responsive complex and IL-2 expression .

In <cell_type>primary T lymphocytes</cell_type> we show that <protein>CD28</protein> ligation leads to the rapid intracellular formation of reactive oxygen intermediates ( ROIs ) which are required for <protein>CD28</protein> -mediated activation of the <protein>NF-kappa B</protein> / <protein>CD28-responsive complex</protein> and <protein>IL-2</protein> expression .


Delineation of the CD28 signaling cascade was found to involve protein tyrosine kinase activity , followed by the activation of phospholipase A2 and 5-lipoxygenase .

Delineation of the <protein>CD28</protein> signaling cascade was found to involve <protein>protein tyrosine kinase</protein> activity , followed by the activation of <protein>phospholipase A2</protein> and <protein>5-lipoxygenase</protein> .


Our data suggest that lipoxygenase metabolites activate ROI formation which then induce IL-2 expression via NF-kappa B activation .

Our data suggest that <protein>lipoxygenase metabolites</protein> activate ROI formation which then induce <protein>IL-2</protein> expression via <protein>NF-kappa B</protein> activation .


These findings should be useful for therapeutic strategies and the development of immunosuppressants targeting the CD28 costimulatory pathway .

These findings should be useful for therapeutic strategies and the development of immunosuppressants targeting the <protein>CD28</protein> costimulatory pathway .


The peri-kappa B site mediates human immunodeficiency virus type 2 enhancer activation in monocytes but not in T cells .

The <dna>peri-kappa B site</dna> mediates <dna>human immunodeficiency virus type 2 enhancer</dna> activation in <cell_type>monocytes</cell_type> but not in <cell_type>T cells</cell_type> .


Human immunodeficiency virus type 2 ( HIV-2 ) , like HIV-1 , causes AIDS and is associated with AIDS cases primarily in West Africa .


HIV-1 and HIV-2 display significant differences in nucleic acid sequence and in the natural history of clinical disease .


Consistent with these differences , we have previously demonstrated that the enhancer/promoter region of HIV-2 functions quite differently from that of HIV-1 .

Consistent with these differences , we have previously demonstrated that the <dna>enhancer/promoter region</dna> of HIV-2 functions quite differently from that of HIV-1 .


Whereas activation of the HIV-1 enhancer following T-cell stimulation is mediated largely through binding of the transcription factor NF-kappa B to two adjacent kappa B sites in the HIV-1 long terminal repeat , activation of the HIV-2 enhancer in monocytes and T cells is dependent on four cis-acting elements : a single kappa B site , two purine-rich binding sites , PuB1 and PuB2 , and a pets site .

Whereas activation of the <dna>HIV-1 enhancer</dna> following T-cell stimulation is mediated largely through binding of the <protein>transcription factor</protein> <protein>NF-kappa B</protein> to two adjacent <dna>kappa B sites</dna> in the <dna>HIV-1 long terminal repeat</dna> , activation of the <dna>HIV-2 enhancer</dna> in <cell_type>monocytes</cell_type> and <cell_type>T cells</cell_type> is dependent on four <dna>cis-acting elements</dna> : a single <dna>kappa B site</dna> , two <dna>purine-rich binding sites</dna> , <dna>PuB1</dna> and <dna>PuB2</dna> , and a <dna>pets site</dna> .


We have now identified a novel cis-acting element within the HIV-2 enhancer , immediately upstream of the kappa B site , designated peri-kappa B .

We have now identified a novel <dna>cis-acting element</dna> within the <dna>HIV-2 enhancer</dna> , immediately upstream of the <dna>kappa B site</dna> , designated <dna>peri-kappa B</dna> .


This site is conserved among isolates of HIV-2 and the closely related simian immunodeficiency virus , and transfection assays show this site to mediate HIV-2 enhancer activation following stimulation of monocytic but not T-cell lines .

This site is conserved among isolates of HIV-2 and the closely related simian immunodeficiency virus , and transfection assays show this site to mediate <dna>HIV-2 enhancer</dna> activation following stimulation of <cell_line>monocytic</cell_line> but not <cell_line>T-cell lines</cell_line> .


This is the first description of an HIV-2 enhancer element which displays such monocyte specificity , and no comparable enhancer element has been clearly defined for HIV-1 .

This is the first description of an <dna>HIV-2 enhancer element</dna> which displays such monocyte specificity , and no comparable <dna>enhancer element</dna> has been clearly defined for HIV-1 .


While a nuclear factor ( s ) from both peripheral blood monocytes and T cells binds the peri-kappa B site , electrophoretic mobility shift assays suggest that either a different protein binds to this site in monocytes versus T cells or that the protein recognizing this enhancer element undergoes differential modification in monocytes and T cells , thus supporting the transfection data .

While a <protein>nuclear factor</protein> ( s ) from both <cell_type>peripheral blood monocytes</cell_type> and <cell_type>T cells</cell_type> binds the <dna>peri-kappa B site</dna> , electrophoretic mobility shift assays suggest that either a different protein binds to this site in <cell_type>monocytes</cell_type> versus <cell_type>T cells</cell_type> or that the protein recognizing this <dna>enhancer element</dna> undergoes differential modification in <cell_type>monocytes</cell_type> and <cell_type>T cells</cell_type> , thus supporting the transfection data .


Further , while specific constitutive binding to the peri-kappa B site is seen in monocytes , stimulation with phorbol esters induces additional , specific binding .

Further , while specific constitutive binding to the <dna>peri-kappa B site</dna> is seen in <cell_type>monocytes</cell_type> , stimulation with phorbol esters induces additional , specific binding .


Understanding the monocyte-specific function of the peri-kappa B factor may ultimately provide insight into the different role monocytes and T cells play in HIV pathogenesis .

Understanding the monocyte-specific function of the <protein>peri-kappa B factor</protein> may ultimately provide insight into the different role <cell_type>monocytes</cell_type> and <cell_type>T cells</cell_type> play in HIV pathogenesis .


E1A gene expression induces susceptibility to killing by NK cells following immortalization but not adenovirus infection of human cells .

<dna>E1A gene</dna> expression induces susceptibility to killing by <cell_type>NK cells</cell_type> following immortalization but not adenovirus infection of <cell_type>human cells</cell_type> .


Adenovirus ( Ad ) infection and E1A transfection were used to model changes in susceptibility to NK cell killing caused by transient vs stable E1A expression in human cells .

Adenovirus ( Ad ) infection and <protein>E1A</protein> transfection were used to model changes in susceptibility to NK cell killing caused by transient vs stable <protein>E1A</protein> expression in <cell_type>human cells</cell_type> .


Only stably transfected target cells exhibited cytolytic susceptibility , despite expression of equivalent levels of E1A proteins in Ad-infected targets .

Only stably <cell_line>transfected target cells</cell_line> exhibited cytolytic susceptibility , despite expression of equivalent levels of <protein>E1A proteins</protein> in <cell_line>Ad-infected targets</cell_line> .


The inability of E1A gene products to induce cytolytic susceptibility during infection was not explained by an inhibitory effect of viral infection on otherwise susceptible target cells or by viral gene effects on class I MHC antigen expression on target cells .

The inability of <dna>E1A gene</dna> products to induce cytolytic susceptibility during infection was not explained by an inhibitory effect of viral infection on otherwise susceptible <cell_type>target cells</cell_type> or by <dna>viral gene</dna> effects on <protein>class I MHC antigen</protein> expression on <cell_type>target cells</cell_type> .


This differential effect of E1A expression on the cytolytic phenotypes of infected and stably transfected human cells suggests that human NK cells provide an effective immunologic barrier against the in vivo survival and neoplastic progression of E1A-immortalized cells that may emerge from the reservoir of persistently infected cells in the human host .

This differential effect of <protein>E1A</protein> expression on the cytolytic phenotypes of infected and stably transfected <cell_type>human cells</cell_type> suggests that <cell_type>human NK cells</cell_type> provide an effective immunologic barrier against the in vivo survival and neoplastic progression of <cell_line>E1A-immortalized cells</cell_line> that may emerge from the reservoir of <cell_type>persistently infected cells</cell_type> in the human host .


Distinct signaling properties identify functionally different CD4 epitopes .

Distinct signaling properties identify functionally different <protein>CD4 epitopes</protein> .


The CD4 coreceptor interacts with non-polymorphic regions of major histocompatibility complex class II molecules on antigen-presenting cells and contributes to T cell activation .

The <protein>CD4 coreceptor</protein> interacts with <protein>non-polymorphic regions</protein> of <protein>major histocompatibility complex class II molecules</protein> on <cell_type>antigen-presenting cells</cell_type> and contributes to T cell activation .


We have investigated the effect of CD4 triggering on T cell activating signals in a lymphoma model using monoclonal antibodies ( mAb ) which recognize different CD4 epitopes .

We have investigated the effect of <protein>CD4</protein> triggering on T cell activating signals in a lymphoma model using <protein>monoclonal antibodies</protein> ( <protein>mAb</protein> ) which recognize different <protein>CD4 epitopes</protein> .


We demonstrate that CD4 triggering delivers signals capable of activating the NF-AT transcription factor which is required for interleukin-2 gene expression .

We demonstrate that <protein>CD4</protein> triggering delivers signals capable of activating the <protein>NF-AT transcription factor</protein> which is required for <protein>interleukin-2</protein> gene expression .


Whereas different anti-CD4 mAb or HIV-1 gp120 could all trigger activation of the protein tyrosine kinases p56lck and p59fyn and phosphorylation of the Shc adaptor protein , which mediates signals to Ras , they differed significantly in their ability to activate NF-AT .

Whereas different <protein>anti-CD4 mAb</protein> or <protein>HIV-1 gp120</protein> could all trigger activation of the <protein>protein tyrosine kinases</protein> <protein>p56lck</protein> and <protein>p59fyn</protein> and phosphorylation of the <protein>Shc adaptor protein</protein> , which mediates signals to <protein>Ras</protein> , they differed significantly in their ability to activate <protein>NF-AT</protein> .


Lack of full activation of NF-AT could be correlated to a dramatically reduced capacity to induce calcium flux and could be complemented with a calcium ionophore .

Lack of full activation of <protein>NF-AT</protein> could be correlated to a dramatically reduced capacity to induce calcium flux and could be complemented with a calcium ionophore .


The results identify functionally distinct epitopes on the CD4 coreceptor involved in activation of the Ras/protein kinase C and calcium pathways .

The results identify functionally distinct <protein>epitopes</protein> on the <protein>CD4 coreceptor</protein> involved in activation of the <protein>Ras/protein kinase C</protein> and calcium pathways .


Ligand-dependent repression of the erythroid transcription factor GATA-1 by the estrogen receptor .

Ligand-dependent repression of the <protein>erythroid transcription factor</protein> <protein>GATA-1</protein> by the <protein>estrogen receptor</protein> .


High-dose estrogen administration induces anemia in mammals .


In chickens , estrogens stimulate outgrowth of bone marrow-derived erythroid progenitor cells and delay their maturation .

In chickens , estrogens stimulate outgrowth of <cell_type>bone marrow-derived erythroid progenitor cells</cell_type> and delay their maturation .


This delay is associated with down-regulation of many erythroid cell-specific genes , including alpha- and beta-globin , band 3 , band 4.1 , and the erythroid cell-specific histone H5 .

This delay is associated with down-regulation of many <dna>erythroid cell-specific genes</dna> , including <dna>alpha- and beta-globin</dna> , band 3 , band 4.1 , and the <protein>erythroid cell-specific histone</protein> <protein>H5</protein> .


We show here that estrogens also reduce the number of erythroid progenitor cells in primary human bone marrow cultures .

We show here that estrogens also reduce the number of <cell_type>erythroid progenitor cells</cell_type> in <cell_line>primary human bone marrow cultures</cell_line> .


To address potential mechanisms by which estrogens suppress erythropoiesis , we have examined their effects on GATA-1 , an erythroid transcription factor that participates in the regulation of the majority of erythroid cell-specific genes and is necessary for full maturation of erythrocytes .

To address potential mechanisms by which estrogens suppress erythropoiesis , we have examined their effects on <protein>GATA-1</protein> , an <protein>erythroid transcription factor</protein> that participates in the regulation of the majority of <dna>erythroid cell-specific genes</dna> and is necessary for full maturation of <cell_type>erythrocytes</cell_type> .


We demonstrate that the transcriptional activity of GATA-1 is strongly repressed by the estrogen receptor ( ER ) in a ligand-dependent manner and that this repression is reversible in the presence of 4-hydroxytamoxifen .

We demonstrate that the transcriptional activity of <protein>GATA-1</protein> is strongly repressed by the <protein>estrogen receptor</protein> ( <protein>ER</protein> ) in a ligand-dependent manner and that this repression is reversible in the presence of 4-hydroxytamoxifen .


ER -mediated repression of GATA-1 activity occurs on an artificial promoter containing a single GATA-binding site , as well as in the context of an intact promoter which is normally regulated by GATA-1 .

<protein>ER</protein> -mediated repression of <protein>GATA-1</protein> activity occurs on an <dna>artificial promoter</dna> containing a single <dna>GATA-binding site</dna> , as well as in the context of an <dna>intact promoter</dna> which is normally regulated by <protein>GATA-1</protein> .


GATA-1 and ER bind to each other in vitro in the absence of DNA .

<protein>GATA-1</protein> and <protein>ER</protein> bind to each other in vitro in the absence of DNA .


In coimmunoprecipitation experiments using transfected COS cells , GATA-1 and ER associate in a ligand-dependent manner .

In coimmunoprecipitation experiments using transfected <cell_line>COS cells</cell_line> , <protein>GATA-1</protein> and <protein>ER</protein> associate in a ligand-dependent manner .


Mapping experiments indicate that GATA-1 and the ER form at least two contacts , which involve the finger region and the N-terminal activation domain of GATA-1 .

Mapping experiments indicate that <protein>GATA-1</protein> and the <protein>ER</protein> form at least two contacts , which involve the finger region and the <protein>N-terminal activation domain</protein> of <protein>GATA-1</protein> .


We speculate that estrogens exert effects on erythropoiesis by modulating GATA-1 activity through protein-protein interaction with the ER .

We speculate that estrogens exert effects on erythropoiesis by modulating <protein>GATA-1</protein> activity through protein-protein interaction with the <protein>ER</protein> .


( ABSTRACT TRUNCATED AT 250 WORDS )


Mouse interleukin-2 receptor alpha gene expression .

<dna>Mouse interleukin-2 receptor alpha gene</dna> expression .


Interleukin-1 and interleukin-2 control transcription via distinct cis-acting elements .

<protein>Interleukin-1</protein> and <protein>interleukin-2</protein> control transcription via distinct <dna>cis-acting elements</dna> .


We have shown that interleukin-1 ( IL-1 ) and IL-2 control IL-2 receptor alpha ( IL-2R alpha ) gene transcription in CD4-CD8- murine T lymphocyte precursors .

We have shown that <protein>interleukin-1</protein> ( <protein>IL-1</protein> ) and <protein>IL-2</protein> control <dna>IL-2 receptor alpha ( IL-2R alpha ) gene</dna> transcription in <cell_line>CD4-CD8- murine T lymphocyte precursors</cell_line> .


Here we map the cis-acting elements that mediate interleukin responsiveness of the mouse IL-2R alpha gene using a thymic lymphoma-derived hybridoma ( PC60 ) .

Here we map the <dna>cis-acting elements</dna> that mediate interleukin responsiveness of the <dna>mouse IL-2R alpha gene</dna> using a <cell_line>thymic lymphoma-derived hybridoma</cell_line> ( <cell_line>PC60</cell_line> ) .


The transcriptional response of the IL-2R alpha gene to stimulation by IL-1 + IL-2 is biphasic .

The transcriptional response of the <dna>IL-2R alpha gene</dna> to stimulation by <protein>IL-1</protein> + <protein>IL-2</protein> is biphasic .


IL-1 induces a rapid , protein synthesis-independent appearance of IL-2R alpha mRNA that is blocked by inhibitors of NF-kappa B activation .

<protein>IL-1</protein> induces a rapid , protein synthesis-independent appearance of <rna>IL-2R alpha mRNA</rna> that is blocked by inhibitors of <protein>NF-kappa B</protein> activation .


It also primes cells to become IL-2 responsive and thereby prepares the second phase , in which IL-2 induces a 100-fold further increase in IL-2R alpha transcripts .

It also primes cells to become <protein>IL-2</protein> responsive and thereby prepares the second phase , in which <protein>IL-2</protein> induces a 100-fold further increase in <rna>IL-2R alpha transcripts</rna> .


Transient transfection experiments show that several elements in the promoter-proximal region of the IL-2R alpha gene contribute to IL-1 responsiveness , most importantly an NF-kappa B site conserved in the human and mouse gene .

Transient transfection experiments show that several elements in the <dna>promoter-proximal region</dna> of the <dna>IL-2R alpha gene</dna> contribute to <protein>IL-1</protein> responsiveness , most importantly an <dna>NF-kappa B site</dna> conserved in the <dna>human and mouse gene</dna> .


IL-2 responsiveness , on the other hand , depends on a 78-nucleotide segment 1.3 kilobases upstream of the major transcription start site .

<protein>IL-2</protein> responsiveness , on the other hand , depends on a <dna>78-nucleotide segment</dna> 1.3 kilobases upstream of the <dna>major transcription start site</dna> .


This segment functions as an IL-2-inducible enhancer and lies within a region that becomes DNase I hypersensitive in normal T cells in which IL-2R alpha expression has been induced .

This segment functions as an <dna>IL-2-inducible enhancer</dna> and lies within a region that becomes <protein>DNase I</protein> hypersensitive in normal <cell_type>T cells</cell_type> in which <protein>IL-2R alpha</protein> expression has been induced .


IL-2 responsiveness requires three distinct elements within the enhancer .

<protein>IL-2</protein> responsiveness requires three distinct <dna>elements</dna> within the <dna>enhancer</dna> .


Two of these are potential binding sites for STAT proteins .

Two of these are potential binding sites for <protein>STAT proteins</protein> .


Hematopoietic lineage commitment : role of transcription factors .

<cell_type>Hematopoietic lineage</cell_type> commitment : role of <protein>transcription factors</protein> .


This review focuses on the roles of transcription factors in hematopoietic lineage commitment .

This review focuses on the roles of <protein>transcription factors</protein> in hematopoietic lineage commitment .


A brief introduction to lineage commitment and asymmetric cell division is followed by a discussion of several methods used to identify transcription factors important in specifying hematopoietic cell types .

A brief introduction to lineage commitment and asymmetric cell division is followed by a discussion of several methods used to identify <protein>transcription factors</protein> important in specifying <cell_type>hematopoietic cell types</cell_type> .


Next is presented a discussion of the use of embryonic stem cells in the analysis of hematopoietic gene expression and the use of targeted gene disruption to analyze the role of transcription factors in hematopoiesis .

Next is presented a discussion of the use of <cell_type>embryonic stem cells</cell_type> in the analysis of <dna>hematopoietic gene</dna> expression and the use of targeted gene disruption to analyze the role of <protein>transcription factors</protein> in hematopoiesis .


Finally , the status of our current knowledge concerning the roles of transcription factors in the commitment to erythroid , myeloid and lymphoid cell types is summarized .

Finally , the status of our current knowledge concerning the roles of <protein>transcription factors</protein> in the commitment to <cell_type>erythroid , myeloid and lymphoid cell types</cell_type> is summarized .


Epstein-Barr virus replicative gene transcription during de novo infection of human thymocytes : simultaneous early expression of BZLF-1 and its repressor RAZ .

Epstein-Barr virus replicative gene transcription during de novo infection of <cell_type>human thymocytes</cell_type> : simultaneous early expression of <protein>BZLF-1</protein> and its repressor <protein>RAZ</protein> .


Epstein-Barr virus ( EBV ) is known to infect B cells and epithelial cells .

Epstein-Barr virus ( EBV ) is known to infect <cell_type>B cells</cell_type> and <cell_type>epithelial cells</cell_type> .


We and others have shown that EBV can also infect a subset of thymocytes .

We and others have shown that EBV can also infect a subset of <cell_type>thymocytes</cell_type> .


Infection of thymocytes was accompanied by the appearance of linear EBV genome within 8 hr of infection .

Infection of <cell_type>thymocytes</cell_type> was accompanied by the appearance of <dna>linear EBV genome</dna> within 8 hr of infection .


Circularization of the EBV genome was not detected .

Circularization of the <dna>EBV genome</dna> was not detected .


This is in contrast to the infection in B cells where the genome can circularize within 24 hr of infection .

This is in contrast to the infection in <cell_type>B cells</cell_type> where the genome can circularize within 24 hr of infection .


The appearance of the BamHI ZLF-1 gene product , ZEBRA , by RT-PCR , was observed within 8 hr of infection .

The appearance of the <protein>BamHI ZLF-1 gene product</protein> , <protein>ZEBRA</protein> , by RT-PCR , was observed within 8 hr of infection .


The appearance of a novel fusion transcript ( RAZ ) , which comprised regions of the BZLF-1 locus and the adjacent BRLF-1 locus , was detected by RT-PCR .

The appearance of a novel <protein>fusion transcript</protein> ( <protein>RAZ</protein> ) , which comprised regions of the <dna>BZLF-1 locus</dna> and the adjacent <dna>BRLF-1 locus</dna> , was detected by RT-PCR .


ZEBRA protein was also identified in infected thymocytes by immunoprecipitation .

<protein>ZEBRA protein</protein> was also identified in infected <cell_type>thymocytes</cell_type> by immunoprecipitation .


In addition , we demonstrated that the EBNA-1 gene in infected thymocytes was transcribed from the Fp promoter , rather than from the Cp/Wp promoter which is used in latently infected B cells .

In addition , we demonstrated that the <dna>EBNA-1 gene</dna> in infected <cell_type>thymocytes</cell_type> was transcribed from the <dna>Fp promoter</dna> , rather than from the <dna>Cp/Wp promoter</dna> which is used in <cell_type>latently infected B cells</cell_type> .


Transcripts encoding gp350/220 , the major coat protein of EBV , were identified , but we did not find any evidence of transcription from the LMP-2A or EBER-1 loci in infected thymocytes .

Transcripts encoding <protein>gp350/220</protein> , the <protein>major coat protein</protein> of EBV , were identified , but we did not find any evidence of transcription from the <dna>LMP-2A</dna> or <dna>EBER-1 loci</dna> in infected <cell_type>thymocytes</cell_type> .


These observations suggest that de novo EBV infection of thymocytes differs from infection of B cells .

These observations suggest that de novo EBV infection of <cell_type>thymocytes</cell_type> differs from infection of <cell_type>B cells</cell_type> .


The main difference is that with thymocytes , no evidence could be found that the virus ever circularizes .

The main difference is that with <cell_type>thymocytes</cell_type> , no evidence could be found that the virus ever circularizes .


Rather , EBV remains in a linear configuration from which replicative genes are transcribed .

Rather , EBV remains in a linear configuration from which <dna>replicative genes</dna> are transcribed .


Identification and purification of human Stat proteins activated in response to interleukin-2 .

Identification and purification of <protein>human Stat proteins</protein> activated in response to <protein>interleukin-2</protein> .


A key cytokine induced during the immune response is IL-2 .

A key <protein>cytokine</protein> induced during the immune response is <protein>IL-2</protein> .


Following T cell activation , the genes encoding IL-2 and the various chains of its receptor are transcriptionally induced .

Following T cell activation , the genes encoding <protein>IL-2</protein> and the various chains of its receptor are transcriptionally induced .


In turn , secreted IL-2 serves to stimulate the proliferation and differentiation of T lymphocytes .

In turn , secreted <protein>IL-2</protein> serves to stimulate the proliferation and differentiation of <cell_type>T lymphocytes</cell_type> .


Several recent studies have implicated Jak kinases in the signaling pathway induced by IL-2 .

Several recent studies have implicated Jak kinases in the signaling pathway induced by <protein>IL-2</protein> .


Following this lead , we set out to identify transcription factors induced in response to IL-2 .

Following this lead , we set out to identify <protein>transcription factors</protein> induced in response to <protein>IL-2</protein> .


Human peripheral blood lymphocytes were observed to contain several IL-2 -inducible DNA binding activities .

<cell_type>Human peripheral blood lymphocytes</cell_type> were observed to contain several <protein>IL-2</protein> -inducible DNA binding activities .


Similar activities were also observed in a transformed human lymphocyte line , termed YT .

Similar activities were also observed in a <cell_line>transformed human lymphocyte line</cell_line> , termed <cell_line>YT</cell_line> .


We have purified these activities and found that the principal IL-2-inducible component bears significant relatedness to a prolactin-induced transcription factor first identified in sheep mammary gland tissue .

We have purified these activities and found that the principal <protein>IL-2-inducible component</protein> bears significant relatedness to a <protein>prolactin-induced transcription factor</protein> first identified in <cell_type>sheep mammary gland tissue</cell_type> .


We hypothesize that activation of this protein , designated hStat5 , helps govern the biological effects of IL-2 during the immune response .

We hypothesize that activation of this protein , designated <protein>hStat5</protein> , helps govern the biological effects of <protein>IL-2</protein> during the immune response .


E2F-1 and a cyclin-like DNA repair enzyme , uracil-DNA glycosylase , provide evidence for an autoregulatory mechanism for transcription .

<protein>E2F-1</protein> and a <protein>cyclin-like DNA repair enzyme</protein> , <protein>uracil-DNA glycosylase</protein> , provide evidence for an autoregulatory mechanism for transcription .


The cell cycle-dependent transcription factor , E2F-1 , regulates the cyclin -like species of the DNA repair enzyme uracil-DNA glycosylase ( UDG ) gene in human osteosarcoma ( Saos-2 ) cells .

The <protein>cell cycle-dependent transcription factor</protein> , <protein>E2F-1</protein> , regulates the <protein>cyclin</protein> -like species of the <protein>DNA repair enzyme</protein> <dna>uracil-DNA glycosylase ( UDG ) gene</dna> in <cell_line>human osteosarcoma ( Saos-2 ) cells</cell_line> .


We demonstrate , through the deletion of the human UDG promoter sequences , that expression of E2F-1 activates the UDG promoter through several E2F sites .

We demonstrate , through the deletion of the <dna>human UDG promoter sequences</dna> , that expression of <protein>E2F-1</protein> activates the <dna>UDG promoter</dna> through several <dna>E2F sites</dna> .


The major putative downstream site for E2F , located in the first exon , serves as a target for E2F-1/DP1 complex binding in vitro .

The <dna>major putative downstream site</dna> for <protein>E2F</protein> , located in the <dna>first exon</dna> , serves as a target for <protein>E2F-1/DP1 complex</protein> binding in vitro .


We also provide evidence for the functional relationship between the cyclin-like UDG gene product and E2F .

We also provide evidence for the functional relationship between the <protein>cyclin-like UDG gene product</protein> and <protein>E2F</protein> .


High levels of UDG expression in a transient transfection assay result in the down-regulation of transcriptional activity through elements specific for E2F -mediated transcription .

High levels of <protein>UDG</protein> expression in a transient transfection assay result in the down-regulation of transcriptional activity through <dna>elements</dna> specific for <protein>E2F</protein> -mediated transcription .


Overexpression of UDG in Saos 2 cells was observed to delay growth late in G1 phase and transiently arrest these cells from progressing into the S phase .

Overexpression of <protein>UDG</protein> in <cell_line>Saos 2 cells</cell_line> was observed to delay growth late in G1 phase and transiently arrest these cells from progressing into the S phase .


This hypothetical model integrates one mechanism of DNA repair with the cell cycle control of gene transcription , likely through E2F .

This hypothetical model integrates one mechanism of DNA repair with the cell cycle control of gene transcription , likely through <protein>E2F</protein> .


This implicates E2F as a multifunctional target for proteins and enzymes , possibly , responsive to DNA damage through the negative effect of UDG on E2F -mediated transcriptional activity .

This implicates <protein>E2F</protein> as a multifunctional target for proteins and enzymes , possibly , responsive to DNA damage through the negative effect of <protein>UDG</protein> on <protein>E2F</protein> -mediated transcriptional activity .


Cellular and molecular mechanisms of IFN-gamma production induced by IL-2 and IL-12 in a human NK cell line .

Cellular and molecular mechanisms of <protein>IFN-gamma</protein> production induced by <protein>IL-2</protein> and <protein>IL-12</protein> in a <cell_line>human NK cell line</cell_line> .


Interferon-gamma ( IFN-gamma ) is an important immunoregulatory protein produced predominantly by T cells and large granular lymphocytes ( LGL ) in response to different extracellular signals .

<protein>Interferon-gamma</protein> ( <protein>IFN-gamma</protein> ) is an important <protein>immunoregulatory protein</protein> produced predominantly by <cell_type>T cells</cell_type> and <cell_type>large granular lymphocytes</cell_type> ( <cell_type>LGL</cell_type> ) in response to different extracellular signals .


In particular , two interleukins ( ILs ) , IL-2 and IL-12 , have been shown to be potent inducers of IFN-gamma gene expression in both T cells and LGL .

In particular , two <protein>interleukins</protein> ( <protein>ILs</protein> ) , <protein>IL-2</protein> and <protein>IL-12</protein> , have been shown to be potent inducers of <protein>IFN-gamma</protein> gene expression in both <cell_type>T cells</cell_type> and <cell_type>LGL</cell_type> .


Although it has been reported that there are some T cell lines that produce IFN-gamma in response to IL-2 and IL-12 stimulation , there has as yet been no report of a natural killer ( NK ) cell line that responds in a similar manner .

Although it has been reported that there are some <cell_line>T cell lines</cell_line> that produce <protein>IFN-gamma</protein> in response to IL-2 and IL-12 stimulation , there has as yet been no report of a <cell_line>natural killer ( NK ) cell line</cell_line> that responds in a similar manner .


In this report we present evidence that the cell line NK3.3 derived from human NK cells , responds to both IL-2 and IL-12 , as measured by increases in IFN-gamma and granulocyte-macrophage colony-stimulating factor ( GM-CSF ) cytoplasmic mRNA and protein expression .

In this report we present evidence that the <cell_line>cell line NK3.3</cell_line> derived from <cell_type>human NK cells</cell_type> , responds to both <protein>IL-2</protein> and <protein>IL-12</protein> , as measured by increases in <protein>IFN-gamma</protein> and <protein>granulocyte-macrophage colony-stimulating factor</protein> ( <protein>GM-CSF</protein> ) cytoplasmic mRNA and protein expression .


In addition , when used together IL-2 and IL-12 synergized in the induction of IFN-gamma and GM-CSF and this synergy was attributed to an increased accumulation and stability of the IFN-gamma and GM-CSF mRNAs .

In addition , when used together <protein>IL-2</protein> and <protein>IL-12</protein> synergized in the induction of <protein>IFN-gamma</protein> and <protein>GM-CSF</protein> and this synergy was attributed to an increased accumulation and stability of the <rna>IFN-gamma and GM-CSF mRNAs</rna> .


To investigate the signaling pathways involved in the gene induction , five inhibitors , cyclosporin A ( CsA ) , transforming growth factor-beta , cycloheximide , genistein , and staurosporine A , were used in analyzing the effects of IL-2 and IL-12 on NK3.3 cells .

To investigate the signaling pathways involved in the gene induction , five inhibitors , cyclosporin A ( CsA ) , <protein>transforming growth factor-beta</protein> , cycloheximide , genistein , and staurosporine A , were used in analyzing the effects of <protein>IL-2</protein> and <protein>IL-12</protein> on <cell_line>NK3.3 cells</cell_line> .


The results suggest that activation of protein kinase C , but not new protein synthesis , is required for IL-2 induction of IFN-gamma and GM-CSF cytoplasmic mRNA .

The results suggest that activation of <protein>protein kinase C</protein> , but not new protein synthesis , is required for <protein>IL-2</protein> induction of <rna>IFN-gamma and GM-CSF cytoplasmic mRNA</rna> .


In contrast , IL-12 induction of IFN-gamma cytoplasmic mRNA appears to only partially depend on activation of protein kinase C .

In contrast , <protein>IL-12</protein> induction of <rna>IFN-gamma cytoplasmic mRNA</rna> appears to only partially depend on activation of <protein>protein kinase C</protein> .


Furthermore , both transforming growth factor-beta and genistein , a tyrosine kinase inhibitor , could suppress IL-2 and IL-12 signaling but CsA was generally inactive .

Furthermore , both <protein>transforming growth factor-beta</protein> and genistein , a tyrosine kinase inhibitor , could suppress <protein>IL-2</protein> and <protein>IL-12</protein> signaling but CsA was generally inactive .


It also was observed that suppression of cytokine gene expression by these agents was independent of the inhibition of proliferation .

It also was observed that suppression of <dna>cytokine gene</dna> expression by these agents was independent of the inhibition of proliferation .


In addition , IL-2 but not IL-12 induced nuclear factors NF-kappa B and AP1 , and regulation of the nuclear levels of these two DNA binding protein complexes is correlated with IFN-gamma and GM-CSF gene expression .

In addition , <protein>IL-2</protein> but not <protein>IL-12</protein> induced <protein>nuclear factors</protein> <protein>NF-kappa B</protein> and <protein>AP1</protein> , and regulation of the nuclear levels of these two <protein>DNA binding protein complexes</protein> is correlated with IFN-gamma and GM-CSF gene expression .


These data indicate that IL-2 and IL-12 may have distinct signaling pathways leading to the induction of IFN-gamma and GM-CSF gene expression , and that the NK3.3 cell line may serve as a novel model for dissecting the biochemical and molecular events involved in these pathways .

These data indicate that <protein>IL-2</protein> and <protein>IL-12</protein> may have distinct signaling pathways leading to the induction of <protein>IFN-gamma</protein> and <protein>GM-CSF</protein> gene expression , and that the <cell_line>NK3.3 cell line</cell_line> may serve as a novel model for dissecting the biochemical and molecular events involved in these pathways .


A functional T-cell receptor signaling pathway is required for p95vav activity .

A functional <protein>T-cell receptor</protein> signaling pathway is required for <protein>p95vav</protein> activity .


Stimulation of the T-cell antigen receptor ( TCR ) induces activation of multiple tyrosine kinases , resulting in phosphorylation of numerous intracellular substrates .

Stimulation of the <protein>T-cell antigen receptor</protein> ( <protein>TCR</protein> ) induces activation of multiple <protein>tyrosine kinases</protein> , resulting in phosphorylation of numerous intracellular substrates .


One substrate is p95vav , which is expressed exclusively in hematopoietic and trophoblast cells .

One substrate is <protein>p95vav</protein> , which is expressed exclusively in <cell_type>hematopoietic and trophoblast cells</cell_type> .


It contains a number of structural motifs , including Src homology 2 , Src homology 3 , and pleckstrin homology domains and a putative guanine nucleotide exchange domain .

It contains a number of <protein>structural motifs</protein> , including <protein>Src homology 2 , Src homology 3 , and pleckstrin homology domains</protein> and a <protein>putative guanine nucleotide exchange domain</protein> .


The role of p95vav in TCR -mediated signaling processes is unclear .

The role of <protein>p95vav</protein> in <protein>TCR</protein> -mediated signaling processes is unclear .


Here , we show that overexpression of p95vav alone in Jurkat T cells leads to activation of the nuclear factors , including NFAT , involved in interleukin-2 expression .

Here , we show that overexpression of <protein>p95vav</protein> alone in Jurkat <cell_type>T cells</cell_type> leads to activation of the <protein>nuclear factors</protein> , including <protein>NFAT</protein> , involved in <protein>interleukin-2</protein> expression .


Furthermore , p95vav synergizes with TCR stimulation in inducing NFAT- and interleukin-2-dependent transcription .

Furthermore , <protein>p95vav</protein> synergizes with <protein>TCR</protein> stimulation in inducing NFAT- and interleukin-2-dependent transcription .


In contrast , NFAT activation by a G-protein-coupled receptor is not modulated by p95vav overexpression , suggesting that the effect is specific to the TCR signaling pathways .

In contrast , <protein>NFAT</protein> activation by a <protein>G-protein-coupled receptor</protein> is not modulated by <protein>p95vav</protein> overexpression , suggesting that the effect is specific to the <protein>TCR</protein> signaling pathways .


Although removal of the first 67 amino acids of p95vav activates its transforming potential in NIH 3T3 cells , this region appears to be required for its function in T cells .

Although removal of the <protein>first 67 amino acids</protein> of <protein>p95vav</protein> activates its transforming potential in <cell_line>NIH 3T3 cells</cell_line> , this region appears to be required for its function in <cell_type>T cells</cell_type> .


We further demonstrate that the p95vav -induced NFAT activation is not mimicked by Ras activation , though its function is dependent upon Ras and Raf .

We further demonstrate that the <protein>p95vav</protein> -induced <protein>NFAT</protein> activation is not mimicked by <protein>Ras</protein> activation , though its function is dependent upon <protein>Ras</protein> and <protein>Raf</protein> .


Furthermore , the activating function of p95vav is blocked by FK506 , suggesting that its activity also depends on calcineurin .

Furthermore , the activating function of <protein>p95vav</protein> is blocked by FK506 , suggesting that its activity also depends on <protein>calcineurin</protein> .


To further dissect p95vav involvement in TCR signaling , we analyzed various Jurkat mutants deficient in TCR signaling function or TCR expression and showed that an intact TCR signaling pathway is required for p95vav to function .

To further dissect <protein>p95vav</protein> involvement in <protein>TCR</protein> signaling , we analyzed various <cell_line>Jurkat mutants</cell_line> deficient in <protein>TCR</protein> signaling function or <protein>TCR</protein> expression and showed that an intact <protein>TCR</protein> signaling pathway is required for <protein>p95vav</protein> to function .


However , overexpression of p95vav does not appear to influence TCR -induced protein tyrosine phosphorylation or increases in cytoplasmic free calcium .

However , overexpression of <protein>p95vav</protein> does not appear to influence <protein>TCR</protein> -induced protein tyrosine phosphorylation or increases in cytoplasmic free calcium .


Taken together , our data suggest that p95vav plays an important role at an yet unidentified proximal position in the TCR signaling cascade .

Taken together , our data suggest that <protein>p95vav</protein> plays an important role at an yet unidentified proximal position in the <protein>TCR</protein> signaling cascade .


Positive and negative regulation of granulocyte-macrophage colony-stimulating factor promoter activity by AML1-related transcription factor , PEBP2 .

Positive and negative regulation of <protein>granulocyte-macrophage colony-stimulating factor</protein> promoter activity by <protein>AML1-related transcription factor</protein> , <protein>PEBP2</protein> .


The granulocyte-macrophage colony-stimulating factor ( GM-CSF ) gene promoter contains a consensus sequence for the polyomavirus enhancer binding-protein 2 ( PEBP2 ) transcription factor , which consists of alpha and beta subunits .

The <dna>granulocyte-macrophage colony-stimulating factor ( GM-CSF ) gene promoter</dna> contains a consensus sequence for the <protein>polyomavirus enhancer binding-protein 2 ( PEBP2 ) transcription factor</protein> , which consists of <protein>alpha and beta subunits</protein> .


There are at least two genes , alpha A and alpha B , encoding the alpha subunit .

There are at least two genes , <dna>alpha A</dna> and <dna>alpha B</dna> , encoding the <protein>alpha subunit</protein> .


alpha B is the mouse homologue of human AML1 gene detected at the breakpoints of t ( 8 ; 21 ) and t ( 3 ; 21 ) myeloid leukemias .

<dna>alpha B</dna> is the <dna>mouse homologue</dna> of <dna>human AML1 gene</dna> detected at the breakpoints of t ( 8 ; 21 ) and t ( 3 ; 21 ) myeloid leukemias .


We examined alpha A1 ( an alpha A-gene product ) and alpha B1 and alpha B2 ( two alpha B-encoded isomers ) for their effects on the GM-CSF promoter .

We examined <protein>alpha A1</protein> ( an <protein>alpha A-gene product</protein> ) and <protein>alpha B1</protein> and <protein>alpha B2</protein> ( two <protein>alpha B-encoded isomers</protein> ) for their effects on the <dna>GM-CSF promoter</dna> .


PEBP2 alpha A1 , alpha B1 , and alpha B2 proteins bound the PEBP2 site within the mouse GM-CSF promoter .

<protein>PEBP2 alpha A1</protein> , <protein>alpha B1</protein> , and <protein>alpha B2 proteins</protein> bound the <dna>PEBP2 site</dna> within the <dna>mouse GM-CSF promoter</dna> .


PEBP2 alpha A1 and alpha B1 enhanced the expression of the GM-CSF promoter-driven reporter plasmid in unstimulated and 12-O-tetradecanoylphorbol 13-acetate/phytohemagglutinin-stimulated human Jurkat T cells .

<protein>PEBP2 alpha A1</protein> and <protein>alpha B1</protein> enhanced the expression of the <dna>GM-CSF promoter-driven reporter plasmid</dna> in <cell_line>unstimulated and 12-O-tetradecanoylphorbol 13-acetate/phytohemagglutinin-stimulated human Jurkat T cells</cell_line> .


In contrast , the promoter activity was suppressed by alpha B2 .

In contrast , the promoter activity was suppressed by <protein>alpha B2</protein> .


Coexpression of alpha B1 and alpha B2 showed that the promoter activity could be determined by the alpha B1 /alpha B2 ratio .

Coexpression of <protein>alpha B1</protein> and <protein>alpha B2</protein> showed that the promoter activity could be determined by the <protein>alpha B1</protein> <protein>/alpha B2</protein> ratio .


Jurkat cell extract contained PEBP2 site-binding protein ( s ) that cross-reacted with antimouse alpha A1 antibodies .

Jurkat cell extract contained <protein>PEBP2 site-binding protein</protein> ( s ) that cross-reacted with <protein>antimouse alpha A1 antibodies</protein> .


Northern blot analysis indicated the expression of human PEBP2 alpha A , alpha B ( AML1 ) , and beta genes in Jurkat cells .

Northern blot analysis indicated the expression of human <protein>PEBP2 alpha A</protein> , <dna>alpha B</dna> ( <dna>AML1</dna> ) , and <dna>beta genes</dna> in <cell_line>Jurkat cells</cell_line> .


Although further studies are required to determine the precise role of PEBP2 in the GM-CSF promoter activity , the present findings suggested the importance of the relative ratio of different PEBP2 isoforms in regulating the levels of the promoter activity .

Although further studies are required to determine the precise role of <protein>PEBP2</protein> in the <protein>GM-CSF</protein> promoter activity , the present findings suggested the importance of the relative ratio of different <protein>PEBP2 isoforms</protein> in regulating the levels of the promoter activity .


IFN-gamma priming of monocytes enhances LPS-induced TNF production by augmenting both transcription and MRNA stability .

<protein>IFN-gamma</protein> priming of <cell_type>monocytes</cell_type> enhances LPS-induced <protein>TNF</protein> production by augmenting both transcription and MRNA stability .


The induction of cytokine expression in monocytes / macrophages by bacterial endotoxin or lipopolysaccharide is a critical , highly regulated host defence response .

The induction of <protein>cytokine</protein> expression in <cell_type>monocytes</cell_type> / <cell_type>macrophages</cell_type> by <protein>bacterial endotoxin</protein> or lipopolysaccharide is a critical , highly regulated host defence response .


The augmentation of LPS responses by interferon gamma ( IFN-gamma ) , referred to as priming , is well established .

The augmentation of LPS responses by <protein>interferon gamma</protein> ( <protein>IFN-gamma</protein> ) , referred to as priming , is well established .


However , the mechanism ( s ) by which priming occurs is poorly defined .


Using tumour necrosis factor ( TNF ) induction as a model , experiments were designed to analyse in detail the priming effect on the LPS response in human monocytes .

Using <protein>tumour necrosis factor</protein> ( <protein>TNF</protein> ) induction as a model , experiments were designed to analyse in detail the priming effect on the LPS response in <cell_type>human monocytes</cell_type> .


Priming by IFN-gamma was primarily manifested at the level of TNF mRNA accumulation .

Priming by <protein>IFN-gamma</protein> was primarily manifested at the level of <rna>TNF mRNA</rna> accumulation .


IFN-gamma pre-treatment affected the magnitude rather than the sensitivity of the LPS response .

<protein>IFN-gamma</protein> pre-treatment affected the magnitude rather than the sensitivity of the LPS response .


Priming occurred after several hours of treatment , and the primed state was induced by either IFN-gamma or GM-CSF , but not M-CSF .

Priming occurred after several hours of treatment , and the primed state was induced by either <protein>IFN-gamma</protein> or <protein>GM-CSF</protein> , but not <protein>M-CSF</protein> .


Primed monocytes transcribed TNF mRNA at a higher rate than freshly isolated monocytes upon activation with LPS .

Primed <cell_type>monocytes</cell_type> transcribed <rna>TNF mRNA</rna> at a higher rate than freshly isolated <cell_type>monocytes</cell_type> upon activation with LPS .


The increased transcriptional rate correlated with a marked increase in nuclear factor-kappa B activity in these cells as determined by electrophoretic mobility shift assay using a consensus NF-kappa B oligonucleotide .

The increased transcriptional rate correlated with a marked increase in <protein>nuclear factor-kappa B</protein> activity in these cells as determined by electrophoretic mobility shift assay using a <dna>consensus NF-kappa B oligonucleotide</dna> .


An additional significant finding was than TNF mRNA induced in primed cells was much more stable than in unprimed cells ( T1/2 increased 6-8-fold ) .

An additional significant finding was than <rna>TNF mRNA</rna> induced in <cell_line>primed cells</cell_line> was much more stable than in <cell_line>unprimed cells</cell_line> ( T1/2 increased 6-8-fold ) .


Consistent with the increased mRNA stability , the duration of mRNA accumulation was longer following LPS stimulation in primed monocytes , in addition to being of greater magnitude .

Consistent with the increased <rna>mRNA</rna> stability , the duration of <rna>mRNA</rna> accumulation was longer following LPS stimulation in primed <cell_type>monocytes</cell_type> , in addition to being of greater magnitude .


Finally , primed and unprimed cells possessed a differential sensitivity to the kinase inhibitor H-89 .


H-89 substantially suppressed LPS-induced TNF mRNA accumulation in unprimed cells , but had no effect on primed monocytes following LPS stimulation .

H-89 substantially suppressed LPS-induced <rna>TNF mRNA</rna> accumulation in <cell_line>unprimed cells</cell_line> , but had no effect on <cell_line>primed monocytes</cell_line> following LPS stimulation .


( ABSTRACT TRUNCATED AT 250 WORDS )


A Myc-associated zinc finger protein binding site is one of four important functional regions in the CD4 promoter .

A <dna>Myc-associated zinc finger protein binding site</dna> is one of four important <dna>functional regions</dna> in the <dna>CD4 promoter</dna> .


The CD4 promoter plays an important role in the developmental control of CD4 transcription .

The <dna>CD4 promoter</dna> plays an important role in the developmental control of <protein>CD4</protein> transcription .


In this report , we show that the minimal CD4 promoter has four factor binding sites , each of which is required for full function .

In this report , we show that the minimal <dna>CD4 promoter</dna> has four <dna>factor binding sites</dna> , each of which is required for full function .


Using biochemical and mutagenesis analyses , we determined that multiple nuclear factors bind to these independent sites .

Using biochemical and mutagenesis analyses , we determined that multiple <protein>nuclear factors</protein> bind to these independent sites .


We determined that an initiator-like sequence present at the cap site and an Ets consensus sequence are required for full promoter function .

We determined that an <dna>initiator-like sequence</dna> present at the <dna>cap site</dna> and an <dna>Ets consensus sequence</dna> are required for full <dna>promoter</dna> function .


We also demonstrate that the Myc-associated zinc finger protein ( MAZ ) appears to be the predominant factor binding to one of these sites .

We also demonstrate that the <protein>Myc-associated zinc finger protein</protein> ( <protein>MAZ</protein> ) appears to be the <protein>predominant factor</protein> binding to one of these sites .


This last site closely resembles the ME1a1 G3AG4AG3 motif previously shown to be a critical element in the P2 promoter of the c-myc gene .

This last site closely resembles the <dna>ME1a1 G3AG4AG3 motif</dna> previously shown to be a critical element in the <dna>P2 promoter</dna> of the <dna>c-myc gene</dna> .


We therefore believe that the MAZ transcription factor is also likely to play an important role in the control of developmental expression of the CD4 gene .

We therefore believe that the <protein>MAZ transcription factor</protein> is also likely to play an important role in the control of developmental expression of the <dna>CD4 gene</dna> .


Erythropoietin stimulates transcription of the TAL1/SCL gene and phosphorylation of its protein products .

<protein>Erythropoietin</protein> stimulates transcription of the <dna>TAL1/SCL gene</dna> and phosphorylation of its <protein>protein products</protein> .


Activation of the TAL1 ( or SCL ) gene , originally identified through its involvement by a recurrent chromosomal translocation , is the most frequent molecular lesion recognized in T-cell acute lymphoblastic leukemia .

Activation of the <dna>TAL1 ( or SCL ) gene</dna> , originally identified through its involvement by a recurrent chromosomal translocation , is the most frequent molecular lesion recognized in T-cell acute lymphoblastic leukemia .


The protein products of this gene contain the basic-helix-loop-helix motif characteristic of a large family of transcription factors that bind to the canonical DNA sequence CANNTG as protein heterodimers .

The <protein>protein products</protein> of this gene contain the <protein>basic-helix-loop-helix motif</protein> characteristic of a large family of <protein>transcription factors</protein> that bind to the <dna>canonical DNA sequence CANNTG</dna> as <protein>protein heterodimers</protein> .


TAL1 expression by erythroid cells in vivo and in chemical-induced erythroleukemia cell lines in vivo suggested the gene might regulate aspects of erythroid differentiation .

<protein>TAL1</protein> expression by <cell_type>erythroid cells</cell_type> in vivo and in <cell_line>chemical-induced erythroleukemia cell lines</cell_line> in vivo suggested the gene might regulate aspects of erythroid differentiation .


Since the terminal events of erythropoiesis are controlled by the glycoprotein hormone erythropoietin ( Epo ) , we investigated whether the expression or activity of the TAL1 gene and its protein products were affected by Epo in splenic erythroblasts from mice infected with an anemia-inducing strain of Friend virus ( FVA cells ) .

Since the terminal events of erythropoiesis are controlled by the <protein>glycoprotein hormone erythropoietin</protein> ( <protein>Epo</protein> ) , we investigated whether the expression or activity of the <dna>TAL1 gene</dna> and its <protein>protein products</protein> were affected by <protein>Epo</protein> in <cell_type>splenic erythroblasts</cell_type> from mice infected with an anemia-inducing strain of Friend virus ( FVA cells ) .


Epo elicited a rapid , dose-related increase in TAL1 mRNA by increasing transcription of the gene and stabilizing one of its mRNAs .

<protein>Epo</protein> elicited a rapid , dose-related increase in <rna>TAL1 mRNA</rna> by increasing transcription of the gene and stabilizing one of its <rna>mRNAs</rna> .


An Epo -inducible TAL1 DNA binding activity was identified in FVA cell nuclear extracts that subsequently decayed despite accumulating mRNA and protein .

An <protein>Epo</protein> -inducible <protein>TAL1</protein> DNA binding activity was identified in FVA cell nuclear extracts that subsequently decayed despite accumulating <rna>mRNA</rna> and protein .


Induction of DNA binding activity was associated temporally with Epo -induced phosphorylation of nuclear TAL1 protein .

Induction of DNA binding activity was associated temporally with <protein>Epo</protein> -induced phosphorylation of <protein>nuclear TAL1 protein</protein> .


These results indicate that Epo acts at both transcriptional and posttranscriptional levels on the TAL1 locus in Friend virus-induced erythroblasts and establish a link between Epo signaling mechanisms and a member of a family of transcription factors involved in the differentiation of diverse cell lineages .

These results indicate that <protein>Epo</protein> acts at both transcriptional and posttranscriptional levels on the <protein>TAL1</protein> locus in <cell_line>Friend virus-induced erythroblasts</cell_line> and establish a link between <protein>Epo</protein> signaling mechanisms and a member of a family of <protein>transcription factors</protein> involved in the differentiation of <cell_type>diverse cell lineages</cell_type> .


Nonradioactive quantification of glucocorticoid receptor expression during differentiation of human monocytic cells ( U937 ) .

Nonradioactive quantification of <protein>glucocorticoid receptor</protein> expression during differentiation of human <cell_type>monocytic cells</cell_type> ( <cell_line>U937</cell_line> ) .


We describe a method for relative quantification of specific mRNA using a nonradioactive assay based on DNA strand competition between identical sequences of biotin- and fluorescein-labeled amplicon ( probe ) and unlabeled amplicon ( target ) during hybridization .

We describe a method for relative quantification of specific <rna>mRNA</rna> using a nonradioactive assay based on DNA strand competition between identical sequences of biotin- and fluorescein-labeled amplicon ( probe ) and unlabeled amplicon ( target ) during hybridization .


As the target quantity increased , that of the double-labeled probe decreased in accordance with the mass action law .


This technique was successfully applied to evaluate differences in glucocorticoid receptor expression in U937 cells before and after the addition of potent differentiation inducers : 12-O-tetradecanoylphorbol 13-acetate ( TPA ) and a combination of all-trans retinoic acid ( RA ) and 1 , 25-dihydroxyvitamin D2 ( VD ) .

This technique was successfully applied to evaluate differences in <protein>glucocorticoid receptor</protein> expression in <cell_line>U937 cells</cell_line> before and after the addition of potent differentiation inducers : 12-O-tetradecanoylphorbol 13-acetate ( TPA ) and a combination of all-trans retinoic acid ( RA ) and 1 , 25-dihydroxyvitamin D2 ( VD ) .


We observed that TPA treatment was associated with an increase in specific binding of [ 3H ] dexamethasone and up-regulation of GR mRNA while no enhanced GR expression was perceived with RA/VD treatment .

We observed that TPA treatment was associated with an increase in specific binding of [ 3H ] dexamethasone and up-regulation of <rna>GR mRNA</rna> while no enhanced <protein>GR</protein> expression was perceived with RA/VD treatment .


Induction of Sp1 phosphorylation and NF-kappa B-independent HIV promoter domain activity in T lymphocytes stimulated by okadaic acid .

Induction of <protein>Sp1</protein> phosphorylation and <dna>NF-kappa B-independent HIV promoter</dna> domain activity in <cell_type>T lymphocytes</cell_type> stimulated by okadaic acid .


In contrast to the purely enhancer-dependent effect of cytokines such as TNF on the activity of the HIV regulatory region ( LTR ) , we observed that okadaic acid ( OKA ) activates HIV transcription through both the enhancer , responding to the factor NF-kappa B , and the promoter domain of the LTR .

In contrast to the purely enhancer-dependent effect of <protein>cytokines</protein> such as <protein>TNF</protein> on the activity of the <dna>HIV regulatory region</dna> ( <dna>LTR</dna> ) , we observed that okadaic acid ( OKA ) activates HIV transcription through both the enhancer , responding to the factor <protein>NF-kappa B</protein> , and the <dna>promoter domain</dna> of the <dna>LTR</dna> .


The inducibility of HIV LTR-driven luciferase expression constructs in lymphoblastoid cells stimulated by OKA depended on both functional Sp1 binding elements and the ability of the TATA box to bind the protein TBP .

The inducibility of <dna>HIV LTR-driven luciferase expression constructs</dna> in <cell_type>lymphoblastoid cells</cell_type> stimulated by OKA depended on both <dna>functional Sp1 binding elements</dna> and the ability of the <dna>TATA box</dna> to bind the protein <protein>TBP</protein> .


In both transformed and normal lymphocytes , OKA stimulation induced intense phosphorylation of the constitutively expressed Sp1 protein in the nucleus , a property of OKA not shared by TNF , phorbol ester , or PHA and interleukin 2 .

In both <cell_type>transformed and normal lymphocytes</cell_type> , OKA stimulation induced intense phosphorylation of the constitutively expressed <protein>Sp1 protein</protein> in the nucleus , a property of OKA not shared by <protein>TNF</protein> , phorbol ester , or <protein>PHA</protein> and <protein>interleukin 2</protein> .


Responsiveness of LTR constructs deleted of kappa B elements to HIV Tat expression was increased upon OKA but not TNF stimulation .

Responsiveness of <dna>LTR constructs</dna> deleted of <dna>kappa B elements</dna> to <protein>HIV Tat</protein> expression was increased upon OKA but not <protein>TNF</protein> stimulation .


Our results suggest that SP1 phosphorylation induced by OKA , a selective inhibitor of the serine-threonine phosphatase PP2A , facilitates the formation of a transcription complex involving general transcription factors , HIV Tat , and Sp1 proteins .

Our results suggest that <protein>SP1</protein> phosphorylation induced by OKA , a selective inhibitor of the <protein>serine-threonine phosphatase</protein> <protein>PP2A</protein> , facilitates the formation of a <protein>transcription complex</protein> involving general <protein>transcription factors</protein> , <protein>HIV Tat</protein> , and <protein>Sp1 proteins</protein> .


The formation of this complex would increase , independently of an in synergy with NF-kappa B , the low basal activity of the HIV LTR observed in normal T lymphocytes .

The formation of this complex would increase , independently of an in synergy with <protein>NF-kappa B</protein> , the low basal activity of the <dna>HIV LTR</dna> observed in <cell_type>normal T lymphocytes</cell_type> .


The role of shared receptor motifs and common Stat proteins in the generation of cytokine pleiotropy and redundancy by IL-2 , IL-4 , IL-7 , IL-13 , and IL-15 .

The role of <protein>shared receptor motifs</protein> and <protein>common Stat proteins</protein> in the generation of <protein>cytokine</protein> pleiotropy and redundancy by <protein>IL-2</protein> , <protein>IL-4</protein> , <protein>IL-7</protein> , <protein>IL-13</protein> , and <protein>IL-15</protein> .


To understand the molecular bases for cytokine redundancy and pleiotropy , we have compared the Stat proteins activated in peripheral blood lymphocytes ( PBLs ) by cytokines with shared and distinct actions .

To understand the molecular bases for cytokine redundancy and pleiotropy , we have compared the <protein>Stat proteins</protein> activated in <cell_type>peripheral blood lymphocytes</cell_type> ( <cell_type>PBLs</cell_type> ) by <protein>cytokines</protein> with shared and distinct actions .


Interleukin-2 ( IL-2 ) rapidly activated Stat5 in fresh PBL , and Stat3 and Stat5 in preactivated PBL .

<protein>Interleukin-2</protein> ( <protein>IL-2</protein> ) rapidly activated <protein>Stat5</protein> in fresh <cell_type>PBL</cell_type> , and <protein>Stat3</protein> and <protein>Stat5</protein> in <cell_type>preactivated PBL</cell_type> .


IL-7 and IL-15 induced the same complexes as IL-2 , a feature explained by the existence of similar tyrosine-phosphorylated motifs in the cytoplasmic domains of IL-2R beta and IL-7R that can serve as docking sites for Stat proteins .

<protein>IL-7</protein> and <protein>IL-15</protein> induced the same complexes as <protein>IL-2</protein> , a feature explained by the existence of similar <protein>tyrosine-phosphorylated motifs</protein> in the <protein>cytoplasmic domains</protein> of <protein>IL-2R beta</protein> and <protein>IL-7R</protein> that can serve as docking sites for <protein>Stat proteins</protein> .


IL-13 Induced the same complexes as IL-4 , a finding explained by our studies implicating IL-4R as a shared component of the receptors .

<protein>IL-13</protein> Induced the same complexes as <protein>IL-4</protein> , a finding explained by our studies implicating <protein>IL-4R</protein> as a shared component of the <protein>receptors</protein> .


These studies demonstrate that a single cytokine can activate different combinations of Stat proteins under different physiological conditions , and also indicate two mechanisms by which distinct cytokines can activate the same Stat protein .

These studies demonstrate that a single <protein>cytokine</protein> can activate different combinations of <protein>Stat proteins</protein> under different physiological conditions , and also indicate two mechanisms by which distinct <protein>cytokines</protein> can activate the same <protein>Stat protein</protein> .


Control of I kappa B-alpha proteolysis by site-specific , signal-induced phosphorylation .

Control of <protein>I kappa B-alpha</protein> proteolysis by site-specific , signal-induced phosphorylation .


I kappa B-alpha inhibits transcription factor NF-kappa B by retaining it in the cytoplasm .

<protein>I kappa B-alpha</protein> inhibits <protein>transcription factor</protein> <protein>NF-kappa B</protein> by retaining it in the cytoplasm .


Various stimuli , typically those associated with stress or pathogens , rapidly inactivate I kappa B-alpha .

Various stimuli , typically those associated with stress or pathogens , rapidly inactivate <protein>I kappa B-alpha</protein> .


This liberates NF-kappa B to translocate to the nucleus and initiate transcription of genes important for the defense of the organism .

This liberates <protein>NF-kappa B</protein> to translocate to the nucleus and initiate transcription of <dna>genes</dna> important for the defense of the organism .


Activation of NF-kappa B correlates with phosphorylation of I kappa B-alpha and requires the proteolysis of this inhibitor .

Activation of <protein>NF-kappa B</protein> correlates with phosphorylation of <protein>I kappa B-alpha</protein> and requires the proteolysis of this inhibitor .


When either serine-32 or serine-36 of I kappa B-alpha was mutated , the protein did not undergo signal-induced phosphorylation or degradation , and NF-kappa B could not be activated .

When either serine-32 or serine-36 of <protein>I kappa B-alpha</protein> was mutated , the protein did not undergo signal-induced phosphorylation or degradation , and <protein>NF-kappa B</protein> could not be activated .


These results suggest that phosphorylation at one or both of these residues is critical for activation of NF-kappa B .

These results suggest that phosphorylation at one or both of these residues is critical for activation of <protein>NF-kappa B</protein> .


Regulation of transcription of the human erythropoietin receptor gene by proteins binding to GATA-1 and Sp1 motifs .

Regulation of transcription of the <dna>human erythropoietin receptor gene</dna> by proteins binding to <dna>GATA-1 and Sp1 motifs</dna> .


Erythropoietin ( Epo ) , the primary regulator of the production of erythroid cells , acts by binding to a cell surface receptor ( EpoR ) on erythroid progenitors .

<protein>Erythropoietin</protein> ( <protein>Epo</protein> ) , the primary regulator of the production of <cell_type>erythroid cells</cell_type> , acts by binding to a <protein>cell surface receptor</protein> ( <protein>EpoR</protein> ) on <cell_type>erythroid progenitors</cell_type> .


We used deletion analysis and transfection assays with reporter gene constructs to examine the transcription control elements in the 5 ' flanking region of the human EpoR gene .

We used deletion analysis and transfection assays with <dna>reporter gene constructs</dna> to examine the <dna>transcription control elements</dna> in the <dna>5 ' flanking region</dna> of the <dna>human EpoR gene</dna> .


In erythroid cells most of the transcription activity was contained in a 150 bp promoter fragment with binding sites for transcription factors AP2 , Sp1 and the erythroid-specific GATA-1 .

In <cell_type>erythroid cells</cell_type> most of the transcription activity was contained in a <dna>150 bp promoter</dna> fragment with <dna>binding sites</dna> for <protein>transcription factors</protein> <protein>AP2</protein> , <protein>Sp1</protein> and the <protein>erythroid-specific GATA-1</protein> .


The 150 bp hEpoR promoter exhibited high and low activity in erythroid OCIM1 and K562 cells , respectively , reflecting the high and low levels of constitutive hEpoR expression .

The <dna>150 bp hEpoR promoter</dna> exhibited high and low activity in erythroid <cell_line>OCIM1</cell_line> and <cell_line>K562 cells</cell_line> , respectively , reflecting the high and low levels of constitutive <protein>hEpoR</protein> expression .


The GATA-1 and Sp1 binding sites in this promoter lacking a TATA sequence were necessary for a high level of transcription activation .

The <dna>GATA-1 and Sp1 binding sites</dna> in this promoter lacking a <dna>TATA sequence</dna> were necessary for a high level of transcription activation .


Protein-DNA binding studies suggested that Sp1 and two other CCGCCC binding proteins from erythroid and non-erythroid cells could bind to the Sp1 binding motif .

Protein-DNA binding studies suggested that <protein>Sp1</protein> and two other <protein>CCGCCC binding proteins</protein> from <cell_type>erythroid and non-erythroid cells</cell_type> could bind to the <dna>Sp1 binding motif</dna> .


By increasing GATA-1 levels via co-transfection , we were able to transactivate the hEpoR promoter in K562 cells and non-erythroid cells , but not in the highly active OCIM1 cells , although GATA-1 mRNA levels were comparable in OCIM1 and K562 .

By increasing <protein>GATA-1</protein> levels via co-transfection , we were able to transactivate the <dna>hEpoR promoter</dna> in <cell_line>K562 cells</cell_line> and <cell_type>non-erythroid cells</cell_type> , but not in the highly active <cell_type>OCIM1 cells</cell_type> , although <rna>GATA-1 mRNA</rna> levels were comparable in <cell_line>OCIM1</cell_line> and <cell_line>K562</cell_line> .


Interestingly , when we mutated the Sp1 site , resulting in a marked decrease in hEpoR promoter activity , we could restore transactivation by increasing GATA-1 levels in OCIM1 cells .

Interestingly , when we mutated the <dna>Sp1 site</dna> , resulting in a marked decrease in <dna>hEpoR promoter</dna> activity , we could restore transactivation by increasing <protein>GATA-1</protein> levels in <cell_type>OCIM1 cells</cell_type> .


These data suggest that while GATA-1 can transactivate the EpoR promoter , the level of hEpoR gene expression does not depend on GATA-1 alone .

These data suggest that while <protein>GATA-1</protein> can transactivate the <dna>EpoR promoter</dna> , the level of <dna>hEpoR gene</dna> expression does not depend on <protein>GATA-1</protein> alone .


Rather , hEpoR transcription activity depends on coordination between Sp1 and GATA-1 with other cell-specific factors , including possibly other Sp1-like binding proteins , to provide high level , tissue-specific expression .

Rather , <protein>hEpoR</protein> transcription activity depends on coordination between <protein>Sp1</protein> and <protein>GATA-1</protein> with other <protein>cell-specific factors</protein> , including possibly other <protein>Sp1-like binding proteins</protein> , to provide high level , tissue-specific expression .


Overexpression of DR-nm23 , a protein encoded by a member of the nm23 gene family , inhibits granulocyte differentiation and induces apoptosis in 32Dc13 myeloid cells .

Overexpression of <protein>DR-nm23</protein> , a protein encoded by a member of the <dna>nm23 gene family</dna> , inhibits <cell_type>granulocyte</cell_type> differentiation and induces apoptosis in <cell_line>32Dc13 myeloid cells</cell_line> .


Chronic myelogenous leukemia evolves in two clinically distinct stages : a chronic and a blast crisis phase .


The molecular changes associated with chronic phase to blast crisis transition are largely unknown .


We have identified a cDNA clone , DR-nm23 , differentially expressed in a blast-crisis cDNA library , which has approximately 70 % sequence similarity to the putative metastatic suppressor genes , nm23-H1 and nm23-H2 .

We have identified a <dna>cDNA clone</dna> , <protein>DR-nm23</protein> , differentially expressed in a <dna>blast-crisis cDNA library ,</dna> which has approximately 70 % sequence similarity to the <dna>putative metastatic suppressor genes</dna> , <dna>nm23-H1</dna> and <dna>nm23-H2</dna> .


The deduced amino acid sequence similarity to the proteins encoded by these two latter genes is approximately 65 % and includes domains and amino acid residues ( the leucine zipper-like and the RGD domain , a serine and a histidine residue in the NH2- and in the COOH-terminal portion of the protein , respectively ) postulated to be important for nm23 function .

The deduced amino acid sequence similarity to the proteins encoded by these two latter genes is approximately 65 % and includes domains and amino acid residues ( the <protein>leucine zipper-like</protein> and the <protein>RGD domain</protein> , a serine and a histidine residue in the <protein>NH2-</protein> and in the <protein>COOH-terminal portion</protein> of the protein , respectively ) postulated to be important for <protein>nm23</protein> function .


DR-nm23 mRNA is preferentially expressed at early stages of myeloid differentiation of highly purified CD34+ cells .

<rna>DR-nm23 mRNA</rna> is preferentially expressed at early stages of myeloid differentiation of <cell_line>highly purified CD34+ cells</cell_line> .


Its constitutive expression in the myeloid precursor 32Dc13 cell line , which is growth-factor dependent for both proliferation and differentiation , results in inhibition of granulocytic differentiation induced by granulocyte colony-stimulating factor and causes apoptotic cell death .

Its constitutive expression in the <cell_line>myeloid precursor 32Dc13 cell line</cell_line> , which is growth-factor dependent for both proliferation and differentiation , results in inhibition of granulocytic differentiation induced by <protein>granulocyte colony-stimulating factor</protein> and causes apoptotic cell death .


These results are consistent with a role for DR-nm23 in normal hematopoiesis and raise the possibility that its overexpression contributes to differentiation arrest , a feature of blastic transformation in chronic myelogenous leukemia .

These results are consistent with a role for <protein>DR-nm23</protein> in normal hematopoiesis and raise the possibility that its overexpression contributes to differentiation arrest , a feature of blastic transformation in chronic myelogenous leukemia .


An interferon-gamma activation sequence mediates the transcriptional regulation of the IgG Fc receptor type IC gene by interferon-gamma .

An <dna>interferon-gamma activation sequence</dna> mediates the transcriptional regulation of the <dna>IgG Fc receptor type IC gene</dna> by <protein>interferon-gamma</protein> .


Expression of the IgG Fc receptor type I ( Fc gamma RI ) on myeloid cells is dramatically increased by treatment with interferon-gamma ( IFN-gamma ) .

Expression of the <protein>IgG Fc receptor type I</protein> ( <protein>Fc gamma RI</protein> ) on <cell_type>myeloid cells</cell_type> is dramatically increased by treatment with <protein>interferon-gamma</protein> ( <protein>IFN-gamma</protein> ) .


We observed that Fc gamma RI transcript levels in monoblast-like U937 cells were elevated within 3 hr and peaked 12 hr after exposure to IFN-gamma .

We observed that <protein>Fc gamma RI</protein> transcript levels in <cell_line>monoblast-like U937 cells</cell_line> were elevated within 3 hr and peaked 12 hr after exposure to <protein>IFN-gamma</protein> .


Treatment of U937 with IFN-gamma for 9 hr in the presence of cycloheximide led to super-induction of Fc gamma RI expression .

Treatment of <cell_line>U937</cell_line> with <protein>IFN-gamma</protein> for 9 hr in the presence of cycloheximide led to super-induction of <protein>Fc gamma RI</protein> expression .


Nuclear run-on analysis revealed that the rate of Fc gamma RI transcription was increased by IFN-gamma .

Nuclear run-on analysis revealed that the rate of <protein>Fc gamma RI</protein> transcription was increased by <protein>IFN-gamma</protein> .


Genomic sequence upstream of the Fc gamma RIC gene was cloned and subjected to primer extension analysis , which demonstrated a single transcription initiation site without a TATA box .

Genomic sequence upstream of the <dna>Fc gamma RIC gene</dna> was cloned and subjected to primer extension analysis , which demonstrated a single <dna>transcription initiation site</dna> without a <dna>TATA box</dna> .


Transient transfections of CAT reporter gene constructs containing various Fc gamma RIC promoter sequences into U937 cells revealed that a 20-bp region surrounding the transcription start site ( -7 to +13 ) was capable of mediating transcription initiation and that an IFN-gamma responsive element ( GIRE ) was present within 74 bp upstream of the transcription initiation site .

Transient transfections of <dna>CAT reporter gene constructs</dna> containing various <dna>Fc gamma RIC promoter sequences</dna> into <cell_line>U937 cells</cell_line> revealed that a <dna>20-bp region</dna> surrounding the <dna>transcription start site</dna> ( -7 to +13 ) was capable of mediating transcription initiation and that an <dna>IFN-gamma responsive element</dna> ( <dna>GIRE</dna> ) was present within <dna>74 bp upstream</dna> of the <dna>transcription initiation site</dna> .


A 17-bp sequence between positions -51 and -35 conferred IFN-gamma responsiveness on a heterologous promoter .

A <dna>17-bp sequence</dna> between positions -51 and -35 conferred <protein>IFN-gamma</protein> responsiveness on a <dna>heterologous promoter</dna> .


Double-stranded GIRE sequence , but not a scrambled sequence , was specifically bound by nuclear proteins from IFN-gamma treated U937 cells .

<dna>Double-stranded GIRE sequence</dna> , but not a <dna>scrambled sequence</dna> , was specifically bound by <protein>nuclear proteins</protein> from <cell_line>IFN-gamma treated U937 cells</cell_line> .


Gel shift experiments further showed that the STAT1 alpha protein bound to the Fc gamma RIC GIRE in response to IFN-gamma treatment of U937 cells .

Gel shift experiments further showed that the <protein>STAT1 alpha protein</protein> bound to the <dna>Fc gamma RIC GIRE</dna> in response to <protein>IFN-gamma</protein> treatment of <cell_line>U937 cells</cell_line> .


The Fc gamma RIC GIRE is homologous to the IFN-gamma activation sequence ( GAS ) of the guanylate binding protein and to X box elements of class II MHC genes .

The <dna>Fc gamma RIC GIRE</dna> is homologous to the <dna>IFN-gamma activation sequence</dna> ( <dna>GAS</dna> ) of the <protein>guanylate binding protein</protein> and to <dna>X box elements</dna> of <dna>class II MHC genes</dna> .


Our results demonstrate that transcriptional regulation of the Fc gamma RIC gene by IFN-gamma involves the binding of STAT1 alpha to a 17-bp GAS homology in the proximal promoter .

Our results demonstrate that transcriptional regulation of the <dna>Fc gamma RIC gene</dna> by <protein>IFN-gamma</protein> involves the binding of <protein>STAT1 alpha</protein> to a <dna>17-bp GAS homology</dna> in the <dna>proximal promoter</dna> .


Constitutively activated Jak -STAT pathway in T cells transformed with HTLV-I .

Constitutively activated <protein>Jak</protein> <protein>-STAT</protein> pathway in <cell_type>T cells</cell_type> transformed with HTLV-I .


Human T cell lymphotropic virus I ( HTLV-I ) is the etiological agent for adult T cell leukemia and tropical spastic paraparesis ( also termed HTLV-I-associated myelopathy ) .


HTLV-I-infected peripheral blood T cells exhibit an initial phase of interleukin-2 ( IL-2 ) -dependent growth ; over time , by an unknown mechanism , the cells become IL-2 -independent .

<cell_type>HTLV-I-infected peripheral blood T cells</cell_type> exhibit an initial phase of <protein>interleukin-2</protein> ( <protein>IL-2</protein> ) -dependent growth ; over time , by an unknown mechanism , the cells become <protein>IL-2</protein> -independent .


Whereas the Jak kinases Jak1 and Jak3 and the signal transducer and activator of transcription proteins Stat3 and Stat5 are activated in normal T cells in response to IL-2 , this signaling pathway was constitutively activated in HTLV-I-transformed cells .

Whereas the <protein>Jak kinases</protein> <protein>Jak1</protein> and <protein>Jak3</protein> and the signal transducer and activator of <protein>transcription proteins</protein> <protein>Stat3</protein> and <protein>Stat5</protein> are activated in <cell_type>normal T cells</cell_type> in response to <protein>IL-2</protein> , this signaling pathway was constitutively activated in <cell_line>HTLV-I-transformed cells</cell_line> .


In HTLV-I-infected cord blood lymphocytes , the transition from IL-2 -dependent to IL-2 -independent growth correlated with the acquisition of a constitutively activated Jak -STAT pathway , which suggests that this pathway participates in HTLV-I-mediated T cell transformation .

In <cell_line>HTLV-I-infected cord blood lymphocytes</cell_line> , the transition from <protein>IL-2</protein> -dependent to <protein>IL-2</protein> -independent growth correlated with the acquisition of a constitutively activated <protein>Jak</protein> <protein>-STAT</protein> pathway , which suggests that this pathway participates in HTLV-I-mediated T cell transformation .


Nitric oxide decreases cytokine -induced endothelial activation .

Nitric oxide decreases <protein>cytokine</protein> -induced endothelial activation .


Nitric oxide selectively reduces endothelial expression of adhesion molecules and proinflammatory cytokines .

Nitric oxide selectively reduces endothelial expression of <protein>adhesion molecules</protein> and <protein>proinflammatory cytokines</protein> .


To test the hypothesis that nitric oxide ( NO ) limits endothelial activation , we treated cytokine-stimulated human saphenous vein endothelial cells with several NO donors and assessed their effects on the inducible expression of vascular cell adhesion molecule-1 ( VCAM-1 ) .

To test the hypothesis that nitric oxide ( NO ) limits endothelial activation , we treated <cell_line>cytokine-stimulated human saphenous vein endothelial cells</cell_line> with several NO donors and assessed their effects on the inducible expression of <protein>vascular cell adhesion molecule-1</protein> ( <protein>VCAM-1</protein> ) .


In a concentration-dependent manner , NO inhibited interleukin ( IL ) -1 alpha-stimulated VCAM-1 expression by 35-55 % as determined by cell surface enzyme immunoassays and flow cytometry .

In a concentration-dependent manner , NO inhibited <protein>interleukin ( IL ) -1</protein> alpha-stimulated <protein>VCAM-1</protein> expression by 35-55 % as determined by cell surface enzyme immunoassays and flow cytometry .


This inhibition was paralleled by reduced monocyte adhesion to endothelial monolayers in nonstatic assays , was unaffected by cGMP analogues , and was quantitatively similar after stimulation by either IL-1 alpha , IL-1 beta , IL-4 , tumor necrosis factor ( TNF alpha ) , or bacterial lipopolysaccharide .

This inhibition was paralleled by reduced monocyte adhesion to endothelial monolayers in nonstatic assays , was unaffected by cGMP analogues , and was quantitatively similar after stimulation by either <protein>IL-1 alpha</protein> , <protein>IL-1 beta</protein> , <protein>IL-4</protein> , <protein>tumor necrosis factor</protein> ( <protein>TNF alpha</protein> ) , or bacterial lipopolysaccharide .


NO also decreased the endothelial expression of other leukocyte adhesion molecules ( E-selectin and to a lesser extent , intercellular adhesion molecule-1 ) and secretable cytokines ( IL-6 and IL-8 ) .

NO also decreased the endothelial expression of other <protein>leukocyte adhesion molecules</protein> ( <protein>E-selectin</protein> and to a lesser extent , <protein>intercellular adhesion molecule-1</protein> ) and secretable <protein>cytokines</protein> ( <protein>IL-6</protein> and <protein>IL-8</protein> ) .


Inhibition of endogenous NO production by L-N-monomethyl-arginine also induced the expression of VCAM-1 , but did not augment cytokine-induced VCAM-1 expression .

Inhibition of endogenous NO production by L-N-monomethyl-arginine also induced the expression of <protein>VCAM-1</protein> , but did not augment cytokine-induced <protein>VCAM-1</protein> expression .


Nuclear run-on assays , transfection studies using various VCAM-1 promoter reporter gene constructs , and electrophoretic mobility shift assays indicated that NO represses VCAM-1 gene transcription , in part , by inhibiting NF-kappa B .

Nuclear run-on assays , transfection studies using various <dna>VCAM-1 promoter reporter gene constructs</dna> , and electrophoretic mobility shift assays indicated that NO represses <protein>VCAM-1</protein> gene transcription , in part , by inhibiting <protein>NF-kappa B</protein> .


We propose that NO 's ability to limit endothelial activation and inhibit monocyte adhesion may contribute to some of its antiatherogenic and antiinflammatory properties within the vessel wall .


MIP1 alpha nuclear protein ( MNP ) , a novel transcription factor expressed in hematopoietic cells that is crucial for transcription of the human MIP-1 alpha gene .

<protein>MIP1 alpha nuclear protein</protein> ( <protein>MNP</protein> ) , a novel <protein>transcription factor</protein> expressed in hematopoietic cells that is crucial for transcription of the <dna>human MIP-1 alpha gene</dna> .


Murine macrophage inflammatory protein 1 alpha ( MIP-1 alpha ) and its human equivalent ( GOS19 , LD78 , or AT464 ) are members of the -C-C family of low-molecular-weight chemokines .

<protein>Murine macrophage inflammatory protein 1 alpha</protein> ( <protein>MIP-1 alpha</protein> ) and its <protein>human equivalent</protein> ( <protein>GOS19</protein> , <protein>LD78</protein> , or <protein>AT464</protein> ) are members of the <protein>-C-C family</protein> of <protein>low-molecular-weight chemokines</protein> .


Secreted from activated T cells and macrophages , bone marrow-derived MIP-1 alpha/GOS19 inhibits primitive hematopoietic stem cells and appears to be involved in the homeostatic control of stem cell proliferation .

Secreted from <cell_type>activated T cells</cell_type> and <cell_type>macrophages</cell_type> , bone <protein>marrow-derived MIP-1 alpha/GOS19</protein> inhibits <cell_type>primitive hematopoietic stem cells</cell_type> and appears to be involved in the homeostatic control of <cell_type>stem cell</cell_type> proliferation .


It also induces chemotaxis and inflammatory responses in mature cell types .

It also induces chemotaxis and inflammatory responses in <cell_type>mature cell types</cell_type> .


Therefore , it is important to understand the mechanisms which control the expression of MIP-1 alpha /GOS19 .

Therefore , it is important to understand the mechanisms which control the expression of <protein>MIP-1 alpha</protein> <protein>/GOS19</protein> .


Previous work has shown that in Jurkat T cells , a set of widely expressed transcription factors ( the ICK-1 family ) affect the GOS19 promoter .

Previous work has shown that in <cell_line>Jurkat T cells</cell_line> , a set of widely expressed <protein>transcription factors</protein> ( the <protein>ICK-1 family</protein> ) affect the <dna>GOS19 promoter</dna> .


One member , ICK-1A , behaves as a strong negative regulator .

One member , <protein>ICK-1A</protein> , behaves as a <protein>strong negative regulator</protein> .


In this communication , we provide evidence that the pathway of induction in the macrophage cell line U937 is different from that in Jurkat cells .

In this communication , we provide evidence that the pathway of induction in the <cell_line>macrophage cell line</cell_line> <cell_line>U937</cell_line> is different from that in <cell_line>Jurkat cells</cell_line> .


Furthermore , we show that the ICK-1 binding site does not confer negative regulation in U937 cells .

Furthermore , we show that the <dna>ICK-1 binding site</dna> does not confer negative regulation in <cell_line>U937 cells</cell_line> .


We provide evidence for an additional binding site , the MIP-1 alpha nuclear protein ( MNP ) site , which overlaps the ICK-1 site .

We provide evidence for an additional <dna>binding site</dna> , the <dna>MIP-1 alpha nuclear protein ( MNP ) site</dna> , which overlaps the <dna>ICK-1 site</dna> .


Interaction of nuclear extracts from various cell lines and tissue with the MNP site leads to the formation of fast-migrating protein-DNA complexes with similar but distinct electrophoretic mobilities .

Interaction of nuclear extracts from <cell_line>various cell lines</cell_line> and tissue with the <dna>MNP site</dna> leads to the formation of <protein>fast-migrating protein-DNA complexes</protein> with similar but distinct electrophoretic mobilities .


A mutation of the MNP site which does not abrogate ICK-1 binding inactivates the GOS19.1 promoter in U937 cells and reduces its activity by fourfold in Jurkat cells .

A mutation of the <dna>MNP site</dna> which does not abrogate ICK-1 binding inactivates the <dna>GOS19.1 promoter</dna> in <cell_line>U937 cells</cell_line> and reduces its activity by fourfold in <cell_line>Jurkat cells</cell_line> .


We propose that the MNP protein ( s ) binding at the MNP site constitutes a novel transcription factor ( s ) expressed in hematopoietic cells .

We propose that the <protein>MNP protein</protein> ( s ) binding at the <dna>MNP site</dna> constitutes a novel <protein>transcription factor</protein> ( s ) expressed in <cell_type>hematopoietic cells</cell_type> .


The effect of Toremifene on the expression of some genes in human mononuclear cells .

The effect of Toremifene on the expression of some genes in <cell_type>human mononuclear cells</cell_type> .


Toremifene exerts multiple and varied effects on the gene expression of human peripheral mononuclear cells .

Toremifene exerts multiple and varied effects on the gene expression of <cell_type>human peripheral mononuclear cells</cell_type> .


After short-term , in vitro exposure to therapeutical levels , distinct changes in P-glycoprotein , steroid receptors , p53 and Bcl-2 expression take place .


In view of the increasing use of antiestrogens in cancer therapy and prevention , there is obvious merit in long-term in vivo studies to be conducted .


The interleukin-5 /receptor interaction activates Lyn and Jak2 tyrosine kinases and propagates signals via the Ras-Raf-1-MAP kinase and the Jak -STAT pathways in eosinophils .

The <protein>interleukin-5</protein> /receptor interaction activates <protein>Lyn and Jak2 tyrosine kinases</protein> and propagates signals via the <protein>Ras-Raf-1-MAP kinase</protein> and the <protein>Jak</protein> <protein>-STAT</protein> pathways in <cell_type>eosinophils</cell_type> .


We have shown that the interaction of interleukin ( IL ) -5 with the receptor activates Lyn tyrosine kinase within 1 min and Jak2 tyrosine kinase within 1-3 min .

We have shown that the interaction of <protein>interleukin ( IL ) -5</protein> with the receptor activates <protein>Lyn tyrosine kinase</protein> within 1 min and <protein>Jak2 tyrosine kinase</protein> within 1-3 min .


IL-5 also stimulates GTP binding to p21ras .

<protein>IL-5</protein> also stimulates GTP binding to <protein>p21ras</protein> .


The signal is subsequently propagated through the activation of Raf-1 , MEK , and MAP kinases as shown by their increased autophosphorylation in vitro and phosphorylation in situ .

The signal is subsequently propagated through the activation of <protein>Raf-1</protein> , <protein>MEK</protein> , and <protein>MAP kinases</protein> as shown by their increased autophosphorylation in vitro and phosphorylation in situ .


Jak2 kinase has been shown to phosphorylate STAT nuclear proteins .

<protein>Jak2 kinase</protein> has been shown to phosphorylate <protein>STAT nuclear proteins</protein> .


The activation of STAT nuclear factors was studied by electrophoretic mobility shift assay using a gamma activation site ( GAS ) probe .

The activation of <protein>STAT nuclear factors</protein> was studied by electrophoretic mobility shift assay using a <dna>gamma activation site</dna> ( <dna>GAS</dna> ) probe .


We found that IL-5 induces two GAS-binding proteins in eosinophils , one of which is STAT1 .

We found that <protein>IL-5</protein> induces two <protein>GAS-binding proteins</protein> in <cell_type>eosinophils</cell_type> , one of which is <protein>STAT1</protein> .


We conclude that IL-5 induced signals are propagated through two distinct pathways : ( 1 ) Lyn -- > Ras -- > Raf-1 -- > MEK -- > MAP kinase and ( 2 ) Jak2 -- > STAT1 .

We conclude that <protein>IL-5</protein> induced signals are propagated through two distinct pathways : ( 1 ) <protein>Lyn</protein> -- > <protein>Ras</protein> -- > <protein>Raf-1</protein> -- > <protein>MEK</protein> -- > <protein>MAP kinase</protein> and ( 2 ) <protein>Jak2</protein> -- > <protein>STAT1</protein> .


The retinoblastoma gene product negatively regulates transcriptional activation mediated by the human cytomegalovirus IE2 protein .

The <protein>retinoblastoma gene product</protein> negatively regulates transcriptional activation mediated by the <protein>human cytomegalovirus IE2 protein</protein> .


The IE2 gene product of human cytomegalovirus ( HCMV ) is one of a few viral regulatory proteins expressed immediately upon infection of the host cell .

The <protein>IE2 gene product</protein> of human cytomegalovirus ( HCMV ) is one of a few <protein>viral regulatory proteins</protein> expressed immediately upon infection of the <cell_type>host cell</cell_type> .


It is a potent transcriptional activator of many viral and cellular promoters .

It is a potent <protein>transcriptional activator</protein> of many <dna>viral and cellular promoters</dna> .


We found that the retinoblastoma susceptibility gene product ( Rb ) dramatically suppressed this IE2 transactivation of various promoters .

We found that the <protein>retinoblastoma susceptibility gene product</protein> ( <protein>Rb</protein> ) dramatically suppressed this <protein>IE2</protein> transactivation of <dna>various promoters</dna> .


However , unlike another tumor suppressor protein , p53 , Rb did not have any significant effect on basal levels of transcription , suggesting that Rb specifically interacts with IE2 rather than other cellular factors involved in the general transcription machinery .

However , unlike another <protein>tumor suppressor protein</protein> , <protein>p53</protein> , <protein>Rb</protein> did not have any significant effect on basal levels of transcription , suggesting that <protein>Rb</protein> specifically interacts with <protein>IE2</protein> rather than other <protein>cellular factors</protein> involved in the general transcription machinery .


We found by protein-affinity chromatography that Rb in nuclear extracts or produced by in vitro translation directly bound to IE2 .

We found by protein-affinity chromatography that <protein>Rb</protein> in nuclear extracts or produced by in vitro translation directly bound to <protein>IE2</protein> .


Our results suggest that Rb may regulate the life cycle of HCMV , which is endemic in the human population .

Our results suggest that <protein>Rb</protein> may regulate the life cycle of HCMV , which is endemic in the human population .


Furthermore , these data may provide new insights into the slow rate of HCMV DNA replication in cells and the possible involvement of HCMV in tumorigenesis .


Expression of the nucleoside diphosphate kinase in human skin cancers : an immunohistochemical study .

Expression of the <protein>nucleoside diphosphate kinase</protein> in human skin cancers : an immunohistochemical study .


Expression of nucleoside diphosphate ( NDP ) kinase , which is homologous to the nm23 gene product in a variety of species , has been found to be inversely associated with metastatic potential .

Expression of <protein>nucleoside diphosphate ( NDP ) kinase</protein> , which is homologous to the <protein>nm23 gene product</protein> in a variety of species , has been found to be inversely associated with metastatic potential .


However , the relationship remains controversial according to the tumor cell types and experimental system , with conflicting results from different research groups .

However , the relationship remains controversial according to the <cell_type>tumor cell types</cell_type> and experimental system , with conflicting results from different research groups .


In order to determine whether NDP kinase expression serves as a marker for metastatic potential in human skin cancer , we assessed the levels of NDP kinase expression in 9 keratoacanthomas ( KAs ) , 26 squamous cell carcinomas ( SCCs ) , and 25 basal cell carcinomas ( BCCs ) using immunohistochemistry .

In order to determine whether <protein>NDP kinase</protein> expression serves as a marker for metastatic potential in human skin cancer , we assessed the levels of <protein>NDP kinase</protein> expression in 9 keratoacanthomas ( KAs ) , 26 squamous cell carcinomas ( SCCs ) , and 25 basal cell carcinomas ( BCCs ) using immunohistochemistry .