Analysis of RelA ( p65 ) mRNA revealed that the stability of RelA ( p65 ) mRNA was significantly higher in MDMs , compared with monocytes .

Analysis of <rna>RelA ( p65 ) mRNA</rna> revealed that the stability of <rna>RelA ( p65 ) mRNA</rna> was significantly higher in <cell_type>MDMs</cell_type> , compared with <cell_type>monocytes</cell_type> .


In MDMs , an upregulation of I kappa B alpha synthesis as well as the appearance of a novel M ( r ) 40 , 000 form of I kappa B alpha were also observed .

In <cell_type>MDMs</cell_type> , an upregulation of <protein>I kappa B alpha</protein> synthesis as well as the appearance of a novel M ( r ) 40 , 000 form of <protein>I kappa B alpha</protein> were also observed .


These results suggest that macrophage differentiation results in the expression of active p50/RelA ( p65 ) heterodimers with the capacity to activate target gene expression .

These results suggest that macrophage differentiation results in the expression of active <protein>p50/RelA ( p65 ) heterodimers</protein> with the capacity to activate target gene expression .


The parallel induction of I kappa B alpha synthesis may allow for the continuous presence of a cytoplasmic reservoir of p50/RelA ( p65 ) complexes that are readily available for inducer-mediated stimulation .

The parallel induction of <protein>I kappa B alpha</protein> synthesis may allow for the continuous presence of a cytoplasmic reservoir of <protein>p50/RelA ( p65 ) complexes</protein> that are readily available for inducer-mediated stimulation .


Nuclear Rel-A and c-Rel protein complexes are differentially distributed within human thymocytes .

<protein>Nuclear Rel-A and c-Rel protein complexes</protein> are differentially distributed within <cell_type>human thymocytes</cell_type> .


Nuclear factor-kappa B ( NF-kappa B ) /Rel proteins are inducible transcriptional regulators of numerous cellular genes .

<protein>Nuclear factor-kappa B ( NF-kappa B ) /Rel proteins</protein> are inducible <protein>transcriptional regulators</protein> of numerous <dna>cellular genes</dna> .


They are particularly abundant in lymphoid tissues and are thought to be critical for the transcription of genes involved in immune and inflammatory responses .


We have reported previously that a nuclear NF-kappa B activity was present in freshly extracted human thymocytes in the absence of in vitro treatment of these cells .

We have reported previously that a nuclear <protein>NF-kappa B</protein> activity was present in freshly extracted <cell_type>human thymocytes</cell_type> in the absence of in vitro treatment of these cells .


In the present report , we identified NF-kappa B proteins extracted from human thymocyte nuclei as being p50/p65 and p50/c-Rel complexes .

In the present report , we identified <protein>NF-kappa B proteins</protein> extracted from human thymocyte nuclei as being <protein>p50/p65 and p50/c-Rel complexes</protein> .


Immunochemical and immunofluorescent staining of thymus sections using specific Abs allowed visualization of nuclear NF-kappa B proteins in both thymocytes and nonthymocyte cells .

Immunochemical and immunofluorescent staining of thymus sections using <protein>specific Abs</protein> allowed visualization of <protein>nuclear NF-kappa B proteins</protein> in both <cell_type>thymocytes</cell_type> and <cell_type>nonthymocyte cells</cell_type> .


This detection suggested a preferential activation of p50/c-Rel in medullary thymocytes , whereas p50/p65 was present in both cortical and medullary regions of human thymus lobules .

This detection suggested a preferential activation of <protein>p50/c-Rel</protein> in <cell_type>medullary thymocytes</cell_type> , whereas <protein>p50/p65</protein> was present in both cortical and medullary regions of human thymus lobules .


However , the intensity of p65 labeling was much higher in several thymocytes from the medulla .

However , the intensity of <protein>p65</protein> labeling was much higher in several <cell_type>thymocytes</cell_type> from the medulla .


p65 , p50 , and c-Rel activities were found in both CD4- and CD8-positive thymocytes .

p65 , p50 , and c-Rel activities were found in both <cell_type>CD4- and CD8-positive thymocytes</cell_type> .


These observations suggest that p65 and c-Rel complexes play distinct roles in gene expression and that both forms of NF-kappa B play critical roles during late stages of the intrathymic maturation of T cells .

These observations suggest that <protein>p65 and c-Rel complexes</protein> play distinct roles in gene expression and that both forms of <protein>NF-kappa B</protein> play critical roles during late stages of the intrathymic maturation of <cell_type>T cells</cell_type> .


ALY , a context-dependent coactivator of LEF-1 and AML-1 , is required for TCRalpha enhancer function .

<protein>ALY</protein> , a <protein>context-dependent coactivator</protein> of <protein>LEF-1</protein> and <protein>AML-1</protein> , is required for <dna>TCRalpha enhancer</dna> function .


LEF-1 is a transcription factor that participates in the regulation of the T-cell receptor alpha ( TCR alpha ) enhancer by facilitating the assembly of multiple proteins into a higher order nucleoprotein complex .

<protein>LEF-1</protein> is a transcription factor that participates in the regulation of the <dna>T-cell receptor alpha ( TCR alpha ) enhancer</dna> by facilitating the assembly of <protein>multiple proteins</protein> into a higher order <protein>nucleoprotein complex</protein> .


The function of LEF-1 is dependent , in part , on the HMG domain that induces a sharp bend in the DNA helix , and on an activation domain that stimulates transcription only in a specific context of other enhancer-binding proteins .

The function of <protein>LEF-1</protein> is dependent , in part , on the <protein>HMG domain</protein> that induces a sharp bend in the DNA helix , and on an <protein>activation domain</protein> that stimulates transcription only in a specific context of other <protein>enhancer-binding proteins</protein> .


With the aim of gaining insight into the function of context-dependent activation domains , we cloned ALY , a novel LEF-1-interacting protein .

With the aim of gaining insight into the function of <protein>context-dependent activation domains</protein> , we cloned <protein>ALY</protein> , a novel <protein>LEF-1-interacting protein</protein> .


ALY is a ubiquitously expressed , nuclear protein that specifically associates with the activation domains of LEF-1 and AML-1 ( CBF alpha2 , PEBP2 alpha ( B ) , which is another protein component of the TCR alpha enhancer complex .

<protein>ALY</protein> is a ubiquitously expressed , nuclear protein that specifically associates with the <protein>activation domains</protein> of <protein>LEF-1</protein> and <protein>AML-1</protein> ( <protein>CBF alpha2</protein> , <protein>PEBP2 alpha</protein> ( B ) , which is another protein component of the <protein>TCR alpha enhancer complex</protein> .


In addition , ALY can increase DNA binding by both LEF-1 and AML proteins .

In addition , <protein>ALY</protein> can increase DNA binding by both <protein>LEF-1</protein> and <protein>AML proteins</protein> .


Overexpression of ALY stimulates the activity of the TCR alpha enhancer complex reconstituted in transfected nonlymphoid HeLa cells , whereas down-regulation of ALY by anti-sense oligonucleotides virtually eliminates TCR alpha enhancer activity in T cells .

Overexpression of <protein>ALY</protein> stimulates the activity of the <protein>TCR alpha enhancer complex</protein> reconstituted in <cell_line>transfected nonlymphoid HeLa cells</cell_line> , whereas down-regulation of <protein>ALY</protein> by anti-sense oligonucleotides virtually eliminates <dna>TCR alpha enhancer</dna> activity in <cell_type>T cells</cell_type> .


Similar to LEF-1 , ALY can stimulate transcription in the context of the TCR alpha enhancer but apparently not when tethered to DNA through an heterologous DNA-binding domain .

Similar to <protein>LEF-1</protein> , <protein>ALY</protein> can stimulate transcription in the context of the <dna>TCR alpha enhancer</dna> but apparently not when tethered to DNA through an <protein>heterologous DNA-binding domain</protein> .


We propose that ALY mediates context-dependent transcriptional activation by facilitating the functional collaboration of multiple proteins in the TCR alpha enhancer complex .

We propose that <protein>ALY</protein> mediates context-dependent transcriptional activation by facilitating the functional collaboration of <protein>multiple proteins</protein> in the <protein>TCR alpha enhancer complex</protein> .


AML1a but not AML1b inhibits erythroid differentiation induced by sodium butyrate and enhances the megakaryocytic differentiation of K562 leukemia cells .

<protein>AML1a</protein> but not <protein>AML1b</protein> inhibits erythroid differentiation induced by sodium butyrate and enhances the megakaryocytic differentiation of <cell_type>K562 leukemia cells</cell_type> .


AML1 may play a role in growth and differentiation of cells along erythroid and/or megakaryocytic lineages , because a significant level of the AML1 gene is expressed in these cells .

<protein>AML1</protein> may play a role in growth and differentiation of cells along <cell_type>erythroid and/or megakaryocytic lineages</cell_type> , because a significant level of the <protein>AML1</protein> gene is expressed in these cells .


We overexpressed AML1a ( without the transcription-activating domain ) and AML1b ( with the domain ) proteins in K562 leukemia cells , which can be induced to differentiate into hemoglobin-producing cells and megakaryocytes .

We overexpressed <protein>AML1a</protein> ( without the <protein>transcription-activating domain</protein> ) and <protein>AML1b</protein> ( with the domain ) proteins in <cell_type>K562 leukemia cells</cell_type> , which can be induced to differentiate into <cell_type>hemoglobin-producing cells</cell_type> and <cell_type>megakaryocytes</cell_type> .


The AML1a-transfected K562 cells had a reduced capacity to differentiate in the presence of sodium n-butyrate but not in the presence of other inducers , such as hemin , 1-beta-D-arabinofuranosylcytosine , and herbimycin A .

The <cell_line>AML1a-transfected K562 cells</cell_line> had a reduced capacity to differentiate in the presence of sodium n-butyrate but not in the presence of other inducers , such as hemin , 1-beta-D-arabinofuranosylcytosine , and herbimycin A .


The AML1 antisense oligodeoxynucleotide but not the sense oligomer recovered its differentiation-inducing capacity in the presence of butyrate .

The <protein>AML1</protein> antisense oligodeoxynucleotide but not the sense oligomer recovered its differentiation-inducing capacity in the presence of butyrate .


On the other hand , AML1b conferred a similar differentiation-inducing capacity upon K562 cells transfected with vector alone .

On the other hand , <protein>AML1b</protein> conferred a similar differentiation-inducing capacity upon <cell_line>K562 cells</cell_line> transfected with vector alone .


AML1a expression was associated with enhanced sensitivity to megakaryocytic differentiation induced by phorbol ester .

<protein>AML1a</protein> expression was associated with enhanced sensitivity to megakaryocytic differentiation induced by phorbol ester .


These results provide evidence that AML1 proteins play a role in erythroid and megakaryocytic differentiation .

These results provide evidence that <protein>AML1</protein> proteins play a role in erythroid and megakaryocytic differentiation .


Identification of sequence alterations in the upstream regulatory region of the estrogen receptor gene in an ER-negative breast cancer cell line .

Identification of sequence alterations in the <dna>upstream regulatory region</dna> of the <dna>estrogen receptor gene</dna> in an <cell_line>ER-negative breast cancer cell line</cell_line> .


Given the important role of the estrogen receptor ( ER ) in the development and physiology of the breast , it is essential to delineate the mechanisms responsible for its failed expression in some breast tumors .

Given the important role of the <protein>estrogen receptor</protein> ( <protein>ER</protein> ) in the development and physiology of the breast , it is essential to delineate the mechanisms responsible for its failed expression in some breast tumors .


We have cloned and sequenced a portion of the ER upstream regulatory region from the ER-positive MCF-7 and the ER-negative MDA-MB-231 breast cancer cell lines to determine if sequence alterations in this region account for the ER -negative phenotype of some tumors .

We have cloned and sequenced a portion of the <protein>ER</protein> <dna>upstream regulatory region</dna> from the <cell_line>ER-positive MCF-7</cell_line> and the <cell_line>ER-negative MDA-MB-231 breast cancer cell lines</cell_line> to determine if sequence alterations in this region account for the <protein>ER</protein> -negative phenotype of some tumors .


From this , we identified a number of variations between the sequences , two of which were determined to be associated with a 50 % decrease in CAT activity .

From this , we identified a number of variations between the sequences , two of which were determined to be associated with a 50 % decrease in <protein>CAT</protein> activity .


Suppression by azelastine hydrochloride of NF-kappa B activation involved in generation of cytokines and nitric oxide .

Suppression by azelastine hydrochloride of <protein>NF-kappa B</protein> activation involved in generation of <protein>cytokines</protein> and nitric oxide .


The influence of the anti-allergy agent azelastine hydrochloride ( Azeptin ) on NF-kappa B activation associated with the generation of cytokines and nitric oxide ( NO ) was investigated in various kinds of human and mouse cells .

The influence of the anti-allergy agent azelastine hydrochloride ( Azeptin ) on <protein>NF-kappa B</protein> activation associated with the generation of <protein>cytokines</protein> and nitric oxide ( NO ) was investigated in various kinds of <cell_type>human and mouse cells</cell_type> .


Azeptin dose-dependently suppressed both DNA and protein synthesis in human gingival fibroblasts ( HF ) and also suppressed blastogenesis of human peripheral blood lymphocytes ( PBL ) . Generation of tumor necrosis factor-alpha , interleukin 1-beta , granulocyte-macrophage colony-stimulating factor and interleukin-6 from 10 ( -5 ) M Azeptin-treated PBL and human monocytes ( HM ) was decreased to approximately 1/3 to 2/3 of the control levels .

Azeptin dose-dependently suppressed both DNA and protein synthesis in <cell_type>human gingival fibroblasts</cell_type> ( <cell_type>HF</cell_type> ) and also suppressed blastogenesis of <cell_type>human peripheral blood lymphocytes</cell_type> ( <cell_type>PBL</cell_type> ) . Generation of <protein>tumor necrosis factor-alpha</protein> , <protein>interleukin 1-beta</protein> , <protein>granulocyte-macrophage colony-stimulating factor</protein> and <protein>interleukin-6</protein> from 10 ( -5 ) M Azeptin-treated <cell_type>PBL</cell_type> and <cell_type>human monocytes</cell_type> ( <cell_type>HM</cell_type> ) was decreased to approximately 1/3 to 2/3 of the control levels .


In parallel with the decreased cytokine generation , each cytokine mRNA was less expressed in the presence of 10 ( -5 ) M Azeptin .

In parallel with the decreased <protein>cytokine</protein> generation , each <rna>cytokine mRNA</rna> was less expressed in the presence of 10 ( -5 ) M Azeptin .


In addition , both inducible nitric oxide synthase -mRNA level and NO generation in mouse peritoneal macrophages were suppressed by 10 ( -5 ) M Azeptin .

In addition , both inducible <protein>nitric oxide synthase</protein> -mRNA level and NO generation in <cell_type>mouse peritoneal macrophages</cell_type> were suppressed by 10 ( -5 ) M Azeptin .


Being compatible with those results , Azeptin ( 10 ( -5 ) M ) suppressed activation of NF-kappa B in PBL , HM and HF .

Being compatible with those results , Azeptin ( 10 ( -5 ) M ) suppressed activation of <protein>NF-kappa B</protein> in <cell_type>PBL</cell_type> , HM and <cell_type>HF</cell_type> .


These results appear to indicate that suppression of cytokine and NO generation by Azeptin results at least partially from the inhibition of NF-kappa B activation .

These results appear to indicate that suppression of <protein>cytokine</protein> and NO generation by Azeptin results at least partially from the inhibition of <protein>NF-kappa B</protein> activation .


Differential interaction of nuclear factors with the PRE-I enhancer element of the human IL-4 promoter in different T cell subsets .

Differential interaction of nuclear factors with the <dna>PRE-I enhancer element</dna> of the <dna>human IL-4 promoter</dna> in different <cell_type>T cell subsets</cell_type> .


The immunomodulatory cytokine IL-4 affects cells of most hemopoietic lineages .

The immunomodulatory <protein>cytokine</protein> <protein>IL-4</protein> affects cells of most <cell_type>hemopoietic lineages</cell_type> .


IL-4 is secreted by activated Th2 but not Th1 cells and plays a major role in the immune response by modulating the differentiation of naive Th cells toward the Th2 phenotype .

<protein>IL-4</protein> is secreted by activated <cell_type>Th2</cell_type> but not <cell_type>Th1 cells</cell_type> and plays a major role in the immune response by modulating the differentiation of <cell_type>naive Th cells</cell_type> toward the <cell_type>Th2 phenotype</cell_type> .


We have previously identified an enhancer element , PRE-I , that is essential for the function of the human IL-4 promoter .

We have previously identified an <dna>enhancer element</dna> , <dna>PRE-I</dna> , that is essential for the function of the <dna>human IL-4 promoter</dna> .


To investigate the mechanisms responsible for tissue-specific expression of the IL-4 gene , we analyzed nuclear factors binding to the PRE-I site and compared the binding activities of these factors to the IL-4 promoter of Th1 and Th2 cells .

To investigate the mechanisms responsible for tissue-specific expression of the <protein>IL-4</protein> gene , we analyzed <protein>nuclear factors</protein> binding to the <dna>PRE-I site</dna> and compared the binding activities of these factors to the <protein>IL-4</protein> promoter of <cell_type>Th1 and Th2 cells</cell_type> .


We show that PRE-I interacts with PMA -and PMA/ionomycin-inducible , cyclosporin A-sensitive nuclear factors .

We show that <dna>PRE-I</dna> interacts with PMA -and PMA/ionomycin-inducible , cyclosporin A-sensitive <protein>nuclear factors</protein> .


Using anti-C/EBPbeta ( NF-IL6 ) , anti-C/EBPdelta ( NF-IL6beta ) , anti-NF-ATc , anti-NF-ATp , anti-Fos , and anti-Jun Abs we demonstrate that the previously identified PRE-I binding factor POS-1 is composed of different transcription factors in different Th cell subsets .

Using <protein>anti-C/EBPbeta</protein> ( <protein>NF-IL6</protein> ) , <protein>anti-C/EBPdelta</protein> ( <protein>NF-IL6beta</protein> ) , <protein>anti-NF-ATc</protein> , <protein>anti-NF-ATp</protein> , <protein>anti-Fos</protein> , and <protein>anti-Jun Abs</protein> we demonstrate that the previously identified <protein>PRE-I binding factor</protein> <protein>POS-1</protein> is composed of different <protein>transcription factors</protein> in different Th cell subsets .


In the IL-4-producing Th0-like human Jurkat and mouse EL-4 cells , POS-1 ( designated POS-1a ) contains NF-IL6beta and Jun .

In the <cell_line>IL-4-producing Th0-like human Jurkat</cell_line> and <cell_line>mouse EL-4 cells</cell_line> , <protein>POS-1</protein> ( designated <protein>POS-1a</protein> ) contains <protein>NF-IL6beta</protein> and <protein>Jun</protein> .


In the mouse Th2 D10 cells and in the human Th2 clones , POS-1 ( designated POS-1b ) contains NF-IL6beta , Jun , and NF-ATc/p .

In the <cell_line>mouse Th2 D10 cells</cell_line> and in the <cell_line>human Th2 clones</cell_line> , <protein>POS-1</protein> ( designated <protein>POS-1b</protein> ) contains <protein>NF-IL6beta</protein> , <protein>Jun</protein> , and <protein>NF-ATc/p</protein> .


In contrast , POS-1 was not found in nuclear extracts of human Th1 clones .

In contrast , <protein>POS-1</protein> was not found in nuclear extracts of <cell_line>human Th1 clones</cell_line> .


These findings suggest that PRE-I may play a role in the differential regulation of IL-4 gene expression levels .

These findings suggest that <dna>PRE-I</dna> may play a role in the differential regulation of <dna>IL-4 gene</dna> expression levels .


Regulation of human epsilon germline transcription : role of B-cell-specific activator protein .

Regulation of human epsilon <dna>germline</dna> transcription : role of <protein>B-cell-specific activator protein</protein> .


Germline transcripts initiate from promoters upstream of the immunoglobulin switch region , and are necessary to target the appropriate switch region for recombination and switching .

<protein>Germline transcripts</protein> initiate from <dna>promoters</dna> upstream of the <dna>immunoglobulin switch region</dna> , and are necessary to target the appropriate switch region for recombination and switching .


Different cytokines activate transcription at the appropriate germline promoter .

Different <protein>cytokines</protein> activate transcription at the appropriate <dna>germline promoter</dna> .


Because binding sites for B-cell-specific activator protein ( BSAP ) are located upstream of several switch regions in the immunoglobulin heavy chain gene cluster , BSAP might play a role in the regulation of germline transcription and isotype switching .

Because <dna>binding sites</dna> for <protein>B-cell-specific activator protein</protein> ( <protein>BSAP</protein> ) are located upstream of several switch regions in the <dna>immunoglobulin heavy chain gene cluster</dna> , <protein>BSAP</protein> might play a role in the regulation of <dna>germline</dna> transcription and isotype switching .


We investigated whether BSAP plays a role in the transcriptional regulation of the epsilon germline promoter in human B cells .

We investigated whether <protein>BSAP</protein> plays a role in the transcriptional regulation of the epsilon <dna>germline promoter</dna> in <cell_type>human B cells</cell_type> .


Our results showed that BSAP plays a role in both IL-4 -dependent induction and CD40 -mediated upregulation of human epsilon germline transcription .

Our results showed that <protein>BSAP</protein> plays a role in both <protein>IL-4</protein> -dependent induction and <protein>CD40</protein> -mediated upregulation of human epsilon <dna>germline</dna> transcription .


BSAP is unique among the transcription factors that regulate epsilon germline expression , because it is B cell specific , and is at the merging point of two signalling pathways that are critical for IgE switching .

<protein>BSAP</protein> is unique among the <protein>transcription factors</protein> that regulate epsilon <dna>germline</dna> expression , because it is B cell specific , and is at the merging point of two signalling pathways that are critical for <protein>IgE</protein> switching .


Experimental expression in mice and spontaneous expression in human SLE of polyomavirus T-antigen .

Experimental expression in mice and spontaneous expression in human SLE of <protein>polyomavirus T-antigen</protein> .


A molecular basis for induction of antibodies to DNA and eukaryotic transcription factors .

A molecular basis for induction of <protein>antibodies</protein> to DNA and <protein>eukaryotic transcription factors</protein> .


We have previously demonstrated that experimental expression of the polyomavirus transcription factor T-antigen has the potential to induce anti-DNA antibodies in mice .

We have previously demonstrated that experimental expression of the <protein>polyomavirus transcription factor T-antigen</protein> has the potential to induce <protein>anti-DNA antibodies</protein> in mice .


Two sets of independent evidences are presented here that demonstrate a biological relevance for this model .


First , we describe results demonstrating that mice inoculated with T-antigen-expressing plasmids produced antibodies , not only to T-antigen and DNA , but also to the DNA-binding eukaryotic transcription factors TATA-binding protein ( TBP ) , and to the cAMP-response-element-binding protein ( CREB ) .

First , we describe results demonstrating that mice inoculated with <dna>T-antigen-expressing plasmids</dna> produced <protein>antibodies</protein> , not only to <protein>T-antigen</protein> and DNA , but also to the <protein>DNA-binding eukaryotic transcription factors</protein> <protein>TATA-binding protein</protein> ( <protein>TBP</protein> ) , and to the <protein>cAMP-response-element-binding protein</protein> ( <protein>CREB</protein> ) .


Secondly , we investigated whether polyomavirus reactivation occurs in SLE patients , and whether antibodies to T-antigen , DNA , and to TBP and CREB are linked to such events .

Secondly , we investigated whether polyomavirus reactivation occurs in SLE patients , and whether <protein>antibodies</protein> to <protein>T-antigen</protein> , DNA , and to <protein>TBP</protein> and <protein>CREB</protein> are linked to such events .


Both within and among these SLE patients , frequent polyomavirus reactivations were observed that could not be explained by certain rearrangements of the noncoding control regions , nor by corticosteroid treatment .


Linked to these events , antibodies to T-antigen , DNA , TBP , and CREB were detected , identical to what we observed in mice .

Linked to these events , <protein>antibodies</protein> to <protein>T-antigen</protein> , DNA , <protein>TBP</protein> , and <protein>CREB</protein> were detected , identical to what we observed in mice .


Antibodies recognizing double-stranded DNA were confined to patients with frequent polyomavirus reactivations .


The results described here indicate that cognate interaction of B cells recognizing DNA or DNA-associated proteins and T cells recognizing T antigen had taken place as a consequence of complex formation between T ag and DNA in vivo in the context of polyomavirus reactivations .

The results described here indicate that cognate interaction of B cells recognizing DNA or <protein>DNA-associated proteins</protein> and <cell_type>T cells</cell_type> recognizing <protein>T antigen</protein> had taken place as a consequence of complex formation between <protein>T ag</protein> and DNA in vivo in the context of polyomavirus reactivations .


Jak3 is associated with CD40 and is critical for CD40 induction of gene expression in B cells .

<protein>Jak3</protein> is associated with <protein>CD40</protein> and is critical for <protein>CD40</protein> induction of gene expression in <cell_type>B cells</cell_type> .


CD40 is a receptor that is critical for the survival , growth , differentiation , and isotype switching of B lymphocytes .

<protein>CD40</protein> is a receptor that is critical for the survival , growth , differentiation , and isotype switching of <cell_type>B lymphocytes</cell_type> .


Although CD40 lacks intrinsic tyrosine kinase activity , its ligation induces protein tyrosine phosphorylation , which is necessary for several CD40 -mediated events .

Although <protein>CD40</protein> lacks intrinsic tyrosine kinase activity , its ligation induces protein tyrosine phosphorylation , which is necessary for several <protein>CD40</protein> -mediated events .


We show that engagement of CD40 induces tyrosine phosphorylation and activation of Jak3 as well as of STAT3 .

We show that engagement of <protein>CD40</protein> induces tyrosine phosphorylation and activation of <protein>Jak3</protein> as well as of <protein>STAT3</protein> .


Jak3 is constitutively associated with CD40 , and this interaction requires a proline-rich sequence in the membrane-proximal region of CD40 .

<protein>Jak3</protein> is constitutively associated with <protein>CD40</protein> , and this interaction requires a <protein>proline-rich sequence</protein> in the <protein>membrane-proximal region</protein> of <protein>CD40</protein> .


Deletion of this sequence abolishes the capacity of CD40 to induce expression of CD23 , ICAM-1 , and lymphotoxin-alpha genes in B cells .

Deletion of this sequence abolishes the capacity of <protein>CD40</protein> to induce expression of <protein>CD23</protein> , <protein>ICAM-1</protein> , and <dna>lymphotoxin-alpha genes</dna> in <cell_type>B cells</cell_type> .


These results indicate that signaling through Jak3 is activated by CD40 and plays an important role in CD40 -mediated functions .

These results indicate that signaling through <protein>Jak3</protein> is activated by <protein>CD40</protein> and plays an important role in <protein>CD40</protein> -mediated functions .


Transcription factors required for lymphoid lineage commitment .

<protein>Transcription factors</protein> required for lymphoid lineage commitment .


Intimate interactions between multipotential hemopoietic stem cells and their microenvironment work towards redefining the identity and the differentiative fate of these primitive cells .

Intimate interactions between multipotential <cell_type>hemopoietic stem cells</cell_type> and their microenvironment work towards redefining the identity and the differentiative fate of these <cell_type>primitive cells</cell_type> .


Molecular cues delivered by the microenvironment frequently act in an instructive fashion by initiating intracellular signaling pathways that ultimately target a select group of transcription factors .

Molecular cues delivered by the microenvironment frequently act in an instructive fashion by initiating intracellular signaling pathways that ultimately target a select group of <protein>transcription factors</protein> .


These transcriptional regulators in turn trigger a cascade of genetic changes that ultimately determine the course of the cells during differentiation .


Gene inactivation studies on the PU.1 , Ikaros and GATA-3 genes have revealed that their encoded factors are essential for the earliest commitment step into the B and T lymphoid lineages .

Gene inactivation studies on the <dna>PU.1 , Ikaros and GATA-3 genes</dna> have revealed that their encoded factors are essential for the earliest commitment step into the <cell_type>B and T lymphoid lineages</cell_type> .


Interleukin-4 signaling in B lymphocytes from patients with X-linked severe combined immunodeficiency .

<protein>Interleukin-4</protein> signaling in <cell_type>B lymphocytes</cell_type> from patients with X-linked severe combined immunodeficiency .


Interleukin-4 ( IL-4 ) is an important cytokine for B and T lymphocyte function and mediates its effects via a receptor that contains gammac .

<protein>Interleukin-4</protein> ( <protein>IL-4</protein> ) is an important cytokine for B and T lymphocyte function and mediates its effects via a receptor that contains <protein>gammac</protein> .


B cells derived from patients with X-linked severe combined immunodeficiency ( X-SCID ) are deficient in gammac and provide a useful model in which to dissect the role of this subunit in IL-4 -mediated signaling .

<cell_type>B cells</cell_type> derived from patients with X-linked severe combined immunodeficiency ( X-SCID ) are deficient in gammac and provide a useful model in which to dissect the role of this subunit in <protein>IL-4</protein> -mediated signaling .


We found that although IL-4 stimulation of X-SCID B cells did not result in Janus tyrosine kinase-3 ( JAK3 ) phosphorylation , other IL-4 substrates including JAK1 and IRS-1 were phosphorylated .

We found that although <protein>IL-4</protein> stimulation of <cell_type>X-SCID B cells</cell_type> did not result in <protein>Janus tyrosine kinase-3</protein> ( <protein>JAK3</protein> ) phosphorylation , other <protein>IL-4 substrates</protein> including <protein>JAK1</protein> and <protein>IRS-1</protein> were phosphorylated .


Additionally , we detected signal transducers and activators of transcription 6 ( STAT6 ) tyrosine phosphorylation and DNA binding activity in X-SCID B cells with a wide range of gammac mutations .

Additionally , we detected <protein>signal transducers and activators of transcription 6</protein> ( <protein>STAT6</protein> ) tyrosine phosphorylation and DNA binding activity in <cell_type>X-SCID B cells</cell_type> with a wide range of <protein>gammac</protein> mutations .


However , reconstitution of these X-SCID B cells with gammac enhanced IL-4 -mediated responses including STAT6 phosphorylation and DNA binding activity and resulted in increased CD23 expression .

However , reconstitution of these <cell_type>X-SCID B cells</cell_type> with <protein>gammac</protein> enhanced <protein>IL-4</protein> -mediated responses including <protein>STAT6</protein> phosphorylation and DNA binding activity and resulted in increased <protein>CD23</protein> expression .


Thus , gammac is not necessary to trigger IL-4 -mediated responses in B cells , but its presence is important for optimal IL-4 -signaling .

Thus , <protein>gammac</protein> is not necessary to trigger <protein>IL-4</protein> -mediated responses in <cell_type>B cells</cell_type> , but its presence is important for optimal <protein>IL-4</protein> -signaling .


These results suggest that two distinct IL-4 signaling pathways exist .

These results suggest that two distinct <protein>IL-4</protein> signaling pathways exist .


Cell-to-cell contact activates the long terminal repeat of human immunodeficiency virus 1 through its kappaB motif .

Cell-to-cell contact activates the <dna>long terminal repeat</dna> of human immunodeficiency virus 1 through its <dna>kappaB motif</dna> .


Cell-to-cell contact between peripheral blood lymphocytes and transfected human colonic carcinoma cell line HT29 activates transcription of the long terminal repeats ( LTR ) of human immunodeficiency virus .

Cell-to-cell contact between <cell_type>peripheral blood lymphocytes</cell_type> and <cell_line>transfected human colonic carcinoma cell line HT29</cell_line> activates transcription of the <dna>long terminal repeats</dna> ( <dna>LTR</dna> ) of human immunodeficiency virus .


HIV-1 LTR transcription is controlled by a complex array of virus-encoded and cellular proteins .

<dna>HIV-1 LTR</dna> transcription is controlled by a complex array of <protein>virus-encoded and cellular proteins</protein> .


Using various constructs expressing a lacZ reporter gene under the control of the intact or three deleted forms of HIV-1 LTR , we obtained evidence that the kappaB regulatory elements located in the U3 region are involved in cell-to-cell activation of HIV-1 LTR .

Using various constructs expressing a <dna>lacZ reporter gene</dna> under the control of the intact or three deleted forms of <dna>HIV-1 LTR</dna> , we obtained evidence that the <dna>kappaB regulatory elements</dna> located in the <dna>U3 region</dna> are involved in cell-to-cell activation of <dna>HIV-1 LTR</dna> .


Cell-to-cell contact activates in vitro binding of the nuclear factor kappaB ( NF-kappaB ) p50/p65 heterodimer to an HIV-1 kappaB oligonucleotide .

Cell-to-cell contact activates in vitro binding of the <protein>nuclear factor kappaB ( NF-kappaB ) p50/p65 heterodimer</protein> to an HIV-1 kappaB oligonucleotide .


Cell-to-cell contact activation of NF-kappaB was only partially inhibited by 100 microM pyrrolidine dithiocarbamate and was not correlated with a significant decrease of cellular inhibitor kappaB alpha .

Cell-to-cell contact activation of <protein>NF-kappaB</protein> was only partially inhibited by 100 microM pyrrolidine dithiocarbamate and was not correlated with a significant decrease of <protein>cellular inhibitor kappaB alpha</protein> .


NF-kappaB nuclear activation was not detectable before 1 h after cell contact and was dependent on protein synthesis .

<protein>NF-kappaB</protein> nuclear activation was not detectable before 1 h after cell contact and was dependent on protein synthesis .


Identification of nucleotide sequences that regulate transcription of the MCF13 murine leukemia virus long terminal repeat in activated T cells .

Identification of <dna>nucleotide sequences</dna> that regulate transcription of the MCF13 murine leukemia virus <dna>long terminal repeat</dna> in activated <cell_type>T cells</cell_type> .


The region downstream of the enhancer ( DEN ) of the long terminal repeat of the mink cell focus-forming murine leukemia virus is important for viral pathogenicity .

The region downstream of the <dna>enhancer</dna> ( <dna>DEN</dna> ) of the <dna>long terminal repeat</dna> of the mink cell focus-forming murine leukemia virus is important for viral pathogenicity .


Another important activity of DEN is its control of transcription in activated T cells , and we have determined that an NF-kappaB site is critical for this activity .

Another important activity of <dna>DEN</dna> is its control of transcription in <cell_type>activated T cells</cell_type> , and we have determined that an <protein>NF-kappaB</protein> site is critical for this activity .


Possible role of nuclear factor-kappa B activity in germline C epsilon transcription in a human Burkitt lymphoma B cell line .

Possible role of <protein>nuclear factor-kappa B</protein> activity in <dna>germline</dna> C epsilon transcription in a <cell_line>human Burkitt lymphoma B cell line</cell_line> .


Nuclear factor-kappa B ( NF-kappa B ) plays a broad role in gene regulation , but it is not evident whether NF-kappa B acts as a messenger system for germline C epsilon transcription .

<protein>Nuclear factor-kappa B</protein> ( <protein>NF-kappa B</protein> ) plays a broad role in gene regulation , but it is not evident whether <protein>NF-kappa B</protein> acts as a messenger system for <dna>germline</dna> C epsilon transcription .


We report here that the signaling cascade triggered by interleukin-4 ( IL-4 ) or anti-CD40 monoclonal antibody ( mAb ) participates in NF-kappa B activation responsible for germline C epsilon transcription in a human Burkitt lymphoma B cell line , DND39 .

We report here that the signaling cascade triggered by <protein>interleukin-4</protein> ( <protein>IL-4</protein> ) or <protein>anti-CD40 monoclonal antibody</protein> ( <protein>mAb</protein> ) participates in <protein>NF-kappa B</protein> activation responsible for <dna>germline</dna> C epsilon transcription in a <cell_line>human Burkitt lymphoma B cell line</cell_line> , <cell_line>DND39</cell_line> .


Both IL-4 and anti- CD40 mAb induced activation of phosphatidylinositol 3-kinase ( PI3-kinase ) , translocation of a zeta isoform of protein kinase C , and nuclear expression of NF-kappa B .

Both <protein>IL-4</protein> and anti- <protein>CD40 mAb</protein> induced activation of <protein>phosphatidylinositol 3-kinase</protein> ( <protein>PI3-kinase</protein> ) , translocation of a zeta isoform of <protein>protein kinase C</protein> , and nuclear expression of <protein>NF-kappa B</protein> .


All such events were abrogated by treatment with LY294002 , a specific inhibitor of PI3-kinase .

All such events were abrogated by treatment with LY294002 , a specific inhibitor of <protein>PI3-kinase</protein> .


In addition , N-acetyl-L-cysteine ( NAC ) , a potent antioxidant , decreased NF-kappa B activation caused by IL-4 , anti-CD40 mAb , or their combination .

In addition , N-acetyl-L-cysteine ( NAC ) , a potent antioxidant , decreased <protein>NF-kappa B</protein> activation caused by <protein>IL-4</protein> , <protein>anti-CD40 mAb</protein> , or their combination .


NAC was also effective in diminishing germline C epsilon transcription , and its potency was higher in cultures costimulated with IL-4 and anti-CD40 mAb than in those stimulated with IL-4 alone .

NAC was also effective in diminishing <dna>germline</dna> C epsilon transcription , and its potency was higher in cultures costimulated with <protein>IL-4</protein> and <protein>anti-CD40 mAb</protein> than in those stimulated with <protein>IL-4</protein> alone .


These results indicate that IL-4 and ligation of CD40 induce NF-kappa B expression via at least a mechanism dependent on the PI3-kinase pathway and suggest that NF-kappa B sensitive to NAC may play a role in regulating germline C epsilon transcription .

These results indicate that <protein>IL-4</protein> and ligation of <protein>CD40</protein> induce <protein>NF-kappa B</protein> expression via at least a mechanism dependent on the <protein>PI3-kinase</protein> pathway and suggest that <protein>NF-kappa B</protein> sensitive to NAC may play a role in regulating <dna>germline</dna> C epsilon transcription .


Differentiation of U-937 promonocytic cells by etoposide and ICRF-193 , two antitumour DNA topoisomerase II inhibitors with different mechanisms of action .

Differentiation of <cell_line>U-937 promonocytic cells</cell_line> by etoposide and ICRF-193 , two antitumour <protein>DNA topoisomerase II</protein> inhibitors with different mechanisms of action .


We have compared the action on U-937 human promonocytic leukemia cells of two DNA topoisomerase II inhibitors , namely the epipodophyllotoxin etoposide and the bisdioxopiperazine ICRF-193 .

We have compared the action on <cell_line>U-937 human promonocytic leukemia cells</cell_line> of two <protein>DNA topoisomerase II</protein> inhibitors , namely the epipodophyllotoxin etoposide and the bisdioxopiperazine ICRF-193 .


One hour pulse-treatment with 3 microM etoposide caused topoisomerase associated , primary DNA breakage , which was rapidly followed by apoptosis .

One hour pulse-treatment with 3 microM etoposide caused <protein>topoisomerase</protein> associated , primary DNA breakage , which was rapidly followed by apoptosis .


By contrast , these effects were not observed upon pulse-treatment with 6 microM ICRF-193 .


However , continuous treatments with subcytotoxic concentrations of etoposide ( 0.15 microM ) and ICRF-193 ( 0.3 microM ) produced several similar effects , namely decreased cell proliferation , accumulation of cells at G2 , increase in cell mass , and induction of differentiation .


Under these conditions , etoposide produced a biphasic activation of protein kinase C , which consisted in an early transient activation ( from hours 1 to 6 ) of the membrane-bound enzyme followed by a later activation ( hour 48 ) of the total , membrane-bound and cytosolic enzyme .

Under these conditions , etoposide produced a biphasic activation of <protein>protein kinase C</protein> , which consisted in an early transient activation ( from hours 1 to 6 ) of the <protein>membrane-bound enzyme</protein> followed by a later activation ( hour 48 ) of the total , <protein>membrane-bound and cytosolic enzyme</protein> .


By contrast , ICRF-193 only provoked a late activation ( from hours 72 to 96 ) of the total enzyme .


When used at differentiation-inducing concentrations , both topoisomerase inhibitors caused a great stimulation of AP-1 binding activity , with maximum value at hour 12 in etoposide-treated cells and at hour 48 in ICRF-193-treated cells .

When used at differentiation-inducing concentrations , both <protein>topoisomerase</protein> inhibitors caused a great stimulation of <protein>AP-1</protein> binding activity , with maximum value at hour 12 in etoposide-treated cells and at hour 48 in <cell_type>ICRF-193-treated cells</cell_type> .


By contrast , the binding activity of the NF-kappa ( B ) and EGR-1 transcription factors was little affected .

By contrast , the binding activity of the <protein>NF-kappa ( B )</protein> and <protein>EGR-1</protein> <protein>transcription factors</protein> was little affected .


It is concluded that topoisomerase II inhibitors may induce the differentiation of promonocytic cells , independently of their capacity to cause DNA strand breaks .


However , there are other effects , such as the early activation of protein kinase C , which are probably derived from the production of primary DNA breakage by some anti- topoisomerase drugs .

However , there are other effects , such as the early activation of <protein>protein kinase C</protein> , which are probably derived from the production of primary DNA breakage by some anti- <protein>topoisomerase</protein> drugs .


GATA-1 DNA binding activity is down-regulated in late S phase in erythroid cells .

<protein>GATA-1</protein> DNA binding activity is down-regulated in late S phase in <cell_type>erythroid cells</cell_type> .


We have set out to test a model for tissue-specific gene expression that relies on the early replication of expressed genes to sequester limiting activating transcription factors .

We have set out to test a model for tissue-specific gene expression that relies on the early replication of expressed genes to sequester limiting activating <protein>transcription factors</protein> .


Using an erythroid cell line , we have tested the changes in the DNA binding activity of the lineage-restricted transcription factor GATA-1 through the cell cycle .

Using an <cell_line>erythroid cell line</cell_line> , we have tested the changes in the DNA binding activity of the <protein>lineage-restricted transcription factor</protein> <protein>GATA-1</protein> through the cell cycle .


We find that GATA-1 activity is low in G1 , peaks in mid-S phase , and then decreases in G2/M .

We find that <protein>GATA-1</protein> activity is low in G1 , peaks in mid-S phase , and then decreases in G2/M .


In contrast , the binding activities of two ubiquitous transcription factors , Oct1 and Sp1 , remain high in G2/M .

In contrast , the binding activities of two ubiquitous <protein>transcription factors</protein> , <protein>Oct1</protein> and <protein>Sp1</protein> , remain high in G2/M .


GATA-1 protein and mRNA vary in a similar manner through the cell cycle , suggesting that the expression of the gene or the stability of its message is regulated .

<protein>GATA-1</protein> protein and <rna>mRNA</rna> vary in a similar manner through the cell cycle , suggesting that the expression of the gene or the stability of its message is regulated .


Although a number of transcription factors involved in the control of the cell cycle or DNA replication have been shown to peak in S phase , this is the first example of a lineage-restricted transcription factor displaying S phase-specific DNA binding activity .

Although a number of <protein>transcription factors</protein> involved in the control of the cell cycle or DNA replication have been shown to peak in S phase , this is the first example of a <protein>lineage-restricted transcription factor</protein> displaying S phase-specific DNA binding activity .


One interpretation of these data leads to a model in which the peak in GATA-1 DNA binding amplifies the effect of early replication on the activation of erythroid-specific genes at the same time as preventing activation of non-erythroid genes containing GATA-responsive elements .

One interpretation of these data leads to a model in which the peak in <protein>GATA-1</protein> DNA binding amplifies the effect of early replication on the activation of <dna>erythroid-specific genes</dna> at the same time as preventing activation of <dna>non-erythroid genes</dna> containing <dna>GATA-responsive elements</dna> .


These results may also relate to recent data implicating GATA-1 function in apoptosis and cell cycle progression

These results may also relate to recent data implicating <protein>GATA-1</protein> function in apoptosis and cell cycle progression


Activation of the NF-kappaB pathway by inflammatory stimuli in human neutrophils .

Activation of the <protein>NF-kappaB</protein> pathway by inflammatory stimuli in <cell_type>human neutrophils</cell_type> .


Activated neutrophils have the ability to upregulate the expression of many genes , in particular those encoding cytokines and chemokines , and to subsequently release the corresponding proteins .

<cell_type>Activated neutrophils</cell_type> have the ability to upregulate the expression of many genes , in particular those encoding <protein>cytokines</protein> and <protein>chemokines</protein> , and to subsequently release the corresponding proteins .


Although little is known to date concerning the regulation of gene transcription in neutrophils , it is noteworthy that many of these genes depend on the activation of transcription factors , such as NF-kappaB , for inducible expression .

Although little is known to date concerning the regulation of gene transcription in <cell_type>neutrophils</cell_type> , it is noteworthy that many of these genes depend on the activation of <protein>transcription factors</protein> , such as <protein>NF-kappaB</protein> , for inducible expression .


We therefore investigated whether NF-kappaB/Rel proteins are expressed in human neutrophils , as well as their fate on cell activation .

We therefore investigated whether <protein>NF-kappaB/Rel proteins</protein> are expressed in <cell_type>human neutrophils</cell_type> , as well as their fate on cell activation .


We now report that dimers consisting of p50 NFkappaB1 , p65 RelA , and/or c-Rel are present in neutrophils and that the greater part of these protein complexes is physically associated with cytoplasmic IkappaB-alpha in resting cells .

We now report that dimers consisting of <protein>p50 NFkappaB1</protein> , <protein>p65 RelA</protein> , and/or <protein>c-Rel</protein> are present in <cell_type>neutrophils</cell_type> and that the greater part of these <protein>protein complexes</protein> is physically associated with <protein>cytoplasmic IkappaB-alpha</protein> in resting cells .


Following neutrophil stimulation with proinflammatory agonists ( such as lipopolysaccharide [ LPS ] , tumor necrosis factor-alpha [ TNF-alpha ] , and fMet-Leu-Phe ) that induce the production of cytokines and chemokines in these cells , NF-kappaB/Rel proteins translocated to nuclear fractions , resulting in a transient induction of NF-kappaB DNA binding activity , as determined in gel mobility shift assays .

Following neutrophil stimulation with proinflammatory agonists ( such as lipopolysaccharide [ LPS ] , <protein>tumor necrosis factor-alpha</protein> [ <protein>TNF-alpha</protein> ] , and fMet-Leu-Phe ) that induce the production of <protein>cytokines</protein> and <protein>chemokines</protein> in these cells , <protein>NF-kappaB/Rel proteins</protein> translocated to nuclear fractions , resulting in a transient induction of <protein>NF-kappaB</protein> DNA binding activity , as determined in gel mobility shift assays .


The onset of both processes was found to be closely paralleled by , and dependent on , IkappaB-alpha degradation .

The onset of both processes was found to be closely paralleled by , and dependent on , <protein>IkappaB-alpha</protein> degradation .


Proinflammatory neutrophil stimuli also promoted the accumulation of IkappaB-alpha mRNA transcripts , resulting in the reexpression of the IkappaB-alpha protein .

<cell_type>Proinflammatory neutrophil</cell_type> stimuli also promoted the accumulation of <rna>IkappaB-alpha mRNA transcripts</rna> , resulting in the reexpression of the <protein>IkappaB-alpha protein</protein> .


To our knowledge , this constitutes the first indication that NF-kappaB activation may underlie the action of proinflammatory stimuli towards human neutrophil gene expression and , as such , adds a new facet to our understanding of neutrophil biology .

To our knowledge , this constitutes the first indication that <protein>NF-kappaB</protein> activation may underlie the action of proinflammatory stimuli towards human neutrophil gene expression and , as such , adds a new facet to our understanding of <cell_type>neutrophil biology</cell_type> .


Two distinct pathways of interleukin-5 synthesis in allergen-specific human T-cell clones are suppressed by glucocorticoids .

Two distinct pathways of <protein>interleukin-5</protein> synthesis in <cell_line>allergen-specific human T-cell clones</cell_line> are suppressed by glucocorticoids .


Glucocorticoids ( GC ) have long been used as the most effective agents for the treatment of allergic diseases accompanied by eosinophilia such as chronic asthma and atopic dermatitis .


The development of chronic eosinophilic inflammation is dependent on interleukin-5 ( IL-5 ) , a selective eosinophil-activating factor , produced by helper T cells .

The development of chronic eosinophilic inflammation is dependent on <protein>interleukin-5</protein> ( <protein>IL-5</protein> ) , a <protein>selective eosinophil-activating factor</protein> , produced by <cell_type>helper T cells</cell_type> .


To delineate the regulatory mechanisms of human IL-5 synthesis , we established allergen-specific CD4+ T-cell clones from asthmatic patients .

To delineate the regulatory mechanisms of human <protein>IL-5</protein> synthesis , we established <cell_line>allergen-specific CD4+ T-cell clones</cell_line> from asthmatic patients .


GC efficiently suppressed IL-5 synthesis of T-cell clones activated via either T-cell receptor ( TCR ) or IL-2 receptor ( IL-2R ) .

GC efficiently suppressed <protein>IL-5</protein> synthesis of T-cell clones activated via either <protein>T-cell receptor</protein> ( <protein>TCR</protein> ) or <protein>IL-2 receptor</protein> ( <protein>IL-2R</protein> ) .


Induction of IL-5 mRNA upon TCR and IL-2R stimulation was totally inhibited by dexamethasone .

Induction of <rna>IL-5 mRNA</rna> upon <protein>TCR</protein> and <protein>IL-2R</protein> stimulation was totally inhibited by dexamethasone .


Human IL-5 promoter/enhancer-luciferase gene construct transfected to T-cell clones was transcribed on either TCR or IL-2R stimulation and was clearly downregulated by dexamethasone , indicating that the approximately 500-bp human IL-5 gene segment located 5 ' upstream of the coding region contains activation-inducible enhancer elements responsible for the regulation by GC .

Human <protein>IL-5</protein> promoter/enhancer-luciferase gene construct transfected to <cell_line>T-cell clones</cell_line> was transcribed on either <protein>TCR</protein> or <protein>IL-2R</protein> stimulation and was clearly downregulated by dexamethasone , indicating that the approximately <dna>500-bp human IL-5 gene segment</dna> located <dna>5 ' upstream</dna> of the coding region contains <dna>activation-inducible enhancer elements</dna> responsible for the regulation by GC .


Electrophoretic mobility shift assay analysis suggested that AP-1 and NF-kappaB are among the possible targets of GC actions on TCR-stimulated T cells .

Electrophoretic mobility shift assay analysis suggested that <protein>AP-1</protein> and <protein>NF-kappaB</protein> are among the possible targets of GC actions on <cell_type>TCR-stimulated T cells</cell_type> .


NF-AT and NF-kappaB were not significantly induced by IL-2 stimulation .

<protein>NF-AT</protein> and <protein>NF-kappaB</protein> were not significantly induced by <protein>IL-2</protein> stimulation .


Our results showing that GC suppressed IL-5 production by human CD4+ T cells activated by two distinct stimuli , TCR and IL-2R stimulation , underscore the efficacy of GC in the treatment of allergic diseases via suppression of T-cell IL-5 synthesis .

Our results showing that GC suppressed <protein>IL-5</protein> production by <cell_type>human CD4+ T cells</cell_type> activated by two distinct stimuli , <protein>TCR</protein> and <protein>IL-2R</protein> stimulation , underscore the efficacy of GC in the treatment of allergic diseases via suppression of T-cell <protein>IL-5</protein> synthesis .


Itk , a T cell-specific tyrosine kinase , is required for CD2-mediated interleukin-2 promoter activation in the human T cell line Jurkat .

<protein>Itk</protein> , a <protein>T cell-specific tyrosine kinase</protein> , is required for <dna>CD2-mediated interleukin-2 promoter</dna> activation in the <cell_line>human T cell line Jurkat</cell_line> .


We investigated the functional role of Itk , a member of the cytoplasmic tyrosine kinase Tec family , in T cell activation .

We investigated the functional role of <protein>Itk</protein> , a member of the <protein>cytoplasmic tyrosine kinase Tec family</protein> , in T cell activation .


Stimulation of either CD2 or T cell receptor ( TCR ) /CD3 on Tcells by monoclonal antibody-mediated cross-linking induced tyrosine phosphorylation of Itk , which was maximal as early as 1 min after stimulation .

Stimulation of either <protein>CD2</protein> or T cell receptor ( <protein>TCR</protein> ) /CD3 on Tcells by monoclonal antibody-mediated cross-linking induced tyrosine phosphorylation of <protein>Itk</protein> , which was maximal as early as 1 min after stimulation .


The tyrosine kinase activity in the anti- Itk immunoprecipitate was significantly activated upon these stimulations .

The tyrosine kinase activity in the anti- <protein>Itk</protein> immunoprecipitate was significantly activated upon these stimulations .


Interleukin-2 ( IL-2 ) promoter activity stimulated by cross-linking of CD2 , TCR /CD3 , and CD28 with antibodies was significantly reduced by transient expression of an Itk mutant lacking the kinase activity .

Interleukin-2 ( <protein>IL-2</protein> ) promoter activity stimulated by cross-linking of <protein>CD2</protein> , <protein>TCR</protein> /CD3 , and <protein>CD28</protein> with <protein>antibodies</protein> was significantly reduced by transient expression of an <protein>Itk mutant</protein> lacking the kinase activity .


The reduction paralleled a decrease in tyrosine phosphorylation of endogenous wild-type Itk .

The reduction paralleled a decrease in tyrosine phosphorylation of <protein>endogenous wild-type Itk</protein> .


Stimulation of CD2 or TCR/CD3 induced activation of the nuclear factor of activated T cells ( NFAT ) , the binding site of which is included in the IL-2 gene promoter .

Stimulation of <protein>CD2</protein> or <protein>TCR/CD3</protein> induced activation of the <protein>nuclear factor of activated T cells</protein> ( <protein>NFAT</protein> ) , the <dna>binding site</dna> of which is included in the <dna>IL-2 gene promoter</dna> .


The activation of NFAT was also impaired by expression of the Itk mutant .

The activation of <protein>NFAT</protein> was also impaired by expression of the <protein>Itk mutant</protein> .


These results demonstrate that Itk plays a role in IL-2 production , indicating a critical involvement of Itk in the initial stage of T cell activation by mediating signals from the TCR/CD3 complex , CD2 , and CD28 .

These results demonstrate that <protein>Itk</protein> plays a role in <protein>IL-2</protein> production , indicating a critical involvement of <protein>Itk</protein> in the initial stage of T cell activation by mediating signals from the <protein>TCR/CD3 complex</protein> , <protein>CD2</protein> , and <protein>CD28</protein> .


Expression of LAZ3/BCL6 in follicular center ( FC ) B cells of reactive lymph nodes and FC-derived non-Hodgkin lymphomas .

Expression of <protein>LAZ3/BCL6</protein> in follicular center ( FC ) B cells of reactive lymph nodes and FC-derived non-Hodgkin lymphomas .


Chromosomal translocation resulting in abnormal expression of the LAZ3/BCL6 gene in B cells has been implicated in the tumorigenesis of non-Hodgkin lymphoma ( NHL ) .

Chromosomal translocation resulting in abnormal expression of the <dna>LAZ3/BCL6 gene</dna> in <cell_type>B cells</cell_type> has been implicated in the tumorigenesis of non-Hodgkin lymphoma ( NHL ) .


Therefore we studied the expression pattern of LAZ3/BCL6 by in situ hybridization with synthetic oligonucleotide probes in frozen tissue sections from five reactive lymph nodes and 38 B cell and non-B NHL .

Therefore we studied the expression pattern of <protein>LAZ3/BCL6</protein> by in situ hybridization with synthetic oligonucleotide probes in frozen tissue sections from five reactive lymph nodes and 38 B cell and non-B NHL .


In addition , we investigated the expression of LAZ3/BCL6 by Northern blot analysis on multiple human tissues .

In addition , we investigated the expression of <protein>LAZ3/BCL6</protein> by Northern blot analysis on multiple human tissues .


The LAZ3/BCL6 transcript was found in a variety of tissues , including skeletal muscle , peripheral blood leukocytes , and weakly in normal lymph nodes .

The <rna>LAZ3/BCL6 transcript</rna> was found in a variety of tissues , including skeletal muscle , <cell_type>peripheral blood leukocytes</cell_type> , and weakly in normal lymph nodes .


In the tumor samples , expression of LAZ3/BCL6 was observed in 68 % of all B cell NHL and none of the non-B lymphomas .

In the tumor samples , expression of <protein>LAZ3/BCL6</protein> was observed in 68 % of all B cell NHL and none of the non-B lymphomas .


All cases of follicular , mixed small and large cell lymphomas showed LAZ3/BCL6 expression confined to the neoplastic follicles .

All cases of follicular , mixed small and large cell lymphomas showed <protein>LAZ3/BCL6</protein> expression confined to the neoplastic follicles .


A follicular expression pattern was also found in all non-malignant reactive lymph nodes .


Hence , the expression of LAZ3/BCL6 does not correlate to malignancy , but reflects the origin of B cells from the germinal centers .

Hence , the expression of <protein>LAZ3/BCL6</protein> does not correlate to malignancy , but reflects the origin of <cell_type>B cells</cell_type> from the germinal centers .


Jak1 expression is required for mediating interleukin-4-induced tyrosine phosphorylation of insulin receptor substrate and Stat6 signaling molecules .

<protein>Jak1</protein> expression is required for mediating interleukin-4-induced tyrosine phosphorylation of insulin receptor substrate and <protein>Stat6</protein> <protein>signaling molecules</protein> .


The Jak1 , Jak2 , Jak3 , and Fes tyrosine kinases have been demonstrated to undergo tyrosine phosphorylation in response to interleukin ( IL ) -4 stimulation in different cell systems .

The <protein>Jak1 , Jak2 , Jak3 , and Fes tyrosine kinases</protein> have been demonstrated to undergo tyrosine phosphorylation in response to <protein>interleukin ( IL ) -4</protein> stimulation in different cell systems .


However , it is not clear which , if any , of these kinases are responsible for initiating IL-4-induced tyrosine phosphorylation of intracellular substrates in vivo .

However , it is not clear which , if any , of these kinases are responsible for initiating IL-4-induced tyrosine phosphorylation of <protein>intracellular substrates</protein> in vivo .


In the present study , we have utilized a mutant Jak1-deficient HeLa cell line , E1C3 , and its parental Jak1-expressing counterpart , 1D4 , to analyze the role of Jak1 in mediating IL-4-induced tyrosine phosphorylation events .

In the present study , we have utilized a <cell_line>mutant Jak1-deficient HeLa cell line</cell_line> , <cell_line>E1C3</cell_line> , and its <cell_line>parental Jak1-expressing counterpart</cell_line> , <cell_line>1D4</cell_line> , to analyze the role of <protein>Jak1</protein> in mediating IL-4-induced tyrosine phosphorylation events .


IL-4 treatment rapidly induced tyrosine phosphorylation of insulin receptor substrate ( IRS ) -1 and IRS-2 in 1D4 but not in E1C3 cells .

IL-4 treatment rapidly induced tyrosine phosphorylation of <protein>insulin receptor substrate ( IRS ) -1</protein> and <protein>IRS-2</protein> in <cell_line>1D4</cell_line> but not in <cell_line>E1C3 cells</cell_line> .


IL-4 -mediated tyrosine phosphorylation of Stat6 was pronounced in 1D4 cells , while no IL-4 -induced Stat6 phosphorylation was detected in E1C3 cells .

<protein>IL-4</protein> -mediated tyrosine phosphorylation of <protein>Stat6</protein> was pronounced in <cell_line>1D4 cells</cell_line> , while no <protein>IL-4</protein> -induced <protein>Stat6</protein> phosphorylation was detected in <cell_line>E1C3 cells</cell_line> .


IL-4 also induced Stat6 DNA binding activity from lysates of 1D4 but not E1C3 cells utilizing a radiolabeled immunoglobulin heavy chain germline epsilon promotor sequence ( Iepsilon ) in an electrophoretic mobility shift assay .

<protein>IL-4</protein> also induced <protein>Stat6</protein> DNA binding activity from lysates of <cell_line>1D4</cell_line> but not <cell_line>E1C3 cells</cell_line> utilizing a <dna>radiolabeled immunoglobulin heavy chain germline epsilon promotor sequence</dna> ( <dna>Iepsilon</dna> ) in an electrophoretic mobility shift assay .


Reconstitution of Jak1 expression in E1C3 cells restored the ability of IL-4 to induce IRS and Stat6 tyrosine phosphorylation .

Reconstitution of <protein>Jak1</protein> expression in <cell_line>E1C3 cells</cell_line> restored the ability of <protein>IL-4</protein> to induce <dna>IRS</dna> and <protein>Stat6</protein> tyrosine phosphorylation .


These results provide evidence that Jak1 expression is required for mediating tyrosine phosphorylation and activation of crucial molecules involved in IL-4 signal transduction .

These results provide evidence that <protein>Jak1</protein> expression is required for mediating tyrosine phosphorylation and activation of crucial molecules involved in <protein>IL-4</protein> signal transduction .


Oxidant-regulation of gene expression in the chronically inflamed intestine .


It is becoming increasingly apparent that the chronic gut inflammation observed in the idiopathic inflammatory bowel diseases ( e.g. ulcerative colitis , Crohn 's disease ) is associated with enhanced production of leukocyte-derived oxidants .


Oxidants such as hydrogen peroxide are known to activate certain transcription factors such as nuclear transcription factor kappa beta .

Oxidants such as hydrogen peroxide are known to activate certain <protein>transcription factors</protein> such as <protein>nuclear transcription factor kappa beta</protein> .


Nuclear transcription factor kB ( NF-kappa B ) is a ubiquitous transcription factor and pleiotropic regulator of numerous genes involved in the immune and inflammatory responses .

<protein>Nuclear transcription factor kB</protein> ( <protein>NF-kappa B</protein> ) is a <protein>ubiquitous transcription factor</protein> and <protein>pleiotropic regulator</protein> of numerous genes involved in the immune and inflammatory responses .


This transcription factor is activated via the selective phosphorylation , ubiquination and degradation of its inhibitor protein I-kB thereby allowing translocation of NF-kappa B into the nucleus where it upregulates the transcription of a variety of adhesion molecules ( e.g . ICAM-1 , VCAM-1 ) , cytokines ( TNF , IL-1 , IL-6 ) and enzymes ( iNOS ) .

This <protein>transcription factor</protein> is activated via the selective phosphorylation , ubiquination and degradation of its <protein>inhibitor protein I-kB</protein> thereby allowing translocation of <protein>NF-kappa B</protein> into the nucleus where it upregulates the transcription of a variety of <protein>adhesion molecules</protein> ( e.g . <protein>ICAM-1</protein> , <protein>VCAM-1</protein> ) , <protein>cytokines</protein> ( <protein>TNF</protein> , <protein>IL-1</protein> , <protein>IL-6</protein> ) and <protein>enzymes</protein> ( <protein>iNOS</protein> ) .


The proteolytic degradation of the post-translationally modified I-kappa B is known to be mediated by the 26S proteasome complex .

The proteolytic degradation of the post-translationally modified <protein>I-kappa B</protein> is known to be mediated by the <protein>26S proteasome complex</protein> .


Based upon work from our laboratory , we propose that inhibition of NF-kappa B activation produces significant anti inflammatory activity which may be mediated by the inhibition of transcription of certain pro-inflammatory mediators and adhesion molecules .

Based upon work from our laboratory , we propose that inhibition of <protein>NF-kappa B</protein> activation produces significant anti inflammatory activity which may be mediated by the inhibition of transcription of certain <protein>pro-inflammatory mediators</protein> and <protein>adhesion molecules</protein> .


Generation of cytotoxic T lymphocytes against immunorecessive epitopes after multiple immunizations with adenovirus vectors is dependent on haplotype .

Generation of <cell_type>cytotoxic T lymphocytes</cell_type> against <protein>immunorecessive epitopes</protein> after multiple immunizations with adenovirus vectors is dependent on haplotype .


Currently , adenovirus ( Ad ) is being considered as a vector for the treatment of cystic fibrosis as well as other diseases .


However , the cytotoxic T lymphocyte ( CTL ) response to Ad could limit the effectiveness of such approaches .

However , the <cell_type>cytotoxic T lymphocyte</cell_type> ( <cell_type>CTL</cell_type> ) response to Ad could limit the effectiveness of such approaches .


Since the CTL response to virus infection is often focused on one or a few immunodominant epitopes , one approach to circumvent this response is to create vectors that lack these immunodominant epitopes .

Since the <cell_type>CTL</cell_type> response to virus infection is often focused on one or a few <protein>immunodominant epitopes</protein> , one approach to circumvent this response is to create vectors that lack these <protein>immunodominant epitopes</protein> .


The effectiveness of this approach was tested by immunizing mice with human group C adenoviruses .


Three mouse strains ( C57BL/10SnJ [ H-2b ] , C3HeB/FeJ [ H-2k ] , and BALB/cByJ [ H-2d ] ) were immunized with wild-type Ad or Ad vectors lacking the immunodominant antigen ( s ) , and the CTL responses were measured .

Three mouse strains ( C57BL/10SnJ [ H-2b ] , C3HeB/FeJ [ H-2k ] , and BALB/cByJ [ H-2d ] ) were immunized with wild-type Ad or Ad vectors lacking the <protein>immunodominant antigen</protein> ( s ) , and the <cell_type>CTL</cell_type> responses were measured .


In C57BL/10 ( B10 ) mice , a single inoculation intraperitoneally ( i.p. ) led to the recognition of an immunodominant antigen in E1A .

In C57BL/10 ( B10 ) mice , a single inoculation intraperitoneally ( i.p. ) led to the recognition of an <protein>immunodominant antigen</protein> in <dna>E1A</dna> .


When B10 mice were inoculated multiple times either i.p .


or intranasally with wild-type Ad or an Ad vector lacking most of the E1 region , subdominant epitopes outside this region were recognized .

or intranasally with wild-type Ad or an Ad vector lacking most of the <dna>E1 region</dna> , subdominant epitopes outside this region were recognized .


In contrast , C3H mice inoculated with wild-type Ad recognized an epitope mapping within E1B . When inoculated twice with Ad vectors lacking both E1A and E1B , no immunorecessive epitopes were recognized .

In contrast , C3H mice inoculated with wild-type Ad recognized an epitope mapping within <dna>E1B</dna> . When inoculated twice with Ad vectors lacking both <dna>E1A</dna> and <dna>E1B</dna> , no <protein>immunorecessive epitopes</protein> were recognized .


The immune response to Ad in BALB/c mice was more complex .


CTLs from BALB/c mice inoculated i.p. with wild-type Ad recognized E1B in the context of the major histocompatibility complex ( MHC ) class I Dd allele and a region outside E1 associated with the Kd allele .

<cell_type>CTLs</cell_type> from BALB/c mice inoculated i.p. with wild-type Ad recognized <dna>E1B</dna> in the context of the <dna>major histocompatibility complex ( MHC ) class I Dd allele</dna> and a region outside <dna>E1</dna> associated with the <dna>Kd allele</dna> .


When BALB/c mice were inoculated with E1 -deleted Ad vectors , only the immunodominant Kd-restricted epitope was recognized , and Dd-restricted CTLs did not develop .

When BALB/c mice were inoculated with <dna>E1</dna> -deleted Ad vectors , only the <protein>immunodominant Kd-restricted epitope</protein> was recognized , and Dd-restricted <cell_type>CTLs</cell_type> did not develop .


This report indicates that the emergence of CTLs against immunorecessive epitopes following multiple administrations of Ad vectors lacking immunodominant antigens is dependent on haplotype and could present an obstacle to gene therapy in an MHC -diverse human population .

This report indicates that the emergence of <cell_type>CTLs</cell_type> against <protein>immunorecessive epitopes</protein> following multiple administrations of Ad vectors lacking immunodominant antigens is dependent on haplotype and could present an obstacle to gene therapy in an <protein>MHC</protein> -diverse human population .


Characterization of the human platelet/endothelial cell adhesion molecule-1 promoter : identification of a GATA-2 binding element required for optimal transcriptional activity .

Characterization of the <dna>human platelet/endothelial cell adhesion molecule-1 promoter</dna> : identification of a <dna>GATA-2 binding element</dna> required for optimal transcriptional activity .


Platelet/endothelial cell adhesion molecule-1 ( PECAM-1 ) is a 130-kD member of the Ig gene superfamily that is expressed on platelets , endothelial cells , and certain leukocyte subsets .

<protein>Platelet/endothelial cell adhesion molecule-1</protein> ( <protein>PECAM-1</protein> ) is a <protein>130-kD member</protein> of the <dna>Ig gene superfamily</dna> that is expressed on <cell_type>platelets</cell_type> , <cell_type>endothelial cells</cell_type> , and certain <cell_type>leukocyte subsets</cell_type> .


To examine the factors controlling vascular-specific expression of PECAM-1 , we cloned the 5'-flanking region of the PECAM-1 gene and analyzed its transcriptional activity .

To examine the factors controlling vascular-specific expression of <protein>PECAM-1</protein> , we cloned the <dna>5'-flanking region</dna> of the <dna>PECAM-1 gene</dna> and analyzed its transcriptional activity .


5'-Rapid amplification of cDNA ends ( 5'-RACE ) analysis showed that transcription initiation occurred at several closely spaced nearby sites originating approximately 204 bp upstream from the translation start site .

5'-Rapid amplification of <dna>cDNA ends</dna> ( <dna>5'-RACE</dna> ) analysis showed that transcription initiation occurred at several closely spaced nearby sites originating approximately <dna>204 bp upstream</dna> from the <dna>translation start site</dna> .


Analysis of the sequence immediately upstream from the transcription initiation site ( TIS ) showed no canonical TATA or CAAT elements , however an initiator element commonly found in TATA-less promoters encompassed the TIS .

Analysis of the sequence immediately upstream from the <dna>transcription initiation site</dna> ( <dna>TIS</dna> ) showed no canonical <dna>TATA</dna> or <dna>CAAT elements</dna> , however an initiator element commonly found in <dna>TATA-less promoters</dna> encompassed the <dna>TIS</dna> .


5'-serially truncated PECAM-1 promoter segments cloned in front of a luciferase reporter drove transcription in both a lineage- and orientation-specific manner .

<dna>5'-serially truncated PECAM-1 promoter segments</dna> cloned in front of a <dna>luciferase reporter</dna> drove transcription in both a lineage- and orientation-specific manner .


Putative cis-acting control elements present within a 300-bp core promoter included two ets sites , an Sp1 site , tandem E-box domains , two GATA-associated sites ( CACCC ) , an AP-2 binding site , and a GATA element at -24 .

Putative <dna>cis-acting control elements</dna> present within a <dna>300-bp core promoter</dna> included two <dna>ets sites</dna> , an <dna>Sp1 site</dna> , tandem <dna>E-box domains</dna> , two <dna>GATA-associated sites</dna> ( CACCC ) , an <dna>AP-2 binding site</dna> , and a <dna>GATA element</dna> at <dna>-24</dna> .


Mutational analysis showed that optimal transcriptional activity required the GATA sequence at position -24 , and gel-shift assays further showed that the GATA-2 transcription factor , but not GATA-1 , bound to this region of the PECAM-1 promoter .

Mutational analysis showed that optimal transcriptional activity required the <dna>GATA sequence</dna> at position <dna>-24</dna> , and gel-shift assays further showed that the <protein>GATA-2 transcription factor</protein> , but not <protein>GATA-1</protein> , bound to this region of the <dna>PECAM-1 promoter</dna> .


Understanding the cis- and transacting factors that regulate the tissue-specific expression of PECAM-1 should increase our understanding of the mechanisms by which vascular-specific gene expression is achieved .

Understanding the <protein>cis- and transacting factors</protein> that regulate the tissue-specific expression of <protein>PECAM-1</protein> should increase our understanding of the mechanisms by which vascular-specific gene expression is achieved .


A negative regulatory region containing a glucocorticosteroid response element ( nGRE ) in the human interleukin-1beta gene .

A negative regulatory region containing a <dna>glucocorticosteroid response element</dna> ( <dna>nGRE</dna> ) in the <dna>human interleukin-1beta gene</dna> .


Interleukin-1 beta ( IL-1beta ) is one of the most important inflammatory mediators in human inflammatory and immunological diseases .

<protein>Interleukin-1 beta</protein> ( <protein>IL-1beta</protein> ) is one of the most important <protein>inflammatory mediators</protein> in human inflammatory and immunological diseases .


The regulation of human IL-1beta gene expression has been studied for several years , and a few regulatory elements have been discovered in the promoter region .

The regulation of <protein>human IL-1beta</protein> gene expression has been studied for several years , and a few <dna>regulatory elements</dna> have been discovered in the <dna>promoter region</dna> .


However , little is known about negative regulation of IL-1beta expression at the transcriptional level , which may play an important role in anti-inflammatory and immunosuppressive effects .

However , little is known about negative regulation of <protein>IL-1beta</protein> expression at the transcriptional level , which may play an important role in anti-inflammatory and immunosuppressive effects .


We have identified a negative regulatory element located in the region between -685 and -395 .

We have identified a <dna>negative regulatory element</dna> located in the region between <dna>-685 and -395</dna> .


Within this region , a 19-bp nuclear factor binding site ( -570 to -552 ) was characterized by DNase I footprinting and electromobility shift assay .

Within this region , a <dna>19-bp nuclear factor binding site</dna> ( <dna>-570 to -552</dna> ) was characterized by <protein>DNase I</protein> footprinting and electromobility shift assay .


A consensus sequence for a negative glucocorticoid response element ( nGRE ) and a transcription activator protein-2 binding site were noted within this footprint .

A <dna>consensus sequence</dna> for a <dna>negative glucocorticoid response element</dna> ( <dna>nGRE</dna> ) and a <dna>transcription activator protein-2 binding site</dna> were noted within this footprint .


Functional studies showed a 2.5-fold increase in promoter activity when this 19-bp binding site was deleted in the reporter constructs IL-1beta /CAT and IL-1beta /SV40 promoter /CAT .

Functional studies showed a 2.5-fold increase in promoter activity when this <dna>19-bp binding site</dna> was deleted in the <dna>reporter constructs</dna> <protein>IL-1beta</protein> <protein>/CAT</protein> and <protein>IL-1beta</protein> <dna>/SV40 promoter</dna> <protein>/CAT</protein> .


Dexamethasone ( 10 ( -8 ) M ) repressed chloramphenicol acetyltransferase ( CAT ) production by 75 % in the wild-type fragment but not in a deletion mutant lacking the 19-bp site .

Dexamethasone ( 10 ( -8 ) M ) repressed <protein>chloramphenicol acetyltransferase</protein> ( <protein>CAT</protein> ) production by 75 % in the <dna>wild-type fragment</dna> but not in a <dna>deletion mutant</dna> lacking the <dna>19-bp site</dna> .


A protein of about 150 kD that bound to this negative regulatory sequence was identified by UV cross-linking .

A protein of about <protein>150 kD</protein> that bound to this <dna>negative regulatory sequence</dna> was identified by UV cross-linking .


This is the first description of a negative regulatory region responsive to glucocorticoids in a cytokine gene .

This is the first description of a <dna>negative regulatory region</dna> responsive to glucocorticoids in a <dna>cytokine gene</dna> .


Interaction of transcription factors RFX1 and MIBP1 with the gamma motif of the negative regulatory element of the hepatitis B virus core promoter .

Interaction of <protein>transcription factors</protein> <protein>RFX1</protein> and <protein>MIBP1</protein> with the <dna>gamma motif</dna> of the <dna>negative regulatory element</dna> of the <dna>hepatitis B virus core promoter</dna> .


The negative regulatory element ( NRE ) of the hepatitis B virus ( HBV ) core promoter contains three subregions which act synergistically to suppress core promoter activity .

The <dna>negative regulatory element</dna> ( <dna>NRE</dna> ) of the <dna>hepatitis B virus ( HBV ) core promoter</dna> contains three subregions which act synergistically to suppress core promoter activity .


One of these subregions , NRE gamma , is active in both HeLa cervical carcinoma cells and Huh7 hepatoma cells and was found to be bound by a protein factor present in both cell types .

One of these subregions , <dna>NRE gamma</dna> , is active in both <cell_line>HeLa cervical carcinoma cells</cell_line> and <cell_line>Huh7 hepatoma cells</cell_line> and was found to be bound by a protein factor present in both cell types .


Here we show that the transcription factor RFX1 can bind to NRE gamma and transactivate the core promoter through this site .

Here we show that the <protein>transcription factor</protein> <protein>RFX1</protein> can bind to <dna>NRE gamma</dna> and transactivate the <dna>core promoter</dna> through this site .


Mutations which abrogated the gene-suppressive activity of NRE gamma prevented RFX1 from binding to NRE gamma .

Mutations which abrogated the gene-suppressive activity of <dna>NRE gamma</dna> prevented <protein>RFX1</protein> from binding to <dna>NRE gamma</dna> .


In addition , RFX1 can bind simultaneously , most likely as a heterodimer , with the transcription factor MIBP1 to NRE gamma .

In addition , <protein>RFX1</protein> can bind simultaneously , most likely as a <protein>heterodimer</protein> , with the <protein>transcription factor</protein> <protein>MIBP1</protein> to <dna>NRE gamma</dna> .


In the absence of a cloned MIBP1 gene for further studies , we hypothesize that RFX1 acts with MIBP1 to negatively regulate the core promoter activity through the NRE gamma site .

In the absence of a cloned <dna>MIBP1 gene</dna> for further studies , we hypothesize that <protein>RFX1</protein> acts with <protein>MIBP1</protein> to negatively regulate the core promoter activity through the <dna>NRE gamma site</dna> .


The ability of RFX1 to transactivate the core promoter raises the possibility that RFX1 may play a dual role in regulating HBV gene expression

The ability of <protein>RFX1</protein> to transactivate the <dna>core promoter</dna> raises the possibility that <protein>RFX1</protein> may play a dual role in regulating HBV gene expression


Use of arsenic trioxide ( As2O3 ) in the treatment of acute promyelocytic leukemia ( APL ) : II .


Clinical efficacy and pharmacokinetics in relapsed patients .


The therapeutic effect of arsenic trioxide ( As2O3 ) in the treatment of acute promyelocytic leukemia ( APL ) was evaluated among 15 APL patients at relapse after all-trans retinoic acid ( ATRA ) induced and chemotherapy maintained complete remission ( CR ) .


As2O3 was administered intravenously at the dose of 10 mg/d .


Clinical CR was achieved in nine of 10 ( 90 % ) patients treated with As2O3 alone and in the remaining five patients treated by the combination of As2O3 and low-dose chemotherapeutic drugs or ATRA .


During the treatment with As2O3 , there was no bone marrow depression and only limited side effects were encountered .


Pharmacokinetic studies , which were performed in eight patients , showed that after a peak level of 5.54 micromol/L to 7.30 micromol/L , plasma arsenic was rapidly eliminated , and the continuous administration of As2O3 did not alter its pharmacokinetic behaviors .


In addition , increased amounts of arsenic appeared in the urine , with a daily excretion accounting for approximately 1 % to 8 % of the total daily dose administered .


Arsenic contents in hair and nail were increased , and the peak content of arsenic could reach 2.5 to 2.7 microg/g tissue at CR .


On the other hand , a decline of the arsenic content in hair and nail was observed after withdrawal of the drug .


We conclude that As2O3 treatment is an effective and relatively safe drug in APL patients refractory to ATRA and conventional chemotherapy .


Nucleolin is one component of the B cell-specific transcription factor and switch region binding protein , LR1 .

<protein>Nucleolin</protein> is one component of the <protein>B cell-specific transcription factor</protein> and <protein>switch region binding protein</protein> , <protein>LR1</protein> .


LR1 is a B cell-specific , sequence-specific DNA binding activity that regulates transcription in activated B cells .

<protein>LR1</protein> is a B cell-specific , sequence-specific DNA binding activity that regulates transcription in <cell_type>activated B cells</cell_type> .


LR1 also binds Ig heavy chain switch region sequences and may function in class switch recombination .

<protein>LR1</protein> also binds <protein>Ig heavy chain</protein> switch region sequences and may function in class switch recombination .


LR1 contains two polypeptides , of 106 kDa and 45 kDa , and here we report that the 106-kDa component of LR1 is nucleolin .

<protein>LR1</protein> contains two polypeptides , of 106 kDa and 45 kDa , and here we report that the <protein>106-kDa component</protein> of <protein>LR1</protein> is <protein>nucleolin</protein> .


This identification , initially made by microsequence analysis , was verified by showing that ( i ) LR1 -DNA binding activity increased in B cells transfected with a nucleolin cDNA expression construct ; ( ii ) LR1 -DNA binding activity was recognized by antibodies raised against recombinant human nucleolin ; and ( iii ) in B cells transfected with epitope-tagged nucleolin expression constructs , the LR1-DNA complex was recognized by the anti-tag antibody .

This identification , initially made by microsequence analysis , was verified by showing that ( i ) <protein>LR1</protein> -DNA binding activity increased in <cell_type>B cells</cell_type> transfected with a <dna>nucleolin cDNA expression construct</dna> ; ( ii ) <protein>LR1</protein> -DNA binding activity was recognized by antibodies raised against <protein>recombinant human nucleolin</protein> ; and ( iii ) in <cell_type>B cells</cell_type> transfected with <dna>epitope-tagged nucleolin expression constructs</dna> , the <protein>LR1-DNA complex</protein> was recognized by the <protein>anti-tag antibody</protein> .


Nucleolin is an abundant nucleolar protein which is believed to play a role in rDNA transcription or organization , or rRNA processing .

<protein>Nucleolin</protein> is an <protein>abundant nucleolar protein</protein> which is believed to play a role in <dna>rDNA</dna> transcription or organization , or <rna>rRNA</rna> processing .


Homology between nucleolin and histone H1 suggests that nucleolin may alter DNA organization in response to cell cycle controls , and the nucleolin component of LR1 may therefore function to organize switch regions before , during , or after switch recombination .

Homology between <protein>nucleolin</protein> and <protein>histone H1</protein> suggests that <protein>nucleolin</protein> may alter DNA organization in response to cell cycle controls , and the <protein>nucleolin</protein> component of <protein>LR1</protein> may therefore function to organize <dna>switch regions</dna> before , during , or after switch recombination .


The demonstration that nucleolin is a component of a B cell-specific complex that binds switch region sequences suggests that the G-rich switch regions may have evolved from rDNA .

The demonstration that <protein>nucleolin</protein> is a component of a <protein>B cell-specific complex</protein> that binds switch region sequences suggests that the <dna>G-rich switch regions</dna> may have evolved from <dna>rDNA</dna> .


Glucocorticoid-resistance in peripheral-blood lymphocytes does not correlate with number of affinity of glucocorticoid-receptors in chronic renal failure patients .

Glucocorticoid-resistance in <cell_type>peripheral-blood lymphocytes</cell_type> does not correlate with number of affinity of <protein>glucocorticoid-receptors</protein> in chronic renal failure patients .


Glucocorticoid ( GC ) resistance in patients with chronic renal failure ( CRF ) seriously impairs successive GC therapy after renal transplantation .


We examined the relationship between GC-receptor ( GC-R ) parameters in peripheral-blood mononuclear cells ( PBMC ) and PBMC resistance to GC in 21 CRF patients and 18 healthy subjects .

We examined the relationship between GC-receptor ( GC-R ) parameters in <cell_type>peripheral-blood mononuclear cells</cell_type> ( <cell_type>PBMC</cell_type> ) and <cell_type>PBMC</cell_type> resistance to GC in 21 CRF patients and 18 healthy subjects .


Each subject group was divided into two subgroups according to PBMC sensitivity to prednisolone in a mitogen assay procedure ; i.e. , sensitive ( IC50 < 381 ng/mL ) and resistant ( IC50 > 381 ng/mL ) groups .

Each subject group was divided into two subgroups according to <cell_type>PBMC</cell_type> sensitivity to prednisolone in a mitogen assay procedure ; i.e. , sensitive ( IC50 < 381 ng/mL ) and resistant ( IC50 > 381 ng/mL ) groups .


In healthy subjects , the mean GC-R Bmax and Kd in quiescent PBMC of the GC-sensitive group were 2.89 +/- 1.23 fmol/10 ( 6 ) cells and 4.00 +/- 2.24 nM , respectively .

In healthy subjects , the mean <protein>GC-R</protein> Bmax and Kd in quiescent <cell_type>PBMC</cell_type> of the GC-sensitive group were 2.89 +/- 1.23 fmol/10 ( 6 ) cells and 4.00 +/- 2.24 nM , respectively .


The Bmax in these subjects significantly increased to 6.61 +/- 2.02 ( 257.7 +/- 107.8 % ) after 24 h stimulation with concanavalin A ( p < 0.01 ) , while the Kd change was not significant .


The GC-R Bmax and Kd in quiescent PBMC of the GC-resistant group were 5.33 +/- 1.37 fmol/10 ( 6 ) cells and 3.20 +/- 1.39 nM , respectively .

The <protein>GC-R</protein> Bmax and Kd in quiescent <cell_type>PBMC</cell_type> of the GC-resistant group were 5.33 +/- 1.37 fmol/10 ( 6 ) cells and 3.20 +/- 1.39 nM , respectively .


Both of these parameters , however , did not change significantly after mitogen stimulation .

Both of these parameters , however , did not change significantly after <protein>mitogen</protein> stimulation .


There was a significant negative correlation between IC50S of prednisolone and increase-ratios ( post/pre ratio ) of Bmax after mitogen stimulation ( p < 0.05 ) .

There was a significant negative correlation between IC50S of prednisolone and increase-ratios ( post/pre ratio ) of Bmax after <protein>mitogen</protein> stimulation ( p < 0.05 ) .


In CRF patients , Bmax and Kd in quiescent PBMC of the GC-sensitive group were 6.04 +/- 2.35 fmol/10 ( 6 ) cells and 3.49 +/- 1.72 nM , respectively , while those in PBMC of the GC-resistant group were 5.13 +/- 2.31 fmol/10 ( 6 ) cells and 4.04 +/- 1.62 nM , respectively .

In CRF patients , Bmax and Kd in quiescent <cell_type>PBMC</cell_type> of the GC-sensitive group were 6.04 +/- 2.35 fmol/10 ( 6 ) cells and 3.49 +/- 1.72 nM , respectively , while those in <cell_type>PBMC</cell_type> of the GC-resistant group were 5.13 +/- 2.31 fmol/10 ( 6 ) cells and 4.04 +/- 1.62 nM , respectively .


The Bmax and Kd were not significantly changed after mitogen stimulation in both subgroups of CRF .

The Bmax and Kd were not significantly changed after <protein>mitogen</protein> stimulation in both subgroups of CRF .


Moreover , in contrast to healthy subjects , there was no correlation between IC50 and GC-R parameters in CRF .

Moreover , in contrast to healthy subjects , there was no correlation between IC50 and <protein>GC-R</protein> parameters in CRF .


We concluded that , in healthy subjects , decreased PBMC capacity to amplify GC-R numbers in response to mitogen is correlated with GC resistance , whereas in CRF patients the resistant mechanism is not correlated with GC-R parameters .

We concluded that , in healthy subjects , decreased <cell_type>PBMC</cell_type> capacity to amplify <protein>GC-R</protein> numbers in response to <protein>mitogen</protein> is correlated with GC resistance , whereas in CRF patients the resistant mechanism is not correlated with <protein>GC-R</protein> parameters .


An unknown event might be involved in GC-resistance of CRF .


Alteration of a single serine in the basic domain of the Epstein-Barr virus ZEBRA protein separates its functions of transcriptional activation and disruption of latency .

Alteration of a single serine in the <protein>basic domain</protein> of the <protein>Epstein-Barr virus ZEBRA protein</protein> separates its functions of transcriptional activation and disruption of latency .


The ZEBRA protein from Epstein-Barr virus ( EBV ) activates a switch from the latent to the lytic expression program of the virus .

The <protein>ZEBRA protein</protein> from Epstein-Barr virus ( EBV ) activates a switch from the latent to the lytic expression program of the virus .


ZEBRA , a member of the bZIP family of DNA-binding proteins , is a transcriptional activator capable of inducing expression from viral lytic cycle promoters .

<protein>ZEBRA</protein> , a member of the <protein>bZIP family</protein> of <protein>DNA-binding proteins</protein> , is a transcriptional activator capable of inducing expression from <dna>viral lytic cycle promoters</dna> .


It had previously been thought that ZEBRA 's capacity to disrupt EBV latency resided primarily in its ability to activate transcription of genes that encode products required for lytic replication .

It had previously been thought that <protein>ZEBRA</protein> 's capacity to disrupt EBV latency resided primarily in its ability to activate transcription of genes that encode products required for lytic replication .


We generated a point mutant of ZEBRA , Z ( S186A ) , that was not impaired in its ability to activate transcription ; however , this mutation abolished its ability to initiate the viral lytic cascade .

We generated a point mutant of <protein>ZEBRA</protein> , <protein>Z ( S186A )</protein> , that was not impaired in its ability to activate transcription ; however , this mutation abolished its ability to initiate the viral lytic cascade .


The mutant , containing a serine-to-alanine substitution in the DNA-binding domain of the protein , bound to several known ZEBRA-binding sites and activated transcription from reporters bearing known ZEBRA-responsive promoters but did not disrupt latency in EBV-infected cell lines .

The mutant , containing a serine-to-alanine substitution in the <protein>DNA-binding domain</protein> of the protein , bound to several known <dna>ZEBRA-binding sites</dna> and activated transcription from reporters bearing known <dna>ZEBRA-responsive promoters</dna> but did not disrupt latency in <cell_line>EBV-infected cell lines</cell_line> .


Therefore , initiation of the EBV lytic cycle by the ZEBRA protein requires a function in addition to transcriptional activation ; a change of serine 186 to alanine in the DNA-binding domain of ZEBRA abolished this additional function and uncovered a new role for the ZEBRA protein in disruption of EBV latency .

Therefore , initiation of the EBV lytic cycle by the <protein>ZEBRA protein</protein> requires a function in addition to transcriptional activation ; a change of serine 186 to alanine in the <protein>DNA-binding domain</protein> of <protein>ZEBRA</protein> abolished this additional function and uncovered a new role for the <protein>ZEBRA protein</protein> in disruption of EBV latency .


The additional function that is required for initiation of the lytic viral life cycle is likely to require phosphorylation of serine 186 of the ZEBRA protein , which may influence either DNA recognition or transcriptional activation of lytic viral promoters in a chromatinized viral episome .

The additional function that is required for initiation of the lytic viral life cycle is likely to require phosphorylation of serine 186 of the <protein>ZEBRA protein</protein> , which may influence either DNA recognition or transcriptional activation of <dna>lytic viral promoters</dna> in a <dna>chromatinized viral episome</dna> .


Immune hyperactivation of HIV-1-infected T cells mediated by Tat and the CD28 pathway .

Immune hyperactivation of <cell_type>HIV-1-infected T cells</cell_type> mediated by <protein>Tat</protein> and the <protein>CD28</protein> pathway .


Human immunodeficiency virus-type 1 ( HIV-1 ) infection is characterized by a chronic state of immune hyperactivation in patients .


Infection of human peripheral blood lymphocytes with HIV-1 in vitro resulted in increased interleukin-2 ( IL-2 ) secretion in response to T cell activation via the CD3 and CD28 receptors .

Infection of <cell_type>human peripheral blood lymphocytes</cell_type> with HIV-1 in vitro resulted in increased interleukin-2 ( IL-2 ) secretion in response to T cell activation via the <protein>CD3 and CD28 receptors</protein> .


Expression of the HIV-1 transactivator Tat recapitulated this phenotype and was associated with increased IL-2 secretion in response to costimulation with CD3 plus CD28 .

Expression of the <protein>HIV-1 transactivator</protein> <protein>Tat</protein> recapitulated this phenotype and was associated with increased <protein>IL-2</protein> secretion in response to costimulation with <protein>CD3</protein> plus <protein>CD28</protein> .


IL-2 superinduction by Tat occurred at the transcriptional level , was mediated by the CD28-responsive element in the IL-2 promoter , and was exclusively dependent on the 29 amino acids encoded by the second exon of Tat .

<protein>IL-2</protein> superinduction by <protein>Tat</protein> occurred at the transcriptional level , was mediated by the <dna>CD28-responsive element</dna> in the <dna>IL-2 promoter</dna> , and was exclusively dependent on the <protein>29 amino acids</protein> encoded by the <dna>second exon of Tat</dna> .