Eed binds to K protein through a domain in its N terminus , but interestingly , this domain is not found in the Drosophila Esc .

<protein>Eed</protein> binds to <protein>K protein</protein> through a domain in its <protein>N terminus</protein> , but interestingly , this domain is not found in the Drosophila <protein>Esc</protein> .


Gal4-Eed fusion protein represses transcription of a reporter gene driven by a promoter that contains Gal4-binding DNA elements .

<protein>Gal4-Eed fusion protein</protein> represses transcription of a reporter gene driven by a promoter that contains <dna>Gal4-binding DNA elements</dna> .


Eed also represses transcription when recruited to a target promoter by Gal4-K protein .

<protein>Eed</protein> also represses transcription when recruited to a target promoter by <protein>Gal4-K protein</protein> .


Point mutations within the eed gene that are responsible for severe embryonic development abnormalities abolished the transcriptional repressor activity of Eed .

Point mutations within the eed gene that are responsible for severe embryonic development abnormalities abolished the <protein>transcriptional repressor</protein> activity of <protein>Eed</protein> .


Results of this study suggest that Eed -restricted homeotic gene expression during embryogenesis reflects the action of Eed as a transcriptional repressor .

Results of this study suggest that <protein>Eed</protein> -restricted homeotic gene expression during embryogenesis reflects the action of <protein>Eed</protein> as a <protein>transcriptional repressor</protein> .


The Eed -mediated transcriptional effects are likely to reflect the interaction of Eed with multiple molecular partners , including K protein .

The <protein>Eed</protein> -mediated transcriptional effects are likely to reflect the interaction of <protein>Eed</protein> with multiple molecular partners , including <protein>K protein</protein> .


Interferons up-regulate STAT1 , STAT2 , and IRF family transcription factor gene expression in human peripheral blood mononuclear cells and macrophages .

<protein>Interferons</protein> up-regulate <protein>STAT1</protein> , <protein>STAT2</protein> , and <protein>IRF</protein> family transcription factor gene expression in <cell_type>human peripheral blood mononuclear cells</cell_type> and <cell_type>macrophages</cell_type> .


IFN signaling is mediated by binding of IFNs to their receptors and subsequent activation of Janus tyrosine kinase ( JAK ) - STAT signaling pathway .

<protein>IFN</protein> signaling is mediated by binding of <protein>IFNs</protein> to their receptors and subsequent activation of Janus tyrosine kinase ( <protein>JAK</protein> ) - <protein>STAT</protein> signaling pathway .


Stimulation of cells with IFN-alpha leads to the assembly of IFN-stimulated gene factor 3 transcription factor complex formed by STAT1 , STAT2 , and p48 protein .

Stimulation of cells with <protein>IFN-alpha</protein> leads to the assembly of <protein>IFN-stimulated gene factor 3 transcription factor complex</protein> formed by <protein>STAT1</protein> , <protein>STAT2</protein> , and <protein>p48 protein</protein> .


IFN-gamma signaling is mediated by homodimeric STAT1 protein .

<protein>IFN-gamma</protein> signaling is mediated by <protein>homodimeric STAT1 protein</protein> .


Although these signaling molecules are expressed constitutively , there is also evidence of transcriptional regulation by IFNs .

Although these signaling molecules are expressed constitutively , there is also evidence of transcriptional regulation by <protein>IFNs</protein> .


We have characterized the expression of STAT and IFN regulatory factor ( IRF ) family transcription factors in primary human blood mononuclear cells and macrophages in response to IFN-alpha and IFN-gamma stimulation .

We have characterized the expression of <protein>STAT and IFN regulatory factor ( IRF ) family transcription factors</protein> in <cell_type>primary human blood mononuclear cells</cell_type> and <cell_type>macrophages</cell_type> in response to IFN-alpha and IFN-gamma stimulation .


We show that IFN-alpha and IFN-gamma rapidly and efficiently enhanced STAT1 , STAT2 , p48 , and IRF-1 gene expression .

We show that <protein>IFN-alpha</protein> and <protein>IFN-gamma</protein> rapidly and efficiently enhanced <protein>STAT1</protein> , <protein>STAT2</protein> , <protein>p48</protein> , and <dna>IRF-1 gene</dna> expression .


IFN-gamma induced IRF-1 gene expression more strongly than IFN-alpha .

<protein>IFN-gamma</protein> induced <dna>IRF-1 gene</dna> expression more strongly than <protein>IFN-alpha</protein> .


Stimulation experiments in the presence of protein synthesis inhibitor , cycloheximide , suggested that these genes were activated directly by IFNs .

Stimulation experiments in the presence of protein synthesis inhibitor , cycloheximide , suggested that these genes were activated directly by <protein>IFNs</protein> .


IRF-2 gene was apparently only weakly responsive to IFNs in these cells .

<dna>IRF-2 gene</dna> was apparently only weakly responsive to <protein>IFNs</protein> in these cells .


When macrophages were pretreated with low doses of IFN-gamma and then stimulated with IFN-alpha , clearly enhanced formation of specific transcription factor complexes was detected .

When <cell_type>macrophages</cell_type> were pretreated with low doses of <protein>IFN-gamma</protein> and then stimulated with <protein>IFN-alpha</protein> , clearly enhanced formation of specific <protein>transcription factor</protein> complexes was detected .


This suggests that higher intracellular levels of STAT1 , STAT2 , and p48 protein may result in enhanced signal transduction for cytokines utilizing these transcription factors .

This suggests that higher intracellular levels of <protein>STAT1</protein> , <protein>STAT2</protein> , and <protein>p48 protein</protein> may result in enhanced signal transduction for <protein>cytokines</protein> utilizing these <protein>transcription factors</protein> .


The role of nuclear factor-kappa B in cytokine gene regulation .

The role of <protein>nuclear factor-kappa B</protein> in <dna>cytokine gene</dna> regulation .


Transcription factors are DNA-binding proteins that regulate gene expression .

<protein>Transcription factors</protein> are <protein>DNA-binding proteins</protein> that regulate gene expression .


Nuclear factor-kappa B ( NF-kappa B ) is a critical transcription factor for maximal expression of many cytokines that are involved in the pathogenesis of inflammatory diseases , such as adult respiratory distress syndrome ( ARDS ) and sepsis syndrome .

<protein>Nuclear factor-kappa B</protein> ( <protein>NF-kappa B</protein> ) is a critical <protein>transcription factor</protein> for maximal expression of many <protein>cytokines</protein> that are involved in the pathogenesis of inflammatory diseases , such as adult respiratory distress syndrome ( ARDS ) and sepsis syndrome .


Activation and regulation of NF-kappa B are tightly controlled by a group of inhibitory proteins ( I kappa B ) that sequester NF-kappa B in the cytoplasm of immune/inflammatory effector cells .

Activation and regulation of <protein>NF-kappa B</protein> are tightly controlled by a group of <protein>inhibitory proteins</protein> ( <protein>I kappa B</protein> ) that sequester <protein>NF-kappa B</protein> in the cytoplasm of <cell_type>immune/inflammatory effector cells</cell_type> .


NF-kappa B activation involves signaled phosphorylation , ubiquitination , and proteolysis of I kappa B .

<protein>NF-kappa B</protein> activation involves signaled phosphorylation , ubiquitination , and proteolysis of <protein>I kappa B</protein> .


Liberated NF-kappa B migrates to the nucleus , where it binds to specific promoter sites and activates gene transcription .

Liberated <protein>NF-kappa B</protein> migrates to the nucleus , where it binds to <dna>specific promoter sites</dna> and activates gene transcription .


The activation of NF-kappa B initiates both extracellular and intracellular regulatory events that result in autoregulation of the inflammatory cascade through modulation of NF-kappa B activation .

The activation of <protein>NF-kappa B</protein> initiates both extracellular and intracellular regulatory events that result in autoregulation of the inflammatory cascade through modulation of <protein>NF-kappa B</protein> activation .


Recently , activation of NF-kappa B has been linked to ARDS and has been shown to be a critical proximal step in the initiation of neutrophilic inflammation in animal models .

Recently , activation of <protein>NF-kappa B</protein> has been linked to ARDS and has been shown to be a critical proximal step in the initiation of neutrophilic inflammation in animal models .


Activation of NF-kappa B can be inhibited in vivo by treatment with antioxidants , corticosteroids , and the induction of endotoxin tolerance .

Activation of <protein>NF-kappa B</protein> can be inhibited in vivo by treatment with antioxidants , corticosteroids , and the induction of <protein>endotoxin</protein> tolerance .


Identification of more specific and efficacious inhibitors of NF-kappa B activation might prove beneficial for the treatment of cytokine-mediated inflammatory diseases .

Identification of more specific and efficacious inhibitors of <protein>NF-kappa B</protein> activation might prove beneficial for the treatment of cytokine-mediated inflammatory diseases .


Chimeric oncoprotein E2a-Pbx1 induces apoptosis of hematopoietic cells by a p53 -independent mechanism that is suppressed by Bcl-2 .

<protein>Chimeric oncoprotein</protein> <protein>E2a-Pbx1</protein> induces apoptosis of <cell_type>hematopoietic cells</cell_type> by a <protein>p53</protein> -independent mechanism that is suppressed by <protein>Bcl-2</protein> .


The chimeric oncoprotein E2a-Pbx1 results from fusion of the E2A and PBX1 genes following t ( 1 ; 19 ) chromosomal translocations in B cell precursor acute leukemias .

The <protein>chimeric oncoprotein</protein> <protein>E2a-Pbx1</protein> results from fusion of the <dna>E2A and PBX1 genes</dna> following <dna>t ( 1 ; 19 ) chromosomal translocations</dna> in B cell precursor acute leukemias .


Experimentally B cell progenitors do not tolerate constitutive expression of E2a-Pbx1 which contrasts with transformation of several other cell types following its stable expression both in vitro and in vivo .

Experimentally <cell_type>B cell progenitors</cell_type> do not tolerate constitutive expression of <protein>E2a-Pbx1</protein> which contrasts with transformation of several other cell types following its stable expression both in vitro and in vivo .


To further investigate the effects of E2a-Pbx1 on the B cell progenitors , we conditionally expressed E2a-Pbx1 under control of a metal response element in hematopoietic precursor cell lines in vitro .

To further investigate the effects of <protein>E2a-Pbx1</protein> on the <cell_type>B cell progenitors</cell_type> , we conditionally expressed <protein>E2a-Pbx1</protein> under control of a metal response element in <cell_line>hematopoietic precursor cell lines</cell_line> in vitro .


Inducible expression of E2a-Pbx1 resulted in cell death with the morphologic and molecular features of apoptosis .

Inducible expression of <protein>E2a-Pbx1</protein> resulted in cell death with the morphologic and molecular features of apoptosis .


A structure-function analysis demonstrated that induction of apoptosis was not a dominant-negative effect of the E2a moiety but , rather , required the DNA-binding homeodomain of Pbx1 .

A structure-function analysis demonstrated that induction of apoptosis was not a dominant-negative effect of the <protein>E2a moiety</protein> but , rather , required the <protein>DNA-binding homeodomain</protein> of <protein>Pbx1</protein> .


E2a- Pbx1 -induced apoptosis proceeded through a BCL2 -responsive checkpoint eventuating in PARP inactivation but did require p53 .

E2a- <protein>Pbx1</protein> -induced apoptosis proceeded through a <protein>BCL2</protein> -responsive checkpoint eventuating in <protein>PARP</protein> inactivation but did require <protein>p53</protein> .


Constitutive expression of E2a-Pbx1 did not induce apoptosis or continued cycling of Rat-1 fibroblasts in low serum conditions .

Constitutive expression of <protein>E2a-Pbx1</protein> did not induce apoptosis or continued cycling of <cell_line>Rat-1 fibroblasts</cell_line> in low serum conditions .


These studies demonstrate that E2a-Pbx1 initiates programmed cell death of hematopoietic precursers by a mechanism that requires its chimeric transcriptional properties , but , unlike other nuclear oncoproteins , is independent of p53 .

These studies demonstrate that <protein>E2a-Pbx1</protein> initiates programmed cell death of <cell_type>hematopoietic precursers</cell_type> by a mechanism that requires its chimeric transcriptional properties , but , unlike other <protein>nuclear oncoproteins</protein> , is independent of <protein>p53</protein> .


CCAAT/enhancer binding protein epsilon is preferentially up-regulated during granulocytic differentiation and its functional versatility is determined by alternative use of promoters and differential splicing .

<protein>CCAAT/enhancer binding protein epsilon</protein> is preferentially up-regulated during granulocytic differentiation and its functional versatility is determined by alternative use of <dna>promoters</dna> and differential splicing .


CCAAT/enhancer binding protein ( C/EBP ) epsilon is a recently cloned member of the C/EBP family of transcription factors and is expressed exclusively in cells of hematopoietic origin .

<protein>CCAAT/enhancer binding protein ( C/EBP ) epsilon</protein> is a recently cloned member of the <protein>C/EBP family</protein> of <protein>transcription factors</protein> and is expressed exclusively in cells of hematopoietic origin .


The human C/EBPepsilon gene is transcribed by two alternative promoters , Palpha and Pbeta .

The <dna>human C/EBPepsilon gene</dna> is transcribed by two alternative <dna>promoters</dna> , <dna>Palpha</dna> and <dna>Pbeta</dna> .


A combination of differential splicing and alternative use of promoters generates four mRNA isoforms , of 2.6 kb and 1.3-1.5 kb in size .

A combination of differential splicing and alternative use of <dna>promoters</dna> generates four <rna>mRNA isoforms</rna> , of 2.6 kb and 1.3-1.5 kb in size .


These transcripts can encode three proteins of calculated molecular mass 32.2 kDa , 27.8 kDa , and 14.3 kDa .

These transcripts can encode three proteins of calculated molecular mass <rna>32.2 kDa</rna> , <rna>27.8 kDa</rna> , and <rna>14.3 kDa</rna> .


Accordingly , Western blots with antibodies specific for the DNA-binding domain , that is common to all forms , identify multiple proteins .

Accordingly , Western blots with <protein>antibodies</protein> specific for the DNA-binding domain , that is common to all forms , identify multiple proteins .


C/EBPepsilon mRNA was greatly induced during in vitro granulocytic differentiation of human primary CD34 ( + ) cells .

<rna>C/EBPepsilon mRNA</rna> was greatly induced during in vitro granulocytic differentiation of <cell_type>human primary CD34 ( + ) cells</cell_type> .


Retinoic acid treatment of HL60 promyelocytic leukemia cells for 24 hr induced C/EBPepsilon mRNA levels by 4-fold , while prolonged treatment gradually reduced mRNA expression to pretreatment levels .

Retinoic acid treatment of <cell_line>HL60 promyelocytic leukemia cells</cell_line> for 24 hr induced <rna>C/EBPepsilon mRNA</rna> levels by 4-fold , while prolonged treatment gradually reduced mRNA expression to pretreatment levels .


Transient transfection experiments with expression vectors for two of the isoforms demonstrated that the 32.2-kDa protein is an activator of transcription of granulocyte colony-stimulating factor receptor promoter , while the 14.3-kDa protein is not .

Transient transfection experiments with expression vectors for two of the isoforms demonstrated that the <protein>32.2-kDa protein</protein> is an activator of transcription of <dna>granulocyte colony-stimulating factor receptor promoter</dna> , while the <protein>14.3-kDa protein</protein> is not .


Thus , C/EBPepsilon is regulated in a complex fashion and may play a role in the regulation of genes involved in myeloid differentiation .

Thus , <protein>C/EBPepsilon</protein> is regulated in a complex fashion and may play a role in the regulation of genes involved in myeloid differentiation .


Effects of TPA , bryostatin 1 , and retinoic acid on PO-B , AP-1 , and AP-2 DNA binding during HL-60 differentiation .

Effects of <protein>TPA</protein> , <protein>bryostatin 1</protein> , and retinoic acid on <protein>PO-B</protein> , <protein>AP-1</protein> , and <protein>AP-2</protein> DNA binding during HL-60 differentiation .


PO-B was originally characterized as a transcriptional regulatory factor of the pro-opiomelanocortin ( POMC ) gene ; however , it has become increasingly clear that this protein may be active in tissues outside the pituitary , since it is present in diverse cell types , including differentiated HL-60 promyelocytic leukemia cells .

<protein>PO-B</protein> was originally characterized as a <protein>transcriptional regulatory factor</protein> of the <dna>pro-opiomelanocortin ( POMC ) gene</dna> ; however , it has become increasingly clear that this protein may be active in tissues outside the pituitary , since it is present in diverse cell types , including differentiated <cell_type>HL-60 promyelocytic leukemia cells</cell_type> .


We previously showed that PO-B DNA-binding is progressively induced during differentiation of promyelomonocytic leukemic HL-60 cells to the macrophage-like lineage ( with phorbol esters ) .

We previously showed that <protein>PO-B</protein> DNA-binding is progressively induced during differentiation of <cell_line>promyelomonocytic leukemic HL-60 cells</cell_line> to the <cell_type>macrophage-like lineage</cell_type> ( with phorbol esters ) .


We now report that PO-B DNA-binding in HL-60 cells is similarly induced during differentiation to the granulocytic lineage ( with either retinoic acid or dimethylsulfoxide ) .

We now report that <protein>PO-B</protein> DNA-binding in <cell_line>HL-60 cells</cell_line> is similarly induced during differentiation to the <cell_type>granulocytic lineage</cell_type> ( with either retinoic acid or dimethylsulfoxide ) .


Either a genetic or pharmacologic blockade of HL-60 differentiation prohibited these inductive effects .


These studies have prompted our interest in the dynamics of other transcription factor changes during HL-60 differentiation .

These studies have prompted our interest in the dynamics of other <protein>transcription factor</protein> changes during HL-60 differentiation .


Of these , we observed that another transcription factor ( AP-1 ) is also robustly induced at the DNA-binding level during macrophage-like HL-60 differentiation , but not during granulocytic differentiation .

Of these , we observed that another <protein>transcription factor</protein> ( <protein>AP-1</protein> ) is also robustly induced at the DNA-binding level during macrophage-like HL-60 differentiation , but not during granulocytic differentiation .


Conversely , the DNA-binding of the transcription factor AP-2 was slightly reduced by TPA -induced HL-60 differentiation but unchanged during granulocyte differentiation .

Conversely , the DNA-binding of the <protein>transcription factor</protein> <protein>AP-2</protein> was slightly reduced by <protein>TPA</protein> -induced HL-60 differentiation but unchanged during granulocyte differentiation .


From these data , we conclude that the induction of PO-B DNA binding is a general marker of HL-60 myelomonocytic differentiation , but that qualitative aspects of the induction of additional distinct transcription factors , such as AP-1 , may contribute to lineage-specific determinants of cell fate .

From these data , we conclude that the induction of <protein>PO-B</protein> DNA binding is a general marker of HL-60 myelomonocytic differentiation , but that qualitative aspects of the induction of additional distinct <protein>transcription factors</protein> , such as <protein>AP-1</protein> , may contribute to lineage-specific determinants of cell fate .


A novel genetic system to isolate a dominant negative effector on DNA-binding activity of Oct-2 .

A novel genetic system to isolate a <protein>dominant negative effector</protein> on DNA-binding activity of <protein>Oct-2</protein> .


Recent studies have revealed that interactions between transcription factors play an important role in regulation of gene expression in eukaryotic cells .

Recent studies have revealed that interactions between <protein>transcription factors</protein> play an important role in regulation of gene expression in <cell_type>eukaryotic cells</cell_type> .


To isolate cDNA clones that dominantly inhibit the DNA-binding activity of Oct-2 , chosen as a representative factor , we have developed a novel screening system .

To isolate cDNA clones that dominantly inhibit the DNA-binding activity of <protein>Oct-2</protein> , chosen as a representative factor , we have developed a novel screening system .


This employs an Escherichia coli tester strain carrying a modified lac operon as a reporter gene , with the lac operator sequence replaced by an octamer sequence .

This employs an Escherichia coli tester strain carrying a <dna>modified lac operon</dna> as a <dna>reporter gene</dna> , with the lac operator sequence replaced by an <dna>octamer sequence</dna> .


Oct-2 expressed in this tester strain represses the expression of the reporter gene and changes the phenotype of the cell from Lac+to Lac- .

<protein>Oct-2</protein> expressed in this tester strain represses the expression of the reporter gene and changes the phenotype of the cell from Lac+to Lac- .


Introduction of a cDNA expression library prepared from a human T-cell line into the Oct-2 -harboring tester strain allowed selection of three Lac+clones out of 1 x 10 ( 5 ) transformants .

Introduction of a cDNA expression library prepared from a <cell_line>human T-cell line</cell_line> into the <protein>Oct-2</protein> -harboring tester strain allowed selection of three Lac+clones out of 1 x 10 ( 5 ) transformants .


One of them , hT86 , encoding a putative zinc finger protein was found to derepress beta-galactosidase activity in the Oct-2 -harboring tester strain at the transcriptional level .

One of them , hT86 , encoding a <protein>putative zinc finger protein</protein> was found to derepress <protein>beta-galactosidase</protein> activity in the <protein>Oct-2</protein> -harboring tester strain at the transcriptional level .


In gel mobility shift assays , hT86 attenuated the intensity of the retarded band composed of the octamer probe and Oct-2 , suggesting a dominant negative effect on the DNA-binding activity of Oct-2 .

In gel mobility shift assays , hT86 attenuated the intensity of the retarded band composed of the <dna>octamer probe</dna> and <protein>Oct-2</protein> , suggesting a dominant negative effect on the DNA-binding activity of <protein>Oct-2</protein> .


The strategy described here provides a new approach for studying protein-protein interactions that govern the complex regulation of gene expression .


Tap : a novel cellular protein that interacts with tip of herpesvirus saimiri and induces lymphocyte aggregation .

<protein>Tap</protein> : a novel <protein>cellular protein</protein> that interacts with tip of herpesvirus saimiri and induces <cell_type>lymphocyte</cell_type> aggregation .


Tip of herpesvirus saimiri associates with Lck and down-regulates Lck -mediated activation .

Tip of herpesvirus saimiri associates with <protein>Lck</protein> and down-regulates <protein>Lck</protein> -mediated activation .


We identified a novel cellular Tip-associated protein ( Tap ) by a yeast two-hybrid screen .

We identified a novel cellular <protein>Tip-associated protein</protein> ( <protein>Tap</protein> ) by a yeast two-hybrid screen .


Tap associated with Tip following transient expression in COS-1 cells and stable expression in human Jurkat-T cells .

<protein>Tap</protein> associated with <protein>Tip</protein> following transient expression in <cell_line>COS-1 cells</cell_line> and stable expression in <cell_line>human Jurkat-T cells</cell_line> .


Expression of Tip and Tap in Jurkat-T cells induced dramatic cell aggregation .

Expression of <protein>Tip</protein> and <protein>Tap</protein> in <cell_line>Jurkat-T cells</cell_line> induced dramatic cell aggregation .


Aggregation was likely caused by the up-regulated surface expression of adhesion molecules including integrin alpha , L-selectin , ICAM-3 , and H-CAM .

Aggregation was likely caused by the up-regulated surface expression of <protein>adhesion molecules</protein> including <protein>integrin alpha</protein> , <protein>L-selectin</protein> , <protein>ICAM-3</protein> , and <protein>H-CAM</protein> .


Furthermore , NF-kappaB transcriptional factor of aggregated cells had approximately 40-fold higher activity than that of parental cells .

Furthermore , <protein>NF-kappaB transcriptional factor</protein> of aggregated cells had approximately 40-fold higher activity than that of <cell_type>parental cells</cell_type> .


Thus , Tap is likely to be an important cellular mediator of Tip function in T cell transformation by herpesvirus saimiri .

Thus , <protein>Tap</protein> is likely to be an important cellular mediator of <protein>Tip</protein> function in T cell transformation by herpesvirus saimiri .


Human monocyte binding to fibronectin enhances IFN-gamma -induced early signaling events .

<cell_type>Human monocyte</cell_type> binding to <protein>fibronectin</protein> enhances <protein>IFN-gamma</protein> -induced early signaling events .


Leukocyte integrins are fundamentally important in modulating adhesion to extracellular matrix components and to other cells .

<protein>Leukocyte integrins</protein> are fundamentally important in modulating adhesion to extracellular matrix components and to other cells .


This integrin-mediated adhesion controls leukocyte arrest and extravasation during the onset of inflammatory responses .


Moreover , integrin -ligand interactions trigger signaling pathways that may influence leukocyte phenotype and function at sites of inflammation .

Moreover , <protein>integrin</protein> -ligand interactions trigger signaling pathways that may influence leukocyte phenotype and function at sites of inflammation .


In the current studies , we evaluated the combinatorial effects of monocyte adhesion and IFN-gamma on intracellular signaling pathways .

In the current studies , we evaluated the combinatorial effects of monocyte adhesion and <protein>IFN-gamma</protein> on intracellular signaling pathways .


IFN-gamma triggers a well-defined signal transduction pathway , which although not directly stimulated by monocyte adherence to fibronectin or arginine-glycine-aspartate ( RGD ) -coated substrata , was enhanced significantly in these matrix-adherent cells .

<protein>IFN-gamma</protein> triggers a well-defined signal transduction pathway , which although not directly stimulated by monocyte adherence to <protein>fibronectin</protein> or <protein>arginine-glycine-aspartate ( RGD ) -coated substrata</protein> , was enhanced significantly in these <cell_type>matrix-adherent cells</cell_type> .


Compared with monocytes in suspension or adherent on plastic surfaces , monocytes adherent to fibronectin or RGD exhibited a greater than threefold increase in steady state levels of IFN-gamma-induced mRNA for the high affinity Fc gammaRI receptor .

Compared with monocytes in suspension or adherent on plastic surfaces , monocytes adherent to <protein>fibronectin</protein> or RGD exhibited a greater than threefold increase in steady state levels of <rna>IFN-gamma-induced mRNA</rna> for the <protein>high affinity Fc gammaRI receptor</protein> .


By electrophoretic mobility shift assays , this increase in mRNA was associated with a 5- to 10-fold increase in the STAT1-containing DNA-binding complex that binds to Fc gammaRI promoter elements .

By electrophoretic mobility shift assays , this increase in <rna>mRNA</rna> was associated with a 5- to 10-fold increase in the <protein>STAT1-containing DNA-binding complex</protein> that binds to <dna>Fc gammaRI promoter elements</dna> .


Furthermore , the tyrosine phosphorylation of STAT1 and the tyrosine kinases JAK1 and JAK2 was enhanced significantly in RGD-adherent monocytes compared with control cells .

Furthermore , the tyrosine phosphorylation of <protein>STAT1</protein> and the <protein>tyrosine kinases</protein> <protein>JAK1</protein> and <protein>JAK2</protein> was enhanced significantly in <cell_type>RGD-adherent monocytes</cell_type> compared with <cell_type>control cells</cell_type> .


These results suggest a novel mechanism by which integrin -mediated cell adhesion can modulate the magnitude of cytokine -induced signal transduction pathways , thereby amplifying cellular events leading to monocyte activation and inflammation .

These results suggest a novel mechanism by which <protein>integrin</protein> -mediated cell adhesion can modulate the magnitude of <protein>cytokine</protein> -induced signal transduction pathways , thereby amplifying cellular events leading to monocyte activation and inflammation .


Surfactant protein A activates NF-kappa B in the THP-1 monocytic cell line .

<protein>Surfactant protein A</protein> activates <protein>NF-kappa B</protein> in the <cell_line>THP-1 monocytic cell line</cell_line> .


The expression of many genes for which products are involved in inflammation is controlled by the transcriptional regulator nuclear factor ( NF ) -kappa B .

The expression of many genes for which products are involved in inflammation is controlled by the <protein>transcriptional regulator nuclear factor ( NF ) -kappa B</protein> .


Because surfactant protein ( SP ) A is involved in local host defense in the lung and alters immune cell function by modulating the expression of proinflammatory cytokines as well as surface proteins involved in inflammation , we hypothesized that SP-A exerts its action , at least in part , via activation of NF-kappa B .

Because <protein>surfactant protein ( SP ) A</protein> is involved in local host defense in the lung and alters immune cell function by modulating the expression of <protein>proinflammatory cytokines</protein> as well as <protein>surface proteins</protein> involved in inflammation , we hypothesized that <protein>SP-A</protein> exerts its action , at least in part , via activation of <protein>NF-kappa B</protein> .


We used gel shift assays to determine whether SP-A activated NF-kappa B in the THP-1 cell line , a human monocytic cell line .

We used gel shift assays to determine whether <protein>SP-A</protein> activated <protein>NF-kappa B</protein> in the <cell_line>THP-1 cell line</cell_line> , a <cell_line>human monocytic cell line</cell_line> .


Activation of NF-kappa B in THP-1 cells by SP-A doses as low as 1 microgram/ml occurred within 30 min of SP-A treatment , peaked at 60 min , and then declined .

Activation of <protein>NF-kappa B</protein> in <cell_line>THP-1 cells</cell_line> by <protein>SP-A</protein> doses as low as 1 microgram/ml occurred within 30 min of <protein>SP-A</protein> treatment , peaked at 60 min , and then declined .


This activation is inhibited by known inhibitors of NF-kappa B or by simultaneous treatment of the cells with surfactant lipids .

This activation is inhibited by known inhibitors of <protein>NF-kappa B</protein> or by simultaneous treatment of the cells with surfactant lipids .


Moreover , the NF-kappa B inhibitors blocked SP-A -dependent increases in tumor necrosis factor-alpha mRNA levels .

Moreover , the <protein>NF-kappa B inhibitors</protein> blocked <protein>SP-A</protein> -dependent increases in <rna>tumor necrosis factor-alpha mRNA</rna> levels .


These observations suggest a mechanism by which SP-A plays a role in the pathogenesis of some lung conditions and point to potential therapeutic measures that could be used to prevent SP-A induced inflammation in the lung .

These observations suggest a mechanism by which <protein>SP-A</protein> plays a role in the pathogenesis of some lung conditions and point to potential therapeutic measures that could be used to prevent <protein>SP-A</protein> induced inflammation in the lung .


GABP factors bind to a distal interleukin 2 ( IL-2 ) enhancer and contribute to c-Raf -mediated increase in IL-2 induction .

<protein>GABP factors</protein> bind to a <dna>distal interleukin 2 ( IL-2 ) enhancer</dna> and contribute to <protein>c-Raf</protein> -mediated increase in <protein>IL-2</protein> induction .


Triggering of the T-cell receptor-CD3 complex activates two major signal cascades in T lymphocytes , ( i ) Ca2+-dependent signal cascades and ( ii ) protein kinase cascades .

Triggering of the <protein>T-cell receptor-CD3 complex</protein> activates two major signal cascades in <cell_type>T lymphocytes</cell_type> , ( i ) Ca2+-dependent signal cascades and ( ii ) <protein>protein kinase</protein> cascades .


Both signal cascades contribute to the induction of the interleukin 2 ( IL-2 ) gene during T-cell activation .

Both signal cascades contribute to the induction of the <dna>interleukin 2 ( IL-2 ) gene</dna> during T-cell activation .


Prominent protein kinase cascades are those that activate mitogen-activated protein ( MAP ) kinases .

Prominent <protein>protein kinase</protein> cascades are those that activate <protein>mitogen-activated protein ( MAP ) kinases</protein> .


We show here that c-Raf , which is at the helm of the classic MAP- Erk cascade , contributes to IL-2 induction through a distal enhancer element spanning the nucleotides from positions -502 to -413 in front of the transcriptional start site of the IL-2 gene .

We show here that <protein>c-Raf</protein> , which is at the helm of the classic MAP- <protein>Erk</protein> cascade , contributes to <protein>IL-2</protein> induction through a <dna>distal enhancer element</dna> spanning the nucleotides from positions -502 to -413 in front of the transcriptional start site of the <dna>IL-2 gene</dna> .


Induction of this distal IL-2 enhancer differs from induction of the proximal IL-2 promoter-enhancer , since it is induced by phorbol esters alone and independent from Ca2+ signals .

Induction of this <dna>distal IL-2 enhancer</dna> differs from induction of the <dna>proximal IL-2 promoter-enhancer</dna> , since it is induced by phorbol esters alone and independent from Ca2+ signals .


In DNA-protein binding studies , we detected the binding of transcription factors GABP alpha and -beta to a dyad symmetry element ( DSE ) of the distal enhancer , which is formed by palindromic binding sites of Ets-like factors .

In DNA-protein binding studies , we detected the binding of <protein>transcription factors</protein> <protein>GABP alpha and -beta</protein> to a <dna>dyad symmetry element</dna> ( <dna>DSE</dna> ) of the <dna>distal enhancer</dna> , which is formed by <dna>palindromic binding sites</dna> of <protein>Ets-like factors</protein> .


Introduction of point mutations suppressing GABP binding to the DSE interfered with the induction of the distal enhancer and the entire IL-2 promoter-enhancer , while overexpression of both GABP factors enhanced the IL-2 promoter-enhancer induction .

Introduction of point mutations suppressing GABP binding to the <dna>DSE</dna> interfered with the induction of the <dna>distal enhancer</dna> and the entire <dna>IL-2 promoter-enhancer</dna> , while overexpression of both <protein>GABP factors</protein> enhanced the <dna>IL-2 promoter-enhancer</dna> induction .


Overexpression of BXB , a constitutive active version of c-Raf , and of further members of the Ras - Raf - Erk signal cascade exerted an increase of GABP -mediated promoter-enhancer induction .

Overexpression of <protein>BXB</protein> , a constitutive active version of <protein>c-Raf</protein> , and of further members of the <protein>Ras</protein> - <protein>Raf</protein> - <protein>Erk</protein> signal cascade exerted an increase of <protein>GABP</protein> -mediated promoter-enhancer induction .


In conjunction with previously published data on c-Raf -induced phosphorylation of GABP factors ( E.Flory , A. Hoffmeyer , U.Smola , U.R.Rapp , and J.T.Bruder , J.Virol.70 : 2260- 2268 , 1996 ) , these results indicate a contribution of GABP factors to the Raf -mediated enhancement of IL-2 induction during T-cell activation .

In conjunction with previously published data on <protein>c-Raf</protein> -induced phosphorylation of <protein>GABP factors</protein> ( E.Flory , A. Hoffmeyer , U.Smola , U.R.Rapp , and J.T.Bruder , J.Virol.70 : 2260- 2268 , 1996 ) , these results indicate a contribution of <protein>GABP factors</protein> to the <protein>Raf</protein> -mediated enhancement of <protein>IL-2</protein> induction during T-cell activation .


Lipopolysaccharide induction of the tumor necrosis factor-alpha promoter in human monocytic cells .

Lipopolysaccharide induction of the <dna>tumor necrosis factor-alpha promoter</dna> in <cell_type>human monocytic cells</cell_type> .


Regulation by Egr-1 , c-Jun , and NF-kappaB transcription factors .

Regulation by <protein>Egr-1</protein> , <protein>c-Jun</protein> , and <protein>NF-kappaB</protein> <protein>transcription factors</protein> .


Biosynthesis of tumor necrosis factor-alpha ( TNF-alpha ) is predominantly by cells of the monocytic lineage .

Biosynthesis of <protein>tumor necrosis factor-alpha</protein> ( <protein>TNF-alpha</protein> ) is predominantly by cells of the <cell_type>monocytic lineage</cell_type> .


This study examined the role of various cis-acting regulatory elements in the lipopolysaccharide ( LPS ) induction of the human TNF-alpha promoter in cells of monocytic lineage .

This study examined the role of various <dna>cis-acting regulatory elements</dna> in the lipopolysaccharide ( LPS ) induction of the <dna>human TNF-alpha promoter</dna> in cells of <cell_type>monocytic lineage</cell_type> .


Functional analysis of monocytic THP-1 cells transfected with plasmids containing various lengths of TNF-alpha promoter localized enhancer elements in a region ( -182 to -37 base pairs ( bp ) ) that were required for optimal transcription of the TNF-alpha gene in response to LPS .

Functional analysis of <cell_line>monocytic THP-1 cells</cell_line> transfected with <dna>plasmids</dna> containing various lengths of <dna>TNF-alpha promoter</dna> localized <dna>enhancer elements</dna> in a region ( <dna>-182 to -37 base pairs</dna> ( bp ) ) that were required for optimal transcription of the <dna>TNF-alpha gene</dna> in response to LPS .


Two regions were identified : region I ( -182 to -162 bp ) contained an overlapping Sp1/Egr-1 site , and region II ( -119 to -88 ) contained CRE and NF-kappaB ( designated kappaB3 ) sites .

Two regions were identified : <dna>region I</dna> ( <dna>-182 to -162 bp</dna> ) contained an overlapping <dna>Sp1/Egr-1 site</dna> , and <dna>region II</dna> ( <dna>-119 to -88</dna> ) contained <dna>CRE</dna> and <dna>NF-kappaB ( designated kappaB3 ) sites</dna> .


In unstimulated THP-1 , CRE-binding protein and , to a lesser extent , c-Jun complexes were found to bind to the CRE site .

In unstimulated <cell_line>THP-1</cell_line> , <protein>CRE-binding protein</protein> and , to a lesser extent , <protein>c-Jun complexes</protein> were found to bind to the <dna>CRE site</dna> .


LPS stimulation increased the binding of c-Jun-containing complexes .

LPS stimulation increased the binding of <protein>c-Jun-containing complexes</protein> .


In addition , LPS stimulation induced the binding of cognate nuclear factors to the Egr-1 and kappaB3 sites , which were identified as Egr-1 and p50/p65 , respectively .

In addition , LPS stimulation induced the binding of cognate <protein>nuclear factors</protein> to the <dna>Egr-1 and kappaB3 sites</dna> , which were identified as <protein>Egr-1</protein> and <protein>p50/p65</protein> , respectively .


The CRE and kappaB3 sites in region II together conferred strong LPS responsiveness to a heterologous promoter , whereas individually they failed to provide transcriptional activation .

The <dna>CRE and kappaB3 sites</dna> in <dna>region II</dna> together conferred strong LPS responsiveness to a <dna>heterologous promoter</dna> , whereas individually they failed to provide transcriptional activation .


Furthermore , increasing the spacing between the CRE and the kappaB3 sites completely abolished LPS induction , suggesting a cooperative interaction between c-Jun complexes and p50/p65 .

Furthermore , increasing the spacing between the <dna>CRE and the kappaB3 sites</dna> completely abolished LPS induction , suggesting a cooperative interaction between <protein>c-Jun complexes</protein> and <protein>p50/p65</protein> .


These studies indicate that maximal LPS induction of the TNF-alpha promoter is mediated by concerted participation of at least two separate cis-acting regulatory elements .

These studies indicate that maximal LPS induction of the <dna>TNF-alpha promoter</dna> is mediated by concerted participation of at least two separate <dna>cis-acting regulatory elements</dna> .


Rescue by cytokines of apoptotic cell death induced by IL-2 deprivation of human antigen-specific T cell clones .

Rescue by <protein>cytokines</protein> of apoptotic cell death induced by <protein>IL-2</protein> deprivation of <cell_line>human antigen-specific T cell clones</cell_line> .


The control of cell survival and cell death is of central importance in tissues with high cell turnover such as the lymphoid system .


We have examined the effect of cytokines on IL-2 deprivation-induced apoptosis of human antigen-specific T helper clones with different cytokine production profiles .

We have examined the effect of <protein>cytokines</protein> on <protein>IL-2</protein> deprivation-induced apoptosis of <cell_line>human antigen-specific T helper clones</cell_line> with different <protein>cytokine</protein> production profiles .


We found that IL-2 , interferon-alpha ( IFN-alpha ) , and IFN-beta inhibited IL-2 deprivation apoptosis in Th0 , Th1 , and Th2 clones .

We found that <protein>IL-2</protein> , <protein>interferon-alpha</protein> ( <protein>IFN-alpha</protein> ) , and <protein>IFN-beta</protein> inhibited <protein>IL-2</protein> deprivation apoptosis in <cell_line>Th0 , Th1 , and Th2 clones</cell_line> .


We also found that IL-2 protects T cell clones from IL-2 deprivation apoptosis accompanying active proliferation and enhanced expression of P53 , Rb and Bcl-xL proteins .

We also found that <protein>IL-2</protein> protects <cell_line>T cell clones</cell_line> from <protein>IL-2</protein> deprivation apoptosis accompanying active proliferation and enhanced expression of <protein>P53</protein> , <protein>Rb</protein> and <protein>Bcl-xL proteins</protein> .


In contrast , IFN-alpha/beta rescued T cell clones from apoptosis without active proliferation , and expression of apoptosis-associated proteins tested so far was unaffected .

In contrast , <protein>IFN-alpha/beta</protein> rescued <cell_line>T cell clones</cell_line> from apoptosis without active proliferation , and expression of <protein>apoptosis-associated proteins</protein> tested so far was unaffected .


This may be due to the fact that T cells treated with IL-2 contained those located in S + G2/M phases of the cell cycle , whereas the vast majority of T cells treated with IFN-alpha/beta were located in G0/G1 phase .

This may be due to the fact that <cell_type>T cells</cell_type> treated with <protein>IL-2</protein> contained those located in S + G2/M phases of the cell cycle , whereas the vast majority of <cell_type>T cells</cell_type> treated with <protein>IFN-alpha/beta</protein> were located in G0/G1 phase .


IFN-alpha/beta specifically induced tyrosine phosphorylation and translocation into nucleus of signal transducers and activators of transcription ( STAT ) 2 protein in the T cell clones .

<protein>IFN-alpha/beta</protein> specifically induced tyrosine phosphorylation and translocation into nucleus of <protein>signal transducers and activators of transcription ( STAT ) 2 protein</protein> in the <cell_line>T cell clones</cell_line> .


In addition , over-expression of STAT2 by transfection of the cDNA prevented apoptosis of the T cell clones .

In addition , over-expression of <protein>STAT2</protein> by transfection of the cDNA prevented apoptosis of the <cell_line>T cell clones</cell_line> .


Our present study shows that IFN-alpha and -beta mediate anti-apoptotic effect through other pathways than that of IL-2 in growth factor deprivation apoptosis .

Our present study shows that <protein>IFN-alpha and -beta</protein> mediate anti-apoptotic effect through other pathways than that of <protein>IL-2</protein> in growth factor deprivation apoptosis .


Interleukin-10 inhibits interferon-gamma-induced intercellular adhesion molecule-1 gene transcription in human monocytes .

<protein>Interleukin-10</protein> inhibits interferon-gamma-induced <dna>intercellular adhesion molecule-1 gene</dna> transcription in <cell_type>human monocytes</cell_type> .


Interleukin-10 ( IL-10 ) is a potent monocyte regulatory cytokine that inhibits gene expression of proinflammatory mediators .

<protein>Interleukin-10</protein> ( <protein>IL-10</protein> ) is a potent <protein>monocyte regulatory cytokine</protein> that inhibits gene expression of <protein>proinflammatory mediators</protein> .


In this study , we investigated the mechanism by which IL-10 downregulates expression of intercellular adhesion molecule-1 ( ICAM-1 ) on the cell surface of normal human monocytes activated with interferon-gamma ( IFN-gamma ) .

In this study , we investigated the mechanism by which <protein>IL-10</protein> downregulates expression of <protein>intercellular adhesion molecule-1</protein> ( <protein>ICAM-1</protein> ) on the cell surface of <cell_type>normal human monocytes</cell_type> activated with <protein>interferon-gamma</protein> ( <protein>IFN-gamma</protein> ) .


IL-10 inhibition of IFN-gamma -induced ICAM-1 expression was apparent as early as 3 hours and was blocked by an anti-IL-10 antibody but not by an isotype-matched control antibody .

<protein>IL-10</protein> inhibition of <protein>IFN-gamma</protein> -induced <protein>ICAM-1</protein> expression was apparent as early as 3 hours and was blocked by an <protein>anti-IL-10 antibody</protein> but not by an <protein>isotype-matched control antibody</protein> .


Northern blot analysis showed that IL-10 reduced the accumulation of ICAM-1 mRNA in IFN-gamma-stimulated monocytes .

Northern blot analysis showed that <protein>IL-10</protein> reduced the accumulation of <rna>ICAM-1 mRNA</rna> in <cell_line>IFN-gamma-stimulated monocytes</cell_line> .


IL-10 inhibition of ICAM-1 steady-state mRNA was detected at 3 hours and remained at 24 hours .

<protein>IL-10</protein> inhibition of <rna>ICAM-1 steady-state mRNA</rna> was detected at 3 hours and remained at 24 hours .


Nuclear run-on transcription assays showed that IL-10 inhibited the rate of IFN-gamma -induced transcription of the ICAM-1 gene , and mRNA stability studies showed that IL-10 did not alter the half-life of IFN-gamma-induced ICAM-1 message .

Nuclear run-on transcription assays showed that <protein>IL-10</protein> inhibited the rate of <protein>IFN-gamma</protein> -induced transcription of the <dna>ICAM-1 gene</dna> , and mRNA stability studies showed that <protein>IL-10</protein> did not alter the half-life of <rna>IFN-gamma-induced ICAM-1 message</rna> .


Thus , IL-10 inhibits IFN-gamma -induced ICAM-1 expression in monocytes primarily at the level of gene transcription .

Thus , <protein>IL-10</protein> inhibits <protein>IFN-gamma</protein> -induced <protein>ICAM-1</protein> expression in <cell_type>monocytes</cell_type> primarily at the level of gene transcription .


Activation of IFN-gamma-responsive genes requires tyrosine phosphorylation of the transcriptional factor STAT-1alpha ( signal transducer and activator of transcription-1alpha ) .

Activation of <dna>IFN-gamma-responsive genes</dna> requires tyrosine phosphorylation of the transcriptional factor <protein>STAT-1alpha</protein> ( <protein>signal transducer and activator of transcription-1alpha</protein> ) .


However , IL-10 did not affect IFN-gamma -induced tyrosine phosphorylation of STAT-1alpha or alter STAT-1alpha binding to the IFN-gamma response element ( IRE ) in the ICAM-1 promoter .

However , <protein>IL-10</protein> did not affect <protein>IFN-gamma</protein> -induced tyrosine phosphorylation of <protein>STAT-1alpha</protein> or alter <protein>STAT-1alpha</protein> binding to the <dna>IFN-gamma response element</dna> ( <dna>IRE</dna> ) in the <dna>ICAM-1 promoter</dna> .


Instead , IL-10 prevented IFN-gamma -induced binding activity at the NF-kappaB site of the tumor necrosis factor alpha ( TNF-alpha ) -responsive NF-kappaB/C-EBP composite element in the ICAM-1 promoter .

Instead , <protein>IL-10</protein> prevented <protein>IFN-gamma</protein> -induced binding activity at the <protein>NF-kappaB</protein> site of the <dna>tumor necrosis factor alpha ( TNF-alpha ) -responsive NF-kappaB/C-EBP composite element</dna> in the <dna>ICAM-1 promoter</dna> .


These data indicate that IL-10 inhibits IFN-gamma -induced transcription of the ICAM-1 gene by a regulatory mechanism that may involve NF-kappaB .

These data indicate that <protein>IL-10</protein> inhibits <protein>IFN-gamma</protein> -induced transcription of the <dna>ICAM-1 gene</dna> by a regulatory mechanism that may involve <protein>NF-kappaB</protein> .


Specific complex formation between the type II bare lymphocyte syndrome-associated transactivators CIITA and RFX5 .

Specific complex formation between the <protein>type II bare lymphocyte syndrome-associated transactivators</protein> <protein>CIITA</protein> and <protein>RFX5</protein> .


Two of the genes defective in the five complementation groups identified in the class II-negative bare lymphocyte syndrome or corresponding laboratory mutants have been cloned .


One gene encodes a protein , RFX5 , that is a member of the RFX family of DNA binding proteins .

One gene encodes a protein , <protein>RFX5</protein> , that is a member of the <protein>RFX family of DNA binding proteins</protein> .


The other , CIITA , encodes a large protein with a defined acidic transcriptional activation domain ; this protein does not interact with DNA .

The other , <protein>CIITA</protein> , encodes a large protein with a defined <protein>acidic transcriptional activation domain</protein> ; this protein does not interact with DNA .


Expression plasmids encoding regions of RFX5 fused to the GAL4 DNA binding domain activated transcription from a reporter construct containing GAL4 sites in a cotransfection assay in the Raji human B cell line .

<dna>Expression plasmids</dna> encoding regions of <protein>RFX5</protein> fused to the <protein>GAL4 DNA binding domain</protein> activated transcription from a reporter construct containing <dna>GAL4 sites</dna> in a cotransfection assay in the <cell_line>Raji human B cell line</cell_line> .


However , these plasmids produced transcriptional activity in HeLa cells only in conjunction with interferon gamma stimulation , a condition in which expression of both CIITA and class II major histocompatibility complex surface proteins are induced .

However , these <dna>plasmids</dna> produced transcriptional activity in <cell_line>HeLa cells</cell_line> only in conjunction with <protein>interferon gamma</protein> stimulation , a condition in which expression of both <protein>CIITA</protein> and <protein>class II major histocompatibility complex surface proteins</protein> are induced .


Furthermore , these plasmids were not active in RJ2.2.5 , an in vitro mutagenized derivative of Raji in which both copies of CIITA are defective .

Furthermore , these <dna>plasmids</dna> were not active in <cell_line>RJ2.2.5</cell_line> , an in vitro mutagenized derivative of <cell_line>Raji</cell_line> in which both copies of <protein>CIITA</protein> are defective .


Transcriptional activation by the RFX5 fusion protein could be restored in RJ2.2.5 by cotransfection with a CIITA expression plasmid .

Transcriptional activation by the <protein>RFX5 fusion protein</protein> could be restored in <cell_line>RJ2.2.5</cell_line> by cotransfection with a <dna>CIITA expression plasmid</dna> .


Finally , a direct interaction between RFX5 and CIITA was detected with the yeast two-hybrid and far-Western blot assays .

Finally , a direct interaction between <protein>RFX5</protein> and <protein>CIITA</protein> was detected with the yeast two-hybrid and far-Western blot assays .


Thus , RFX5 can activate transcription only in cooperation with CIITA .

Thus , <protein>RFX5</protein> can activate transcription only in cooperation with <protein>CIITA</protein> .


RFX5 and CIITA associate to form a complex capable of activating transcription from class II major histocompatibility complex promoters .

<protein>RFX5</protein> and <protein>CIITA</protein> associate to form a complex capable of activating transcription from <dna>class II major histocompatibility complex promoters</dna> .


In this complex , promoter specificity is determined by the DNA binding domain of RFX5 and the general transcription apparatus is recruited by the acidic activation domain of CIITA .

In this complex , promoter specificity is determined by the DNA binding domain of <protein>RFX5</protein> and the general transcription apparatus is recruited by the <protein>acidic activation domain</protein> of <protein>CIITA</protein> .


Involvement of phosphatidylinositol 3-kinase in NFAT activation in T cells .

Involvement of <protein>phosphatidylinositol 3-kinase</protein> in <protein>NFAT</protein> activation in <cell_type>T cells</cell_type> .


Phosphatidylinositol 3-kinase ( PI3-K ) has been implicated in the regulation of cell proliferation in many cell types .

<protein>Phosphatidylinositol 3-kinase</protein> ( <protein>PI3-K</protein> ) has been implicated in the regulation of cell proliferation in many cell types .


We have previously shown that in T cells the PI3-K inhibitor , wortmannin , interferes with activation of the mitogen-activated kinase , Erk2 , after T cell receptor ( TcR ) stimulation .

We have previously shown that in <cell_type>T cells</cell_type> the <protein>PI3-K</protein> inhibitor , wortmannin , interferes with activation of the <protein>mitogen-activated kinase</protein> , <protein>Erk2</protein> , after <protein>T cell receptor</protein> ( <protein>TcR</protein> ) stimulation .


To further explore the involvement of PI3-K in T cell activation , we created a set of potentially dominant negative PI3-K constructs comprising individual or tandem domains of the regulatory p85 subunit and tested their effect on downstream signaling events like Erk2 activation and transcription from an NFAT ( nuclear factor of activated T cells ) element taken from the interleukin-2 promoter .

To further explore the involvement of <protein>PI3-K</protein> in T cell activation , we created a set of potentially <dna>dominant negative PI3-K constructs</dna> comprising individual or <dna>tandem domains</dna> of the <protein>regulatory p85 subunit</protein> and tested their effect on downstream signaling events like <protein>Erk2</protein> activation and transcription from an <dna>NFAT ( nuclear factor of activated T cells ) element</dna> taken from the <dna>interleukin-2 promoter</dna> .


Following TcR stimulation , activation of Erk2 was only inhibited by a previously described truncated form of p85 that can not bind the catalytic subunit , but not by other constructs of p85 .

Following <protein>TcR</protein> stimulation , activation of <protein>Erk2</protein> was only inhibited by a previously described <protein>truncated form of p85</protein> that can not bind the <protein>catalytic subunit</protein> , but not by other constructs of <protein>p85</protein> .


In contrast , several mutant p85 alleles had dramatic effects on NFAT activation .

In contrast , several mutant <protein>p85</protein> alleles had dramatic effects on <protein>NFAT</protein> activation .


Most interestingly , the N-terminal SH2 domain had an inhibitory effect , whereas a mutant p85 containing only the two SH2 domains enhanced basal NFAT activity in a Ras -dependent manner .

Most interestingly , the <protein>N-terminal SH2 domain</protein> had an inhibitory effect , whereas a <protein>mutant p85</protein> containing only the <protein>two SH2 domains</protein> enhanced basal <protein>NFAT</protein> activity in a <protein>Ras</protein> -dependent manner .


Ionomycin induced synergistic activation of NFAT in cells expressing p85 mutants that contained the C-terminal SH2 domain .

Ionomycin induced synergistic activation of <protein>NFAT</protein> in cells expressing <protein>p85 mutants</protein> that contained the <protein>C-terminal SH2 domain</protein> .


Analysis of phosphotyrosine-containing proteins bound to truncated p85 constructs revealed cooperative binding of the two SH2 domains but no apparent differences between the N- and C- terminal SH2 domains .

Analysis of <protein>phosphotyrosine-containing proteins</protein> bound to truncated <protein>p85 constructs</protein> revealed cooperative binding of the <protein>two SH2 domains</protein> but no apparent differences between the <protein>N- and C- terminal SH2 domains</protein> .


Wortmannin did not interfere with NFAT activation , although it inhibited PI3-K and Erk2 activation in the same experiment .

Wortmannin did not interfere with <protein>NFAT</protein> activation , although it inhibited <protein>PI3-K</protein> and <protein>Erk2</protein> activation in the same experiment .


These results suggest that PI3-K is involved in NFAT activation through a complex adaptor function of its regulatory subunit and that its lipid kinase activity is dispensable for this effect .

These results suggest that <protein>PI3-K</protein> is involved in <protein>NFAT</protein> activation through a complex adaptor function of its <protein>regulatory subunit</protein> and that its <protein>lipid kinase</protein> activity is dispensable for this effect .


Acute leukemia with promyelocytic features in PML/RARalpha transgenic mice .


Acute promyelocytic leukemia ( APL ) is associated with reciprocal chromosomal translocations involving the retinoic acid receptor alpha ( RARalpha ) locus on chromosome 17 .

Acute promyelocytic leukemia ( APL ) is associated with reciprocal chromosomal translocations involving the <dna>retinoic acid receptor alpha ( RARalpha ) locus</dna> on <dna>chromosome 17</dna> .


In the majority of cases , RARalpha translocates and fuses with the promyelocytic leukemia ( PML ) gene located on chromosome 15 .

In the majority of cases , <protein>RARalpha</protein> translocates and fuses with the <dna>promyelocytic leukemia ( PML ) gene</dna> located on <dna>chromosome 15</dna> .


The resulting fusion genes encode the two structurally unique PML/RARalpha and RARalpha/PML fusion proteins as well as aberrant PML gene products , the respective pathogenetic roles of which have not been elucidated .

The resulting <dna>fusion genes</dna> encode the two structurally unique <protein>PML/RARalpha</protein> and <protein>RARalpha/PML fusion proteins</protein> as well as <protein>aberrant PML gene products</protein> , the respective pathogenetic roles of which have not been elucidated .


We have generated transgenic mice in which the PML/RARalpha fusion protein is specifically expressed in the myeloid-promyelocytic lineage .

We have generated transgenic mice in which the <protein>PML/RARalpha fusion protein</protein> is specifically expressed in the <cell_type>myeloid-promyelocytic lineage</cell_type> .


During their first year of life , all the PML/ RARalpha transgenic mice have an abnormal hematopoiesis that can best be described as a myeloproliferative disorder .

During their first year of life , all the PML/ <protein>RARalpha</protein> transgenic mice have an abnormal hematopoiesis that can best be described as a myeloproliferative disorder .


Between 12 and 14 months of age , 10 % of them develop a form of acute leukemia with a differentiation block at the promyelocytic stage that closely mimics human APL even in its response to retinoic acid .


Our results are conclusive in vivo evidence that PML/RARalpha plays a crucial role in the pathogenesis of APL .

Our results are conclusive in vivo evidence that <protein>PML/RARalpha</protein> plays a crucial role in the pathogenesis of APL .


Constitutive and inducible protein/DNA interactions of the interferon-gamma promoter in vivo in [ corrected ] CD45RA and CD45R0 T helper subsets [ published erratum appears in Eur J Immunol 1997 Jul ; 27 ( 7 ) : 1830 ]

Constitutive and inducible protein/DNA interactions of the <dna>interferon-gamma promoter</dna> in vivo in [ corrected ] <cell_type>CD45RA and CD45R0 T helper subsets</cell_type> [ published erratum appears in Eur J Immunol 1997 Jul ; 27 ( 7 ) : 1830 ]


Interferon-gamma ( IFN-gamma ) is a key cytokine of T lymphocytes with major regulatory functions in the immune system .

Interferon-gamma ( <protein>IFN-gamma</protein> ) is a key cytokine of <cell_type>T lymphocytes</cell_type> with major regulatory functions in the immune system .


To determine and compare protein/DNA interactions at the native IFN-gamma locus in T cells , we analyzed the human IFN-gamma promoter by ligation-mediated polymerase chain reaction ( LM-PCR ) techniques .

To determine and compare protein/DNA interactions at the native <protein>IFN-gamma</protein> locus in <cell_type>T cells</cell_type> , we analyzed the <dna>human IFN-gamma promoter</dna> by ligation-mediated polymerase chain reaction ( LM-PCR ) techniques .


Accordingly , Jurkat T cells and primary CD45RA and CD45R0 CD4+ T cell subsets isolated from peripheral blood using immunomagnetic beads were cultured and analyzed by LM-PCR .

Accordingly , <cell_line>Jurkat T cells</cell_line> and <cell_type>primary CD45RA and CD45R0 CD4+ T cell subsets</cell_type> isolated from peripheral blood using immunomagnetic beads were cultured and analyzed by LM-PCR .


Constitutive and inducible protein/DNA interactions of the IFN-gamma promoter in vivo were detected in all T cells tested .

Constitutive and inducible protein/DNA interactions of the <dna>IFN-gamma promoter</dna> in vivo were detected in all <cell_type>T cells</cell_type> tested .


Interestingly , an inducible footprint between -183 and -196 was consistently observed in Jurkat T cells and CD45RA and CD45R0 T helper subsets upon stimulation with phorbol 12-myristate 13-acetate+ phytohemagglutinin ( PMA+ PHA ) that was highly sensitive to treatment with corticosteroids .

Interestingly , an inducible footprint between <dna>-183 and -196</dna> was consistently observed in <cell_line>Jurkat T cells</cell_line> and <cell_type>CD45RA and CD45R0 T helper subsets</cell_type> upon stimulation with phorbol 12-myristate 13-acetate+ <protein>phytohemagglutinin</protein> ( PMA+ <protein>PHA</protein> ) that was highly sensitive to treatment with corticosteroids .


This novel target site , denoted the C-site , was shown by several criteria , including cell distribution studies , stimulation experiments , supershift assays , and cross-competition electrophoretic mobility shift assays to bind the transcription factor AP-1 .

This <dna>novel target site</dna> , denoted the <dna>C-site</dna> , was shown by several criteria , including cell distribution studies , stimulation experiments , supershift assays , and cross-competition electrophoretic mobility shift assays to bind the <protein>transcription factor AP-1</protein> .


Mutation of the C-site that prevented AP-1 binding to this site was sufficient strikingly to reduce inducible promoter activity in primary CD45R0 T cells .

Mutation of the <dna>C-site</dna> that prevented <protein>AP-1</protein> binding to this site was sufficient strikingly to reduce inducible promoter activity in <cell_type>primary CD45R0 T cells</cell_type> .


In summary , the data demonstrate that IFN-gamma gene transcription in primary T cells is regulated in vivo at the level of constitutive and inducible protein/DNA interactions .

In summary , the data demonstrate that <protein>IFN-gamma</protein> gene transcription in <cell_type>primary T cells</cell_type> is regulated in vivo at the level of constitutive and inducible protein/DNA interactions .


We propose a model where basal transcription is maintained by binding of various transcription factors to the IFN-gamma promoter , whereas PMA+ PHA -inducible IFN-gamma transcription in CD45R0 T cells is associated with binding of AP-1 to the C-site .

We propose a model where basal transcription is maintained by binding of various <protein>transcription factors</protein> to the <dna>IFN-gamma promoter</dna> , whereas PMA+ <protein>PHA</protein> -inducible <protein>IFN-gamma</protein> transcription in <cell_type>CD45R0 T cells</cell_type> is associated with binding of <protein>AP-1</protein> to the <dna>C-site</dna> .


Activation domain requirements for disruption of Epstein-Barr virus latency by ZEBRA .

Activation domain requirements for disruption of Epstein-Barr virus latency by <protein>ZEBRA</protein> .


Latent infection of B lymphocytes by Epstein-Barr virus ( EBV ) can be disrupted by expression of the EBV ZEBRA protein .

Latent infection of <cell_type>B lymphocytes</cell_type> by Epstein-Barr virus ( EBV ) can be disrupted by expression of the <protein>EBV ZEBRA protein</protein> .


ZEBRA , a transcriptional activator , initiates the EBV lytic cascade by activating viral gene expression .

<protein>ZEBRA</protein> , a transcriptional activator , initiates the EBV lytic cascade by activating viral gene expression .


ZEBRA is also indispensable for viral replication and binds directly to the EBV lytic origin of replication .

<protein>ZEBRA</protein> is also indispensable for viral replication and binds directly to the EBV lytic origin of replication .


The studies described herein demonstrate that the activation domain .


ZEBRA activation can be replaced by a heterologous acidic , proline-rich , or glutamine-rich activation domain .

<protein>ZEBRA</protein> activation can be replaced by a <protein>heterologous acidic , proline-rich , or glutamine-rich activation domain</protein> .


ZEBRA activation domain swap constructs retain ZEBRA 's native abilities to activate specific EBV promoters , to disrupt EBV latency , and to stimulate replication at the EBV lytic origin .

<protein>ZEBRA</protein> activation domain swap constructs retain <protein>ZEBRA</protein> 's native abilities to activate specific <dna>EBV promoters</dna> , to disrupt EBV latency , and to stimulate replication at the <dna>EBV lytic origin</dna> .


Additional work , employing sequential and internal deletions of ZEBRA 's N-terminal activation domain , indicates that its separate activities are not attributable to specific subdomains but are spread throughout its N terminus and therefore can not be inactivated by deleting localized regions .

Additional work , employing sequential and internal deletions of <protein>ZEBRA</protein> 's <protein>N-terminal activation domain</protein> , indicates that its separate activities are not attributable to specific <protein>subdomains</protein> but are spread throughout its <protein>N terminus</protein> and therefore can not be inactivated by deleting localized regions .


CholecystokininB receptor from human Jurkat lymphoblastic T cells is involved in activator protein-1 -responsive gene activation .

<protein>CholecystokininB receptor</protein> from <cell_line>human Jurkat lymphoblastic T cells</cell_line> is involved in <protein>activator protein-1</protein> -responsive gene activation .


The aim of this study was to analyze the role of cholecystokinin ( CCK ( B ) ) receptor in human lymphoblastic Jurkat T cells .

The aim of this study was to analyze the role of <protein>cholecystokinin ( CCK ( B ) ) receptor</protein> in <cell_line>human lymphoblastic Jurkat T cells</cell_line> .


We investigated the trophic effect resulting from activation of such a receptor by using the reporter gene strategy .

We investigated the trophic effect resulting from activation of such a receptor by using the <dna>reporter gene</dna> strategy .


For this purpose , we transiently transfected Jurkat T cells with the reporter plasmid p [ ( TRE ) 3-tk-Luc ] and found that CCK-8 was able to dose-dependently induce luciferase expression related to activator protein-1 ( AP-1 ) activation with a maximal response identical to that obtained with compounds known to activate AP-1 complex ( quantitatively , the same level of induction was obtained with 1 nM 12-O-tetradecanoylphorbol-13-acetate , 100 microM diacylglycerol , or 4 nM epidermal growth factor ) .

For this purpose , we transiently transfected <cell_line>Jurkat T cells</cell_line> with the <dna>reporter plasmid p [ ( TRE ) 3-tk-Luc ]</dna> and found that CCK-8 was able to dose-dependently induce <protein>luciferase</protein> expression related to <protein>activator protein-1</protein> ( <protein>AP-1</protein> ) activation with a maximal response identical to that obtained with compounds known to activate <protein>AP-1 complex</protein> ( quantitatively , the same level of induction was obtained with 1 nM 12-O-tetradecanoylphorbol-13-acetate , 100 microM diacylglycerol , or 4 nM epidermal growth factor ) .


The involvement of the CCK ( B ) receptor in such a stimulation was demonstrated by the inhibiting effect of the selective CCK ( B ) receptor antagonist PD-135 , 158 .

The involvement of the <protein>CCK ( B ) receptor</protein> in such a stimulation was demonstrated by the inhibiting effect of the selective <protein>CCK ( B ) receptor</protein> antagonist PD-135 , 158 .


This effect was confirmed in COS-7 cells transfected with the cDNA of CCK ( B ) receptor cloned from Jurkat T cells .

This effect was confirmed in COS-7 cells transfected with the cDNA of <protein>CCK ( B ) receptor</protein> cloned from <cell_line>Jurkat T cells</cell_line> .


To better understand the AP-1 -dependent luciferase expression in Jurkat T cells , we tested two specific inhibitors of serine/threonine phosphatases-1 and -2A : okadaic acid and calyculin A .

To better understand the <protein>AP-1</protein> -dependent <protein>luciferase</protein> expression in <cell_line>Jurkat T cells</cell_line> , we tested two specific inhibitors of <protein>serine/threonine phosphatases-1 and -2A</protein> : okadaic acid and calyculin A .


These compounds strongly increased the phorbol-12-myristate-13-acetate response , whereas we have not observed a contribution of phosphatase inhibitors on a CCK-8-induced luciferase activity .

These compounds strongly increased the phorbol-12-myristate-13-acetate response , whereas we have not observed a contribution of phosphatase inhibitors on a CCK-8-induced <protein>luciferase</protein> activity .


To confirm that CCK ( B ) receptors are involved in AP-1 response , we investigated the CCK-8 effect on interleukin-2 expression , a natural endogenous gene regulated by several factors , including AP-1 .

To confirm that <protein>CCK ( B ) receptors</protein> are involved in <protein>AP-1</protein> response , we investigated the CCK-8 effect on <protein>interleukin-2</protein> expression , a natural <dna>endogenous gene</dna> regulated by several factors , including <protein>AP-1</protein> .


In Jurkat T cells activated by phorbol-12-myristate-13-acetate and phytohemagglutinin , CCK-8 induced IL-2 expression .

In <cell_line>Jurkat T cells</cell_line> activated by phorbol-12-myristate-13-acetate and <protein>phytohemagglutinin</protein> , CCK-8 induced IL-2 expression .


This induction was abolished by PD-135 , 158 .


Our results indicate that CCK-8 exerts a trophic effect in Jurkat T cells through stimulation of CCK ( B ) receptors by modulation of expression of AP-1-regulated genes .

Our results indicate that CCK-8 exerts a trophic effect in <cell_line>Jurkat T cells</cell_line> through stimulation of <protein>CCK ( B ) receptors</protein> by modulation of expression of <dna>AP-1-regulated genes</dna> .


A conserved tissue-specific structure at a human T-cell receptor beta-chain core promoter .

A conserved tissue-specific structure at a <dna>human T-cell receptor beta-chain core promoter</dna> .


The T-cell receptor ( TCR ) beta-chain promoters have been characterized as nonstructured basal promoters that carry a single conserved ubiquitous cyclic AMP-responsive element .

The <dna>T-cell receptor ( TCR ) beta-chain promoters</dna> have been characterized as <dna>nonstructured basal promoters</dna> that carry a single conserved <dna>ubiquitous cyclic AMP-responsive element</dna> .


Our investigation of the human TCR beta gene uncovers a surprisingly complex and tissue-specific structure at the TCR Vbeta 8.1 promoter .

Our investigation of the <dna>human TCR beta gene</dna> uncovers a surprisingly complex and tissue-specific structure at the <dna>TCR Vbeta 8.1 promoter</dna> .


The core of the promoter ( positions -42 to +11 ) is recognized by the lymphoid cell-specific transcription factors Ets-1 , LEF1 , and AML1 as well as by CREB/ATF-1 , as is demonstrated in gel shift and footprinting experiments .

The core of the <dna>promoter</dna> ( <dna>positions -42 to +11</dna> ) is recognized by the <protein>lymphoid cell-specific transcription factors</protein> <protein>Ets-1</protein> , <protein>LEF1</protein> , and <protein>AML1</protein> as well as by <protein>CREB/ATF-1</protein> , as is demonstrated in gel shift and footprinting experiments .


With the exception of LEF1 , these factors activate transcription in T cells .

With the exception of <protein>LEF1</protein> , these factors activate transcription in <cell_type>T cells</cell_type> .


Binding sites at the core region show little conservation with consensus sites .

<dna>Binding sites</dna> at the core region show little conservation with <dna>consensus sites</dna> .


Nonetheless , CREB , Ets-1 , and AML1 bind and activate cooperatively and very efficiently through the nonconsensus binding sites at the core promoter region .

Nonetheless , <protein>CREB</protein> , <protein>Ets-1</protein> , and <protein>AML1</protein> bind and activate cooperatively and very efficiently through the <dna>nonconsensus binding sites</dna> at the <dna>core promoter region</dna> .


Moderate ubiquitous activation is further induced by CREB/ATF and Sp1 factors through proximal upstream elements .

Moderate ubiquitous activation is further induced by <protein>CREB/ATF and Sp1 factors</protein> through <dna>proximal upstream elements</dna> .


The tissue-specific core promoter structure is apparently conserved in other T-cell-specifically expressed genes such as the CD4 gene .

The <dna>tissue-specific core promoter structure</dna> is apparently conserved in other <dna>T-cell-specifically expressed genes</dna> such as the <dna>CD4 gene</dna> .


Our observations suggest that both the enhancer and the promoter have a complex tissue-specific structure whose functional interplay potentiates T-cell-specific transcription .

Our observations suggest that both the <dna>enhancer</dna> and the <dna>promoter</dna> have a complex tissue-specific structure whose functional interplay potentiates T-cell-specific transcription .


The cytoplasmic domain of granulocyte-macrophage colony-stimulating factor ( GM-CSF ) receptor alpha subunit is essential for both GM-CSF -mediated growth and differentiation .

The <protein>cytoplasmic domain</protein> of <protein>granulocyte-macrophage colony-stimulating factor ( GM-CSF ) receptor alpha subunit</protein> is essential for both <protein>GM-CSF</protein> -mediated growth and differentiation .


Granulocyte-macrophage colony-stimulating factor ( GM-CSF ) regulates differentiation , survival , and proliferation of colony-forming unit-granulocyte-macrophage progenitor cells .

<protein>Granulocyte-macrophage colony-stimulating factor</protein> ( <protein>GM-CSF</protein> ) regulates differentiation , survival , and proliferation of <cell_line>colony-forming unit-granulocyte-macrophage progenitor cells</cell_line> .


The biologic actions of GM-CSF are mediated by binding to a specific receptor consisting of two chains designated as alpha and beta subunits .

The biologic actions of <protein>GM-CSF</protein> are mediated by binding to a specific receptor consisting of two chains designated as <protein>alpha and beta subunits</protein> .


We have demonstrated that the murine FDC-P1-derived cell line WT-19 transfected with the human GM-CSF receptor alpha and beta subunits ( GM-CSFRalpha and beta ) can be induced to differentiate by the addition of human GM-CSF ( hGM-CSF ) .

We have demonstrated that the <cell_line>murine FDC-P1-derived cell line</cell_line> <cell_line>WT-19</cell_line> transfected with the <protein>human GM-CSF receptor alpha and beta subunits</protein> ( <protein>GM-CSFRalpha and beta</protein> ) can be induced to differentiate by the addition of <protein>human GM-CSF</protein> ( <protein>hGM-CSF</protein> ) .


By expressing a series of GM-CSFRalpha mutants in WT19 cells , we have determined the amino acid domains of the GM-CSFRalpha cytoplasmic domain that regulate cell differentiation , proliferation , and survival .

By expressing a series of <protein>GM-CSFRalpha mutants</protein> in <cell_line>WT19 cells</cell_line> , we have determined the <protein>amino acid domains</protein> of the <protein>GM-CSFRalpha</protein> <protein>cytoplasmic domain</protein> that regulate cell differentiation , proliferation , and survival .


We found that the membrane proximal proline-rich domain and adjacent 16 residues are essential for both hGM-CSF -dependent cell proliferation and differentiation .

We found that the <protein>membrane proximal proline-rich domain</protein> and <protein>adjacent 16 residues</protein> are essential for both <protein>hGM-CSF</protein> -dependent cell proliferation and differentiation .


In contrast , the C-terminal region of the GM-CSFRalpha cytoplasmic domain was not necessary for cell differentiation mediated by hGM-CSF , but the removal of this region severely impaired the ability of hGM-CSF to support cell survival .

In contrast , the <protein>C-terminal region</protein> of the <protein>GM-CSFRalpha cytoplasmic domain</protein> was not necessary for cell differentiation mediated by <protein>hGM-CSF</protein> , but the removal of this region severely impaired the ability of <protein>hGM-CSF</protein> to support cell survival .


While the activation of JAK2 , Shc , Erk , and STAT5 proteins correlated with hGM-CSF -mediated cell growth , cellular differentiation occurred in the absence of activation of these signal transduction pathways .

While the activation of <protein>JAK2</protein> , <protein>Shc</protein> , <protein>Erk</protein> , and <protein>STAT5 proteins</protein> correlated with <protein>hGM-CSF</protein> -mediated cell growth , cellular differentiation occurred in the absence of activation of these signal transduction pathways .


gamma-Interferon -induced resistance to 1 , 25- ( OH ) 2 D3 in human monocytes and macrophages : a mechanism for the hypercalcemia of various granulomatoses .

<protein>gamma-Interferon</protein> -induced resistance to 1 , 25- ( OH ) 2 D3 in <cell_type>human monocytes</cell_type> and <cell_type>macrophages</cell_type> : a mechanism for the hypercalcemia of various granulomatoses .


The hypercalcemia of various granulomatoses is caused by endogenous 1 , 25-dihydroxyvitamin D [ 1 , 25- ( OH ) 2D3 ] overproduction by disease-activated macrophages .

The hypercalcemia of various granulomatoses is caused by endogenous 1 , 25-dihydroxyvitamin D [ 1 , 25- ( OH ) 2D3 ] overproduction by disease-activated <cell_type>macrophages</cell_type> .


The inability of 1 , 25 ( OH ) 2D3 to suppress its synthesis in macrophages contrasts with the tight control of its production in macrophage precursors , peripheral blood monocytes ( PBM ) .

The inability of 1 , 25 ( OH ) 2D3 to suppress its synthesis in <cell_type>macrophages</cell_type> contrasts with the tight control of its production in macrophage precursors , <cell_type>peripheral blood monocytes</cell_type> ( <cell_type>PBM</cell_type> ) .


We examined whether 1 , 25 ( OH ) 2D3 resistance develops as PBM differentiate to macrophages or with macrophage activation .

We examined whether 1 , 25 ( OH ) 2D3 resistance develops as <cell_type>PBM</cell_type> differentiate to <cell_type>macrophages</cell_type> or with macrophage activation .


Normal human pulmonary alveolar macrophages ( PAM ) are less sensitive to 1 , 25 ( OH ) 2D3 than PBM , despite similar vitamin D receptor content ; however , both PBM and PAM respond to exogenous 1 , 25- ( OH ) 2D3 by inhibiting 1 , 25 ( OH ) 2D3 synthesis and inducing 1 , 25 ( OH ) 2D3 degradation through enhancement of 24-hydroxylase mRNA levels and activity .

Normal <cell_type>human pulmonary alveolar macrophages</cell_type> ( <cell_type>PAM</cell_type> ) are less sensitive to 1 , 25 ( OH ) 2D3 than <cell_type>PBM</cell_type> , despite similar <protein>vitamin D receptor</protein> content ; however , both <cell_type>PBM</cell_type> and <cell_type>PAM</cell_type> respond to exogenous 1 , 25- ( OH ) 2D3 by inhibiting 1 , 25 ( OH ) 2D3 synthesis and inducing 1 , 25 ( OH ) 2D3 degradation through enhancement of <protein>24-hydroxylase</protein> mRNA levels and activity .


The human monocytic cell line THP-1 mimics PAM in 1 , 25 ( OH ) 2D3 synthesis and sensitivity to exogenous 1 , 25 ( OH ) 2D3 .

The <cell_line>human monocytic cell line</cell_line> <cell_line>THP-1</cell_line> mimics <cell_type>PAM</cell_type> in 1 , 25 ( OH ) 2D3 synthesis and sensitivity to exogenous 1 , 25 ( OH ) 2D3 .


We utilized THP-1 cells to examine the response to 1 , 25 ( OH ) 2D3 with macrophage activation .

We utilized <cell_line>THP-1 cells</cell_line> to examine the response to 1 , 25 ( OH ) 2D3 with macrophage activation .


Activation of THP-1 cells with gamma-interferon ( gamma-IFN ) enhances 1 , 25 ( OH ) 2D3 synthesis 30-fold , blocks 1 , 25- ( OH ) 2D3 suppression of its synthesis , and reduces by 42.2 % 1 , 25- ( OH ) 2D3 induction of its degradation .

Activation of <cell_line>THP-1 cells</cell_line> with <protein>gamma-interferon</protein> ( <protein>gamma-IFN</protein> ) enhances 1 , 25 ( OH ) 2D3 synthesis 30-fold , blocks 1 , 25- ( OH ) 2D3 suppression of its synthesis , and reduces by 42.2 % 1 , 25- ( OH ) 2D3 induction of its degradation .


The antagonistic effects of gamma-IFN are not merely restricted to enzymatic activities .

The antagonistic effects of <protein>gamma-IFN</protein> are not merely restricted to enzymatic activities .


In THP-1 cells and in normal PBM , gamma-IFN inhibits 1 , 25- ( OH ) 2D3 induction of 24-hydroxylase mRNA levels without reducing mRNA stability , suggesting gamma-IFN inhibition of 1 , 25 ( OH ) 2D3 transactivating function .

In <cell_line>THP-1 cells</cell_line> and in normal <cell_type>PBM</cell_type> , <protein>gamma-IFN</protein> inhibits 1 , 25- ( OH ) 2D3 induction of <protein>24-hydroxylase</protein> mRNA levels without reducing mRNA stability , suggesting <protein>gamma-IFN</protein> inhibition of 1 , 25 ( OH ) 2D3 transactivating function .


These results explain 1 , 25 ( OH ) 2D3 overproduction in granulomatoses and demonstrate potent inhibition by gamma-IFN of 1 , 25 ( OH ) 2D3 action in immune cells .

These results explain 1 , 25 ( OH ) 2D3 overproduction in granulomatoses and demonstrate potent inhibition by <protein>gamma-IFN</protein> of 1 , 25 ( OH ) 2D3 action in <cell_type>immune cells</cell_type> .


Molecular cloning and characterization of a cDNA , CHEMR1 , encoding a chemokine receptor with a homology to the human C-C chemokine receptor , CCR-4 .

Molecular cloning and characterization of a <dna>cDNA</dna> , <dna>CHEMR1</dna> , encoding a <protein>chemokine receptor</protein> with a homology to the <protein>human C-C chemokine receptor</protein> , <protein>CCR-4</protein> .


Chemokines refer to a rapidly expanding family of small cytokines whose primary function is recruitment of leukocytes to inflammatory sites .

<protein>Chemokines</protein> refer to a rapidly expanding family of small <protein>cytokines</protein> whose primary function is recruitment of leukocytes to inflammatory sites .


These are known to bind to seven-transmembrane-domain containing receptors .

These are known to bind to <protein>seven-transmembrane-domain containing receptors</protein> .


A cDNA clone , CHEMR1 , resembling the typical G protein-coupled receptor , was isolated from a mouse cytotoxic T-lymphocyte ( CTL ) library .

A <dna>cDNA clone</dna> , <dna>CHEMR1</dna> , resembling the typical <protein>G protein-coupled receptor</protein> , was isolated from a <dna>mouse cytotoxic T-lymphocyte ( CTL ) library</dna> .


Northern blot analysis in mouse cell lines suggests that its expression is found in a variety of cells , including T cells , B cells , and macrophages .

Northern blot analysis in mouse cell lines suggests that its expression is found in a variety of cells , including <cell_type>T cells</cell_type> , <cell_type>B cells</cell_type> , and <cell_type>macrophages</cell_type> .


The CHEMR1 gene Scya3r2 is a single-copy gene whose open reading frame may be in a single exon and maps to the distal region of mouse Chr 9 where the mouse macrophage inflammatory protein-1alpha ( MIP-1alpha ) receptor gene Scya3r and two related C-C chemokine receptor-like genes reside .

The <dna>CHEMR1 gene</dna> <dna>Scya3r2</dna> is a <dna>single-copy gene</dna> whose open reading frame may be in a single exon and maps to the distal region of <dna>mouse Chr 9</dna> where the <dna>mouse macrophage inflammatory protein-1alpha ( MIP-1alpha ) receptor gene</dna> <dna>Scya3r</dna> and two related <dna>C-C chemokine receptor-like genes</dna> reside .


Amino acid sequence comparison shows that CHEMR1 is 84 % identical to human CCR-4 , indicating that CHEMR1 is likely to be a mouse CCR-4 .

Amino acid sequence comparison shows that <dna>CHEMR1</dna> is 84 % identical to <protein>human CCR-4</protein> , indicating that <dna>CHEMR1</dna> is likely to be a <protein>mouse CCR-4</protein> .


Binding assays using 125I-labeled C-C chemokines in mammalian cells indicated that CHEMR1 did not bind MIP-1alpha , RANTES , or MIP-1beta , whereas CCR-1 binds MIP-1alpha and RANTES .

Binding assays using <protein>125I-labeled C-C chemokines</protein> in <cell_type>mammalian cells</cell_type> indicated that <dna>CHEMR1</dna> did not bind MIP-1alpha , RANTES , or MIP-1beta , whereas <protein>CCR-1</protein> binds <protein>MIP-1alpha</protein> and <protein>RANTES</protein> .


Our result is different from the reported properties of human CCR-4 .

Our result is different from the reported properties of <protein>human CCR-4</protein> .


This suggests that CHEMR1 may be a receptor for unidentified C-C chemokine or a low-affinity receptor for MIP-1alpha .

This suggests that <dna>CHEMR1</dna> may be a receptor for unidentified <protein>C-C chemokine</protein> or a low-affinity receptor for <protein>MIP-1alpha</protein> .


Transactivation by CIITA , the type II bare lymphocyte syndrome-associated factor , requires participation of multiple regions of the TATA box binding protein .

Transactivation by <protein>CIITA</protein> , the <protein>type II bare lymphocyte syndrome-associated factor</protein> , requires participation of multiple regions of the <protein>TATA box binding protein</protein> .


CIITA is a positive regulator of class II major histocompatibility complex gene transcription that has been found to be defective in one of the five complementation groups of class II major histocompatibility complex-negative cell lines .

<protein>CIITA</protein> is a positive regulator of <dna>class II major histocompatibility complex gene</dna> transcription that has been found to be defective in one of the five complementation groups of <cell_line>class II major histocompatibility complex-negative cell lines</cell_line> .


Its N-terminal region is capable of activating transcription from a reporter gene when fused to a DNA binding domain .

Its <protein>N-terminal region</protein> is capable of activating transcription from a reporter gene when fused to a <protein>DNA binding domain</protein> .


We have investigated the mechanism of transactivation mediated by the CIITA activation domain by studying its role in the process of transcription initiation and elongation .

We have investigated the mechanism of transactivation mediated by the <protein>CIITA activation domain</protein> by studying its role in the process of transcription initiation and elongation .


Specifically the altered specificity TBP ( TATA box binding protein ) assay has been used to analyze the response of the CIITA activation domain to mutations in TBP known to disrupt its interaction with its associated general factors .

Specifically the altered specificity TBP ( <protein>TATA box binding protein</protein> ) assay has been used to analyze the response of the <protein>CIITA activation domain</protein> to mutations in <protein>TBP</protein> known to disrupt its interaction with its <protein>associated general factors</protein> .


Transactivation by CIITA was extremely sensitive to a mutation in TBP that in yeast is known to abolish VP16 -mediated transcription but leaves basal transcription unaffected .

Transactivation by <protein>CIITA</protein> was extremely sensitive to a mutation in <protein>TBP</protein> that in yeast is known to abolish <protein>VP16</protein> -mediated transcription but leaves basal transcription unaffected .


A TBP mutant defective in interaction with TBP-associated factor TAFII250 also failed to mediate transactivation through the CIITA activation domain .

A TBP mutant defective in interaction with <protein>TBP-associated factor</protein> <protein>TAFII250</protein> also failed to mediate transactivation through the <protein>CIITA activation domain</protein> .


Certain interactions between TBP and general factors that are specifically required for acidic activation domains were also required for CIITA -mediated transactivation to reach its full potential .

Certain interactions between <protein>TBP</protein> and <protein>general factors</protein> that are specifically required for <protein>acidic activation domains</protein> were also required for <protein>CIITA</protein> -mediated transactivation to reach its full potential .


Finally , like VP16 , CIITA was able to stimulate elongation of transcription .

Finally , like VP16 , <protein>CIITA</protein> was able to stimulate elongation of transcription .


Overall the mechanism of transactivation by the human B-cell-specific CIITA is very similar to that mediated by the herpes virus transactivator VP16 in the ways that have been tested .

Overall the mechanism of transactivation by the <protein>human B-cell-specific CIITA</protein> is very similar to that mediated by the <protein>herpes virus transactivator</protein> <protein>VP16</protein> in the ways that have been tested .


Relief of cyclin A gene transcriptional inhibition during activation of human primary T lymphocytes via CD2 and CD28 adhesion molecules .

Relief of <protein>cyclin A</protein> gene transcriptional inhibition during activation of <cell_type>human primary T lymphocytes</cell_type> via <protein>CD2</protein> and <protein>CD28</protein> <protein>adhesion molecules</protein> .


Cyclin A transcription is cell cycle regulated and induced by cell proliferative signals .

<protein>Cyclin A</protein> transcription is cell cycle regulated and induced by cell proliferative signals .


To understand the mechanisms underlined in this regulation in normal human cells , we have analysed in vivo protein-DNA interactions at the Cyclin A locus in primary T lymphocytes .

To understand the mechanisms underlined in this regulation in normal human cells , we have analysed in vivo protein-DNA interactions at the <protein>Cyclin A</protein> locus in <cell_type>primary T lymphocytes</cell_type> .


Stimulation of purified T lymphocytes by a combination of monoclonal antibodies directed at CD2 and CD28 adhesion molecules gives rise to a long lasting proliferation in the absence of accessory cells .

Stimulation of purified T lymphocytes by a combination of <protein>monoclonal antibodies</protein> directed at <protein>CD2</protein> and <protein>CD28</protein> <protein>adhesion molecules</protein> gives rise to a long lasting proliferation in the absence of <cell_type>accessory cells</cell_type> .


Cyclin A was observed after 4 days of costimulation with anti CD2 + CD28 whereas stimulation by anti CD2 or anti CD28 alone was not effective .

<protein>Cyclin A</protein> was observed after 4 days of costimulation with <protein>anti CD2</protein> + <protein>CD28</protein> whereas stimulation by <protein>anti CD2</protein> or <protein>anti CD28</protein> alone was not effective .


In vivo genomic DMS footprinting revealed upstream of the major transcription initiation sites , the presence of at least three protein binding sites , two of which were constitutively occupied .

In vivo genomic DMS footprinting revealed upstream of the major <dna>transcription initiation sites</dna> , the presence of at least three <dna>protein binding sites</dna> , two of which were constitutively occupied .


They bind in vitro respectively ATF-1 and NF-Y proteins .

They bind in vitro respectively <protein>ATF-1</protein> and <protein>NF-Y proteins</protein> .


The third site was occupied in quiescent cells or in cells stimulated by anti CD2 or anti CD28 alone .

The third site was occupied in quiescent cells or in cells stimulated by <protein>anti CD2</protein> or <protein>anti CD28</protein> alone .


The mitogenic combination of anti CD2 + anti CD28 released the footprint as cells were committed to proliferation .

The mitogenic combination of <protein>anti CD2</protein> + <protein>anti CD28</protein> released the footprint as cells were committed to proliferation .


Consistent with theses results , nuclear extracts prepared from quiescent cells formed a specific complex with this element , whereas extracts prepared from cells treated with anti CD2 + anti CD28 failed to do so after cells entered a proliferative state .

Consistent with theses results , nuclear extracts prepared from quiescent cells formed a specific complex with this element , whereas extracts prepared from cells treated with <protein>anti CD2</protein> + <protein>anti CD28</protein> failed to do so after cells entered a proliferative state .


An enhancer-blocking element between alpha and delta gene segments within the human T cell receptor alpha/delta locus .

An <dna>enhancer-blocking element</dna> between <dna>alpha and delta gene segments</dna> within the <dna>human T cell receptor alpha/delta locus</dna> .


T cell receptor ( TCR ) alpha and delta gene segments are organized within a single genetic locus but are differentially regulated during T cell development .

<protein>T cell receptor ( TCR ) alpha</protein> and delta gene segments are organized within a single genetic locus but are differentially regulated during T cell development .


An enhancer-blocking element ( BEAD-1 , for blocking element alpha/delta 1 ) was localized to a 2.0-kb region 3 ' of TCR delta gene segments and 5 ' of TCR alpha joining gene segments within this locus .

An <dna>enhancer-blocking element</dna> ( <dna>BEAD-1</dna> , for blocking <dna>element alpha/delta 1</dna> ) was localized to a <dna>2.0-kb region</dna> 3 ' of <dna>TCR delta gene segments</dna> and 5 ' of <dna>TCR alpha joining gene segments</dna> within this locus .


BEAD-1 blocked the ability of the TCR delta enhancer ( Edelta ) to activate a promoter when located between the two in a chromatin-integrated construct .

<dna>BEAD-1</dna> blocked the ability of the <dna>TCR delta enhancer</dna> ( <dna>Edelta</dna> ) to activate a promoter when located between the two in a <dna>chromatin-integrated construct</dna> .


We propose that BEAD-1 functions as a boundary that separates the TCR alpha/delta locus into distinct regulatory domains controlled by Edelta and the TCR alpha enhancer , and that it prevents Edelta from opening the chromatin of the TCR alpha joining gene segments for VDJ recombination at an early stage of T cell development .

We propose that <dna>BEAD-1</dna> functions as a boundary that separates the <dna>TCR alpha/delta locus</dna> into distinct <dna>regulatory domains</dna> controlled by <dna>Edelta</dna> and the <dna>TCR alpha enhancer</dna> , and that it prevents <dna>Edelta</dna> from opening the <dna>chromatin</dna> of the <dna>TCR alpha</dna> joining gene segments for VDJ recombination at an early stage of T cell development .


Uncoupling of cell cycle arrest from the expression of monocytic differentiation markers in HL60 cell variants .

Uncoupling of cell cycle arrest from the expression of monocytic differentiation markers in <cell_line>HL60 cell variants</cell_line> .


Differentiation generally leads to cell cycle arrest .


Human leukemia HL60 cells respond to the presence of 1 , 25-dihydroxyvitamin D3 ( 1 , 25D3 ) by expressing a number of markers of the monocyte/macrophage phenotype and become arrested predominantly in the G1 phase of the cell cycle .

<cell_line>Human leukemia HL60 cells</cell_line> respond to the presence of 1 , 25-dihydroxyvitamin D3 ( 1 , 25D3 ) by expressing a number of markers of the monocyte/macrophage phenotype and become arrested predominantly in the G1 phase of the cell cycle .


We have recently reported a series ( A ) of 1 , 25D3-resistant variants of HL60 cells which proliferate in the presence of 1 , 25D3 and do not express differentiation markers ( Exp. Cell Res. 224 , 312 , 1996 ) .

We have recently reported a series ( A ) of 1 , 25D3-resistant variants of <cell_line>HL60 cells</cell_line> which proliferate in the presence of 1 , 25D3 and do not express differentiation markers ( Exp. Cell Res. 224 , 312 , 1996 ) .