The presence of an active CRE site in the bcl-2 promoter implies that the regulation of bcl-2 expression is linked to a signal transduction pathway in B cells .

The presence of an active <dna>CRE site</dna> in the <dna>bcl-2 promoter</dna> implies that the regulation of <protein>bcl-2</protein> expression is linked to a signal transduction pathway in <cell_type>B cells</cell_type> .


Treatment of the mature B-cell line BAL-17 with either anti-immunoglobulin M or phorbol 12-myristate 13-acetate leads to an increase in bcl-2 expression that is mediated by the CRE site .

Treatment of the <cell_line>mature B-cell line BAL-17</cell_line> with either anti-immunoglobulin M or phorbol 12-myristate 13-acetate leads to an increase in <protein>bcl-2</protein> expression that is mediated by the <dna>CRE site</dna> .


Treatment of the more immature B-cell line , Ramos , with phorbol esters rescues the cells from calcium-dependent apoptosis .

Treatment of the more <cell_line>immature B-cell line</cell_line> , <cell_line>Ramos</cell_line> , with phorbol esters rescues the cells from calcium-dependent apoptosis .


bcl-2 expression is increased following phorbol ester treatment , and the increased expression is dependent on the CRE site .

<protein>bcl-2</protein> expression is increased following phorbol ester treatment , and the increased expression is dependent on the <dna>CRE site</dna> .


These stimuli result in phosphorylation of CREB at serine 133 .

These stimuli result in phosphorylation of <protein>CREB</protein> at serine 133 .


The phosphorylation of CREB that results in activation is mediated by protein kinase C rather than by protein kinase A .

The phosphorylation of <protein>CREB</protein> that results in activation is mediated by <protein>protein kinase C</protein> rather than by <protein>protein kinase A</protein> .


Although the CRE site is necessary , optimal induction of bcl-2 expression requires participation of the upstream regulatory element , suggesting that phosphorylation of CREB alters its interaction with the upstream regulatory element .

Although the <dna>CRE site</dna> is necessary , optimal induction of <protein>bcl-2</protein> expression requires participation of the <dna>upstream regulatory element</dna> , suggesting that phosphorylation of <protein>CREB</protein> alters its interaction with the <dna>upstream regulatory element</dna> .


The CRE site in the bcl-2 promoter appears to play a major role in the induction of bcl-2 expression during the activation of mature B cells and during the rescue of immature B cells from apoptosis .

The <dna>CRE site</dna> in the <dna>bcl-2 promoter</dna> appears to play a major role in the induction of <protein>bcl-2</protein> expression during the activation of <cell_type>mature B cells</cell_type> and during the rescue of <cell_type>immature B cells</cell_type> from apoptosis .


It is possible that the CRE site is responsible for induction of bcl-2 expression in other cell types , particularly those in which protein kinase C is involved .

It is possible that the <dna>CRE site</dna> is responsible for induction of <protein>bcl-2</protein> expression in other cell types , particularly those in which <protein>protein kinase C</protein> is involved .


Characterization of the human myeloid cell nuclear differentiation antigen gene promoter .

Characterization of the <dna>human myeloid cell nuclear differentiation antigen gene promoter</dna> .


MNDA ( myeloid cell nuclear differentiation antigen ) is an interferon alpha regulated nuclear protein expressed only in cells of the human myelomonocytic lineage .

<protein>MNDA</protein> ( <protein>myeloid cell nuclear differentiation antigen</protein> ) is an <protein>interferon alpha regulated nuclear protein</protein> expressed only in cells of the <cell_type>human myelomonocytic lineage</cell_type> .


To identify mechanisms responsible for this lineage-specific and interferon-regulated expression , the 5 ' flanking sequence of the gene has been characterized .

To identify mechanisms responsible for this lineage-specific and interferon-regulated expression , the <dna>5 ' flanking sequence</dna> of the gene has been characterized .


Two interferon-stimulated response elements ( ISRE ) flank a multiple transcription start site region identifying MNDA as a TATA-less interferon-regulated gene .

Two <dna>interferon-stimulated response elements</dna> ( <dna>ISRE</dna> ) flank a multiple transcription start site region identifying <protein>MNDA</protein> as a <dna>TATA-less interferon-regulated gene</dna> .


Other DNA elements present include a cluster of Myb sites , several Ets , an Ets related PU.1 site and an Sp1 site located within 600 bp of the transcription start sites .

Other <dna>DNA elements</dna> present include a cluster of <dna>Myb sites</dna> , several <dna>Ets</dna> , an <dna>Ets related PU.1 site</dna> and an <dna>Sp1 site</dna> located within 600 bp of the <dna>transcription start sites</dna> .


In addition , DNA methylation was revealed as one of the possible factors in establishing MNDA expression .

In addition , DNA methylation was revealed as one of the possible factors in establishing <protein>MNDA</protein> expression .


The 5 ' flanking sequence has promoter activity which is elevated by interferon alpha .

The <dna>5 ' flanking sequence</dna> has promoter activity which is elevated by <protein>interferon alpha</protein> .


The findings indicate that MNDA expression is regulated by mechanisms similar to other myelomonocytic cell specific genes and genes up-regulated by interferon alpha .

The findings indicate that <protein>MNDA</protein> expression is regulated by mechanisms similar to other <dna>myelomonocytic cell specific genes</dna> and genes up-regulated by <protein>interferon alpha</protein> .


Abnormality of Oct-1 DNA binding in T cells from Sjogren 's syndrome patients .

Abnormality of <protein>Oct-1</protein> DNA binding in <cell_type>T cells</cell_type> from Sjogren 's syndrome patients .


Primary Sjogren 's syndrome ( SS ) is an autoimmune rheumatic disease characterized by T cell hypoactivity .


To understand the diminished T cell response to activation signals , we measured nucleoprotein DNA-binding activities regulating gene expression during T cell activation using the electrophoretic mobility shift assay .


Peripheral blood lymphocytes from 9/19 SS patients were found to be defective in their ability to bind an october sequence ( Oct-1 ) .

<cell_type>Peripheral blood lymphocytes</cell_type> from 9/19 SS patients were found to be defective in their ability to bind an <protein>october sequence</protein> ( <protein>Oct-1</protein> ) .


This Oct-1 -binding phenotype remained stable in culture for up to 3 days prior to activation .

This <protein>Oct-1</protein> -binding phenotype remained stable in culture for up to 3 days prior to activation .


This abnormality was not seen in resting T cells nor T cells from patients with systemic lupus erythematosus , rheumatoid arthritis ( RA ) , or SS accompanied by RA .

This abnormality was not seen in <cell_type>resting T cells</cell_type> nor <cell_type>T cells</cell_type> from patients with systemic lupus erythematosus , rheumatoid arthritis ( RA ) , or SS accompanied by RA .


The SS Oct-1 DNA-binding abnormality correlated significantly with an inability of cells to exit the Gzero/G1 cell cycle phase when stimulated in vitro .

The SS <protein>Oct-1</protein> DNA-binding abnormality correlated significantly with an inability of cells to exit the Gzero/G1 cell cycle phase when stimulated in vitro .


Importantly , nucleoprotein extracts showing decreased DNA-binding activity had normal amounts of Oct-1 proteins as determined by immunoprecipitation , implying a functional defect in the Oct-1 protein .

Importantly , nucleoprotein extracts showing decreased DNA-binding activity had normal amounts of <protein>Oct-1</protein> proteins as determined by immunoprecipitation , implying a functional defect in the <protein>Oct-1 protein</protein> .


Moreover , defective DNA binding was corrected by treatment with acid phosphatase .


Characterization of a new isoform of the NFAT ( nuclear factor of activated T cells ) gene family member NFATc [ published erratum appears in J Biol Chem 1996 Dec 27 ; 271 ( 52 ) : 33705 ]

Characterization of a new isoform of the <protein>NFAT</protein> ( <protein>nuclear factor of activated T cells</protein> ) gene family member <protein>NFATc</protein> [ published erratum appears in J Biol Chem 1996 Dec 27 ; 271 ( 52 ) : 33705 ]


The cyclosporin A ( CsA ) /FK506-sensitive nuclear factor of activated T cells ( NFAT ) plays a key role in the inducible expression of cytokine genes in T cells .

The <protein>cyclosporin A ( CsA ) /FK506-sensitive nuclear factor of activated T cells</protein> ( <protein>NFAT</protein> ) plays a key role in the inducible expression of <dna>cytokine genes</dna> in <cell_type>T cells</cell_type> .


Although NFAT has been recently shown to be inducible in several non-T immune cells , the NFAT gene family members characterized to date have been isolated only from T cells .

Although <protein>NFAT</protein> has been recently shown to be inducible in several <cell_type>non-T immune cells</cell_type> , the <dna>NFAT gene family members</dna> characterized to date have been isolated only from <cell_type>T cells</cell_type> .


To further characterize NFAT function in human B cells and to demonstrate cytokine gene specificity of NFAT proteins , we report here the isolation and characterization of a cDNA clone from the Raji B cell line .

To further characterize <protein>NFAT</protein> function in <cell_type>human B cells</cell_type> and to demonstrate cytokine gene specificity of <protein>NFAT proteins</protein> , we report here the isolation and characterization of a <dna>cDNA clone</dna> from the <cell_line>Raji B cell line</cell_line> .


The cDNA clone encodes a new isoform , NFATc.beta , of the NFAT gene family member NFATc ( designated here NFATc.alpha ) .

The <dna>cDNA clone</dna> encodes a new isoform , <protein>NFATc.beta</protein> , of the <protein>NFAT gene family member</protein> <protein>NFATc</protein> ( designated here <protein>NFATc.alpha</protein> ) .


The amino acid sequence of NFATc.beta differs from that of NFATc .

The <protein>amino acid sequence</protein> of <protein>NFATc.beta</protein> differs from that of <protein>NFATc</protein> .


alpha in the first NH2-terminal 29 residues and contains an additional region of 142 residues at the COOH terminus .

alpha in the first <protein>NH2-terminal 29 residues</protein> and contains an additional region of <protein>142 residues</protein> at the <protein>COOH terminus</protein> .


Northern analysis using a probe encompassing a common region of both isoforms showed two mRNA species of 2.7 and 4.5 kilobase pairs , while an NFATc.beta-specific probe detected only the 4.5-kilobase pair mRNA which was preferentially expressed in the spleen .

Northern analysis using a probe encompassing a common region of both isoforms showed two <rna>mRNA species</rna> of <rna>2.7 and 4.5 kilobase pairs</rna> , while an <dna>NFATc.beta-specific probe</dna> detected only the <rna>4.5-kilobase pair mRNA</rna> which was preferentially expressed in the spleen .


Transient expression of NFATc.beta was capable of activating an interleukin-2 NFAT-driven reporter gene in stimulated Jurkat cells in a CsA-sensitive manner .

Transient expression of <protein>NFATc.beta</protein> was capable of activating an <dna>interleukin-2 NFAT-driven reporter gene</dna> in <cell_line>stimulated Jurkat cells</cell_line> in a CsA-sensitive manner .


However , NFATc.beta neither bound to the kappa3 element ( an NFAT-binding site ) in the tumor necrosis factor-alpha promoter nor activated the tumor necrosis factor-alpha promoter in cotransfection assays .

However , <protein>NFATc.beta</protein> neither bound to the <dna>kappa3 element</dna> ( an <dna>NFAT-binding site</dna> ) in the <dna>tumor necrosis factor-alpha promoter</dna> nor activated the <dna>tumor necrosis factor-alpha promoter</dna> in cotransfection assays .


These data suggest that different members or isoforms of NFAT gene family may regulate inducible expression of different cytokine genes .

These data suggest that different members or isoforms of <dna>NFAT gene</dna> family may regulate inducible expression of different <dna>cytokine genes</dna> .


Regulation of interferon-gamma gene expression .

Regulation of <protein>interferon-gamma</protein> gene expression .


Interferon-gamma ( IFN-gamma ) , also known as type II interferon , is an important immunoregulatory gene that has multiple effects on the development , maturation , and function of the immune system .

Interferon-gamma ( <protein>IFN-gamma</protein> ) , also known as <protein>type II interferon</protein> , is an important immunoregulatory gene that has multiple effects on the development , maturation , and function of the immune system .


IFN-gamma mRNA and protein are expressed predominantly by T cells and large granular lymphocytes .

<rna>IFN-gamma mRNA</rna> and protein are expressed predominantly by <cell_type>T cells</cell_type> and <cell_type>large granular lymphocytes</cell_type> .


The IFN-gamma mRNA is induced/inhibited in these cell types by a wide variety of extracellular signals , thus implicating a number of diverse , yet convergent signal transduction pathways in its transcriptional control .

The <rna>IFN-gamma mRNA</rna> is induced/inhibited in these cell types by a wide variety of extracellular signals , thus implicating a number of diverse , yet convergent signal transduction pathways in its transcriptional control .


In this review , I describe how DNA methylation and specific DNA binding proteins may regulate transcription of the IFN-gamma gene in response to extracellular signals .

In this review , I describe how DNA methylation and specific <protein>DNA binding proteins</protein> may regulate transcription of the <dna>IFN-gamma gene</dna> in response to extracellular signals .


Transcriptional analysis of Epstein-Barr virus gene expression in EBV-positive gastric carcinoma : unique viral latency in the tumour cells .

Transcriptional analysis of Epstein-Barr virus gene expression in EBV-positive gastric carcinoma : unique viral latency in the <cell_type>tumour cells</cell_type> .


Although case-oriented evidence for an association of Epstein-Barr virus ( EBV ) with gastric carcinoma has been accumulating recently , the interaction ( s ) between EBV and gastric epithelial cells is/are largely unknown .

Although case-oriented evidence for an association of Epstein-Barr virus ( EBV ) with gastric carcinoma has been accumulating recently , the interaction ( s ) between EBV and <cell_type>gastric epithelial cells</cell_type> is/are largely unknown .


In this study , we examined seven EBV-positive gastric carcinoma tissues for viral gene expression at the mRNA level , from which studies on the EBV oncogenicity in human epithelial cells will benefit .

In this study , we examined seven EBV-positive gastric carcinoma tissues for viral gene expression at the mRNA level , from which studies on the EBV oncogenicity in <cell_type>human epithelial cells</cell_type> will benefit .


Reverse transcription-PCR analysis showed that all seven EBV-positive tumour tissues constitutively expressed EBV nuclear antigen ( EBNA ) 1 mRNA , but not EBNA2 mRNA .

Reverse transcription-PCR analysis showed that all seven EBV-positive tumour tissues constitutively expressed <rna>EBV nuclear antigen ( EBNA ) 1 mRNA</rna> , but not <rna>EBNA2 mRNA</rna> .


The EBNA transcription was initiated from one of three EBNA promoters , Qp : by contrast , both Cp and Wp were silent , thus resulting in the lack of EBNA2 mRNA .

The <protein>EBNA</protein> transcription was initiated from one of three <dna>EBNA promoters</dna> , <dna>Qp</dna> : by contrast , both <dna>Cp</dna> and <dna>Wp</dna> were silent , thus resulting in the lack of <rna>EBNA2 mRNA</rna> .


Latent membrane protein ( LMP ) 2A mRNA was detected in three of seven cases ; however , neither LMP1 nor LMP2B mRNA was detected in any of the tumours tested .

<rna>Latent membrane protein ( LMP ) 2A mRNA</rna> was detected in three of seven cases ; however , <rna>neither LMP1 nor LMP2B mRNA</rna> was detected in any of the tumours tested .


Transcripts from the BamHI-A region of the viral genome were detectable in all cases .

Transcripts from the <dna>BamHI-A region</dna> of the <dna>viral genome</dna> were detectable in all cases .


BZLF1 mRNA and the product , an immediate-early gene for EBV replication , was not expressed in any of them , thereby suggesting that the tumour cells carried EBV genomes in a tightly latent form .

<rna>BZLF1 mRNA</rna> and the product , an <dna>immediate-early gene</dna> for EBV replication , was not expressed in any of them , thereby suggesting that the <cell_type>tumour cells</cell_type> carried <dna>EBV genomes</dna> in a tightly latent form .


These findings further extended our previous data regarding EBV latency in gastric carcinoma cells at the protein level , and have affirmed that the programme of viral gene expression in the tumour more closely resembles 'latency I ' represented by Burkitt 's lymphoma than 'latency II ' represented by the majority of nasopharyngeal carcinomas .

These findings further extended our previous data regarding EBV latency in <cell_type>gastric carcinoma cells</cell_type> at the protein level , and have affirmed that the programme of viral gene expression in the tumour more closely resembles 'latency I ' represented by Burkitt 's lymphoma than 'latency II ' represented by the majority of nasopharyngeal carcinomas .


Characterization of Grb2-binding proteins in human platelets activated by Fc gamma RIIA cross-linking .

Characterization of <protein>Grb2-binding proteins</protein> in <cell_type>human platelets</cell_type> activated by <protein>Fc gamma RIIA</protein> cross-linking .


Glutathione-S-transferase ( GST ) -Grb2 fusion proteins have been used to identify the potential role of Grb2-binding proteins in platelet activation by the platelet low-affinity IgG receptor , Fc gamma RIIA .

<protein>Glutathione-S-transferase ( GST ) -Grb2 fusion proteins</protein> have been used to identify the potential role of <protein>Grb2-binding proteins</protein> in <cell_type>platelet</cell_type> activation by the <protein>platelet low-affinity IgG receptor</protein> , <protein>Fc gamma RIIA</protein> .


Two tyrosine phosphoproteins of 38 and 63 kD bind to the SH2 domain of Grb2 following Fc gamma RIIA stimulation of platelets .

Two <protein>tyrosine phosphoproteins</protein> of 38 and 63 kD bind to the <protein>SH2 domain</protein> of <protein>Grb2</protein> following <protein>Fc gamma RIIA</protein> stimulation of <cell_type>platelets</cell_type> .


Both are located in the particulate fraction following platelet activation and are also able to bind to a GST-construct containing the SH2 and SH3 domains of phospholipase C gamma 1 .

Both are located in the particulate fraction following <cell_type>platelet</cell_type> activation and are also able to bind to a <protein>GST-construct</protein> containing the <protein>SH2 and SH3 domains</protein> of <protein>phospholipase C gamma 1</protein> .


p38 also forms a complex with the tyrosine kinase csk in stimulated cells and is a substrate for the kinase .

p38 also forms a complex with the <protein>tyrosine kinase csk</protein> in <cell_type>stimulated cells</cell_type> and is a substrate for the <protein>kinase</protein> .


The SH3 domains of Grb2 form a stable complex with SOS1 and two proteins of 75 kD and 120 kD , which undergo tyrosine phosphorylation in Fc gamma RIIA stimulated cells .

The <protein>SH3 domains</protein> of <protein>Grb2</protein> form a stable complex with <protein>SOS1</protein> and two proteins of <protein>75 kD</protein> and <protein>120 kD</protein> , which undergo tyrosine phosphorylation in <cell_line>Fc gamma RIIA stimulated cells</cell_line> .


The 75-kD protein is recognized by antibodies to SLP-76 , which has recently been isolated from T cells and sequenced .

The <protein>75-kD protein</protein> is recognized by antibodies to <protein>SLP-76</protein> , which has recently been isolated from <cell_type>T cells</cell_type> and sequenced .


Tyrosine phosphorylation of p38 and p63 is also observed in platelets stimulated by the tyrosine kinase -linked receptor agonist collagen and by the G protein -coupled receptor agonist thrombin , although phosphorylation of SLP-76 is only observed in collagen -stimulated platelets .

Tyrosine phosphorylation of <protein>p38</protein> and <protein>p63</protein> is also observed in <cell_type>platelets</cell_type> stimulated by the <protein>tyrosine kinase</protein> -linked receptor agonist <protein>collagen</protein> and by the <protein>G protein</protein> -coupled receptor agonist <protein>thrombin</protein> , although phosphorylation of <protein>SLP-76</protein> is only observed in <protein>collagen</protein> -stimulated <cell_type>platelets</cell_type> .


p38 and p63 may provide a docking site for Grb2 , thereby linking Grb2 SH3-binding proteins SOS1 , SLP-76 , and p120 to downstream signalling events .

<protein>p38</protein> and <protein>p63</protein> may provide a docking site for <protein>Grb2</protein> , thereby linking <protein>Grb2 SH3-binding proteins</protein> <protein>SOS1</protein> , <protein>SLP-76</protein> , and <protein>p120</protein> to downstream signalling events .


Constitutive expression of specific interferon isotypes in peripheral blood leukocytes from normal individuals and in promonocytic U937 cells .

Constitutive expression of specific <protein>interferon isotypes</protein> in <cell_type>peripheral blood leukocytes</cell_type> from normal individuals and in <cell_line>promonocytic U937 cells</cell_line> .


Constitutive expression of IFN-alpha5 and IFN-beta was detected in different lymphoid cells including peripheral blood mononuclear cells from normal individuals following amplification of IFN mRNA by reverse transcriptase -polymerase chain reaction and direct sequencing of the amplified product .

Constitutive expression of <protein>IFN-alpha5</protein> and <protein>IFN-beta</protein> was detected in different <cell_type>lymphoid cells</cell_type> including <cell_type>peripheral blood mononuclear cells</cell_type> from normal individuals following amplification of <rna>IFN mRNA</rna> by <protein>reverse transcriptase</protein> -polymerase chain reaction and direct sequencing of the <dna>amplified product</dna> .


The activated form of the interferon-induced transcription factor complex ISGF3 was also detected in nuclear extracts from uninduced cells .

The activated form of the <protein>interferon-induced transcription factor complex</protein> <protein>ISGF3</protein> was also detected in nuclear extracts from <cell_line>uninduced cells</cell_line> .


Culture supernatants from uninduced U937 cells were also found to activate an ISRE cloned upstream of the luciferase reporter gene , indicating the presence of endogenous IFN activity equivalent to approximately 0.3 to 0.5 IU/mL .

Culture supernatants from <cell_line>uninduced U937 cells</cell_line> were also found to activate an <dna>ISRE</dna> cloned upstream of the <dna>luciferase reporter gene</dna> , indicating the presence of <protein>endogenous IFN</protein> activity equivalent to approximately 0.3 to 0.5 IU/mL .


This endogenous IFN was also shown to play a role in maintaining the basal level of expression of the major histocompatibility class I genes in lymphoid cells .

This <protein>endogenous IFN</protein> was also shown to play a role in maintaining the basal level of expression of the <dna>major histocompatibility class I genes</dna> in <cell_type>lymphoid cells</cell_type> .


These results suggest that IFN-alpha5 and IFN-beta are produced at low levels in normal tissues and play an important role in the regulation of cell function and in the maintenance of homeostasis .

These results suggest that <protein>IFN-alpha5</protein> and <protein>IFN-beta</protein> are produced at low levels in normal tissues and play an important role in the regulation of cell function and in the maintenance of homeostasis .


An IL-2 response element in the human IL-2 receptor alpha chain promoter is a composite element that binds Stat5 , Elf-1 , HMG-I ( Y ) and a GATA family protein .

An <dna>IL-2 response element</dna> in the <dna>human IL-2 receptor alpha chain promoter</dna> is a <dna>composite element</dna> that binds <protein>Stat5</protein> , <protein>Elf-1</protein> , <protein>HMG-I ( Y )</protein> and a <protein>GATA family protein</protein> .


Expression of the human interleukin-2 ( IL-2 ) receptor alpha chain gene is potently upregulated by its own ligand , IL-2 .

Expression of the <dna>human interleukin-2 ( IL-2 ) receptor alpha chain gene</dna> is potently upregulated by its own ligand , <protein>IL-2</protein> .


In this study , we characterize an essential upstream IL-2 response element that contains both consensus and non-consensus GAS motifs , two putative Ets binding sites ( EBS ) , one of which overlaps the consensus GAS motif , and a GATA motif , which overlaps the non-consensus GAS motif .

In this study , we characterize an essential upstream <dna>IL-2 response element</dna> that contains both <dna>consensus and non-consensus GAS motifs</dna> , two putative <dna>Ets binding sites</dna> ( <dna>EBS</dna> ) , one of which overlaps the <dna>consensus GAS motif</dna> , and a <dna>GATA motif</dna> , which overlaps the <dna>non-consensus GAS motif</dna> .


We demonstrate that although the individual components of this element do not respond to IL-2 , together they form a composite element capable of conferring IL-2 responsiveness to a heterologous promoter .

We demonstrate that although the individual components of this element do not respond to <protein>IL-2</protein> , together they form a composite element capable of conferring <protein>IL-2</protein> responsiveness to a <dna>heterologous promoter</dna> .


Multiple factors including Stat5 , Elf-1 , HMG-I ( Y ) and GATA family proteins bind to the IL-2 response element and mutation of any one of these binding sites diminishes the activity of this element .

Multiple factors including <protein>Stat5</protein> , <protein>Elf-1</protein> , <protein>HMG-I ( Y )</protein> and <protein>GATA family proteins</protein> bind to the <dna>IL-2 response element</dna> and mutation of any one of these binding sites diminishes the activity of this element .


An unidentified Ets family protein binds to the EBS overlapping the consensus GAS motif and appears to negatively regulate the human IL-2R alpha promoter .

An unidentified <protein>Ets family protein</protein> binds to the <dna>EBS</dna> overlapping the <dna>consensus GAS motif</dna> and appears to negatively regulate the <dna>human IL-2R alpha promoter</dna> .


Thus , IL-2 -induced IL-2R alpha promoter activity requires a complex upstream element , which appears to contain binding sites for both positive and negative regulatory factors .

Thus , <protein>IL-2</protein> -induced <dna>IL-2R alpha promoter</dna> activity requires a <dna>complex upstream element</dna> , which appears to contain <dna>binding sites</dna> for both <protein>positive and negative regulatory factors</protein> .


Lymphocytes from CML patients lack a 47 kDa factor having affinity for a genomic sterol regulatory sequence .

<cell_type>Lymphocytes</cell_type> from CML patients lack a <protein>47 kDa factor</protein> having affinity for a <dna>genomic sterol regulatory sequence</dna> .


Deranged cellular cholesterol homeostasis has been widely recognized in the initiation as well as progression of various types of cancers including chronic myeloid leukaemia ( CML ) .


Since the human genomic sterol regulatory element ( SRE ) has been shown to regulate various key genes involved in this phenomenon , the present study revealed the existence of a unique 47 kDa protein factor having affinity for this SRE sequence in lymphocytes from normal subjects , as well as its absence in lymphocytes from untreated CML patients .

Since the <dna>human genomic sterol regulatory element</dna> ( <dna>SRE</dna> ) has been shown to regulate various key genes involved in this phenomenon , the present study revealed the existence of a unique <protein>47 kDa protein factor</protein> having affinity for this <dna>SRE sequence</dna> in <cell_type>lymphocytes</cell_type> from normal subjects , as well as its absence in <cell_type>lymphocytes</cell_type> from untreated CML patients .


However , this factor appeared when these CML patients achieved complete haematological remission ( CHR ) through alpha-interferon therapy .

However , this factor appeared when these CML patients achieved complete haematological remission ( CHR ) through <protein>alpha-interferon</protein> therapy .


Furthermore , an inverse relationship was also observed between the LDL receptor gene expression at the transcriptional level and the binding affinity of this 47 kDa protein factor to the SRE sequence .

Furthermore , an inverse relationship was also observed between the <dna>LDL receptor gene</dna> expression at the transcriptional level and the binding affinity of this <protein>47 kDa protein factor</protein> to the <dna>SRE sequence</dna> .


Based upon these results we propose that this factor may have a role in pathophysiology of chronic myeloid leukaemia .


Cloning and characterization of the beta subunit of human proximal sequence element-binding transcription factor and its involvement in transcription of small nuclear RNA genes by RNA polymerases II and III .

Cloning and characterization of the <protein>beta subunit</protein> of <protein>human proximal sequence element-binding transcription factor</protein> and its involvement in transcription of <dna>small nuclear RNA genes</dna> by <protein>RNA polymerases II and III</protein> .


The proximal sequence element ( PSE ) -binding transcription factor ( PTF ) , which binds the PSE of both RNA polymerase II -and RNA polymerase III-transcribed mammalian small nuclear RNA ( snRNA ) genes , is essential for their transcription .

The <protein>proximal sequence element ( PSE ) -binding transcription factor</protein> ( <protein>PTF</protein> ) , which binds the <dna>PSE</dna> of both <dna>RNA polymerase II -and RNA polymerase III-transcribed mammalian small nuclear RNA ( snRNA ) genes</dna> , is essential for their transcription .


We previously reported the purification of human PTF , a complex of four subunits , and the molecular cloning and characterization of PTF gamma and delta subunits .

We previously reported the purification of <protein>human PTF</protein> , a complex of <protein>four subunits</protein> , and the molecular cloning and characterization of <protein>PTF gamma and delta subunits</protein> .


Here we describe the isolation and expression of a cDNA encoding PTF beta , as well as functional studies using anti-PTF beta antibodies .

Here we describe the isolation and expression of a <dna>cDNA</dna> encoding <protein>PTF beta</protein> , as well as functional studies using <protein>anti-PTF beta antibodies</protein> .


Native PTF beta , in either protein fractions or a PTF-Oct-1-DNA complex , can be recognized by polyclonal antibodies raised against recombinant PTF beta .

Native <protein>PTF beta</protein> , in either protein fractions or a <protein>PTF-Oct-1-DNA complex</protein> , can be recognized by <protein>polyclonal antibodies</protein> raised against <protein>recombinant PTF beta</protein> .


Immunodepletion studies show that PTF beta is required for transcription of both classes of snRNA genes in vitro .

Immunodepletion studies show that <protein>PTF beta</protein> is required for transcription of both classes of <dna>snRNA genes</dna> in vitro .


In addition , immunoprecipitation analyses demonstrate that substantial and similar molar amounts of TATA-binding protein ( TBP ) and TFIIIB90 can weakly associate with PTF at low salt conditions , but this association is dramatically reduced at high salt concentrations .

In addition , immunoprecipitation analyses demonstrate that substantial and similar molar amounts of <protein>TATA-binding protein</protein> ( <protein>TBP</protein> ) and <protein>TFIIIB90</protein> can weakly associate with <protein>PTF</protein> at low salt conditions , but this association is dramatically reduced at high salt concentrations .


Along with our previous demonstration of both physical interactions between PTF gamma/PTF delta and TBP and the involvement of TFIIIB90 in the transcription of class III snRNA genes , these results are consistent with the notion that a TBP-containing complex related to TFIIIB is required for the transcription of class III snRNA genes , and acts through weak interaction with the four-subunit PTF .

Along with our previous demonstration of both physical interactions between <protein>PTF gamma/PTF delta</protein> and <protein>TBP</protein> and the involvement of <protein>TFIIIB90</protein> in the transcription of <dna>class III snRNA genes</dna> , these results are consistent with the notion that a <protein>TBP-containing complex</protein> related to <protein>TFIIIB</protein> is required for the transcription of <dna>class III snRNA genes</dna> , and acts through weak interaction with the <protein>four-subunit PTF</protein> .


Attenuated function of a variant form of the helix-loop-helix protein , Id-3 , generated by an alternative splicing mechanism .

Attenuated function of a variant form of the <protein>helix-loop-helix protein</protein> , <protein>Id-3</protein> , generated by an alternative splicing mechanism .


The Id family of helix-loop-helix proteins function as negative regulators of DNA binding , basic helix-loop-helix proteins in the regulation of cell growth and differentiation .

The Id family of <protein>helix-loop-helix proteins</protein> function as negative regulators of DNA binding , basic <protein>helix-loop-helix proteins</protein> in the regulation of cell growth and differentiation .


We report here on the identification of a 17 kDa variant of the 14 kDa Id-3 protein termed Id-3L ( long version ) which possesses a unique 60 amino acid carboxy-terminus generated by read through of a ' coding intron ' and alternative splicing .

We report here on the identification of a <protein>17 kDa variant</protein> of the <protein>14 kDa Id-3</protein> protein termed <protein>Id-3L</protein> ( long version ) which possesses a unique <protein>60 amino acid carboxy-terminus</protein> generated by read through of a ' <dna>coding intron</dna> ' and alternative splicing .


Northern analysis revealed expression of a minor 1.1 kb Id-3L transcript together with the predominant 0.95 kb Id-3 transcript in the majority of adult human tissues analysed .

Northern analysis revealed expression of a minor <rna>1.1 kb Id-3L transcript</rna> together with the predominant <rna>0.95 kb Id-3 transcript</rna> in the majority of adult human tissues analysed .


The variant Id-3L protein is functionally distinguishable from conventional Id-3 since in in vitro DNA mobility shift assays , it was greatly impaired in its ability to abrogate binding of the basic helix-loop-helix protein , E47 , to an E box recognition sequence .

The variant <protein>Id-3L protein</protein> is functionally distinguishable from conventional <protein>Id-3</protein> since in in vitro DNA mobility shift assays , it was greatly impaired in its ability to abrogate binding of the basic <protein>helix-loop-helix protein</protein> , <protein>E47</protein> , to an <dna>E box recognition sequence</dna> .


Tyloxapol inhibits NF-kappa B and cytokine release , scavenges HOCI , and reduces viscosity of cystic fibrosis sputum .

Tyloxapol inhibits <protein>NF-kappa B</protein> and <protein>cytokine</protein> release , scavenges <protein>HOCI</protein> , and reduces viscosity of cystic fibrosis sputum .


Cystic fibrosis ( CF ) patients develop progressive cytokine -mediated inflammatory lung disease , with abundant production of thick , tenacious , protease -and oxidant-rich purulent airway secretions that are difficult to clear even with physiotherapy .

Cystic fibrosis ( CF ) patients develop progressive <protein>cytokine</protein> -mediated inflammatory lung disease , with abundant production of thick , tenacious , <protein>protease</protein> -and oxidant-rich purulent airway secretions that are difficult to clear even with physiotherapy .


In the search for a potential treatment , we have tested tyloxapol , an alkylaryl polyether alcohol polymer detergent previously used as a mucolytic agent in adult chronic bronchitis .


Tyloxapol inhibits activation of the transcription factor nuclear factor-kappa B ( NK-kappa B ) , reduces resting secretion of the cytokine interleukin-8 ( IL-8 ) in cultured human monocytes , and inhibits lipopolysaccharide ( LPS ) -stimulated release of tumor necrosis factor-alpha ( TNF-alpha ) , IL-1 beta , IL-6 , IL-8 , granulocyte-macrophage colony-stimulating factor ( GM-CSF ) , and the eiconsanoids thromboxane A2 and leukotriene B4 ( LTB4 ) .

Tyloxapol inhibits activation of the <protein>transcription factor nuclear factor-kappa B</protein> ( <protein>NK-kappa B</protein> ) , reduces resting secretion of the <protein>cytokine</protein> <protein>interleukin-8</protein> ( <protein>IL-8</protein> ) in <cell_line>cultured human monocytes</cell_line> , and inhibits lipopolysaccharide ( LPS ) -stimulated release of <protein>tumor necrosis factor-alpha</protein> ( <protein>TNF-alpha</protein> ) , <protein>IL-1 beta</protein> , <protein>IL-6</protein> , <protein>IL-8</protein> , <protein>granulocyte-macrophage colony-stimulating factor</protein> ( <protein>GM-CSF</protein> ) , and the eiconsanoids thromboxane A2 and leukotriene B4 ( LTB4 ) .


We have previously shown that tyloxapol is a potent antioxidant for hydroxyl radicals ( OH ) .


Tyloxapol ( 0.05 to 0.1 % wt/vol ) effectively scavenges the oxidant hypochlorous acid ( HOCl ; 1 to 7.5 mM ) in vitro , and protects from HOCl-mediated lung injury in rats .


Tyloxapol also reduces the viscosity of CF sputum ( from 463 +/- 133 to 128 +/- 52 centipoise ) .


We conclude that tyloxapol is potentially useful as a new antiinflammatory therapy for CF lung disease , and could possibly promote clearance of secretions in the CF airway .


Elevated cyclic AMP inhibits NF-kappaB -mediated transcription in human monocytic cells and endothelial cells .

Elevated cyclic AMP inhibits <protein>NF-kappaB</protein> -mediated transcription in human monocytic cells and endothelial cells .


The NF-kappaB/Rel family of transcription factors regulates the inducible expression of many genes in activated human monocytes and endothelial cells .

The <protein>NF-kappaB/Rel family</protein> of <protein>transcription factors</protein> regulates the inducible expression of many genes in <cell_type>activated human monocytes</cell_type> and <cell_type>endothelial cells</cell_type> .


In this study , we examined the molecular mechanism by which agents that elevate intracellular cAMP inhibit the expression of the tumor necrosis factor alpha ( TNFalpha ) , tissue factor , endothelial leukocyte adhesion molecule-1 , and vascular cell adhesion molecule-1 genes .

In this study , we examined the molecular mechanism by which agents that elevate intracellular cAMP inhibit the expression of the <protein>tumor necrosis factor alpha</protein> ( <protein>TNFalpha</protein> ) , <protein>tissue factor</protein> , <protein>endothelial leukocyte adhesion molecule-1</protein> , and <dna>vascular cell adhesion molecule-1 genes</dna> .


Both forskolin and dibutyryl cAMP , which elevate intracellular cAMP by independent mechanisms , inhibited TNFalpha and tissue factor expression at the level of transcription .

Both forskolin and dibutyryl cAMP , which elevate intracellular cAMP by independent mechanisms , inhibited <protein>TNFalpha</protein> and <protein>tissue factor</protein> expression at the level of transcription .


Induction of NF-kappaB -dependent gene expression in transiently transfected human monocytic THP-1 cells and human umbilical vein endothelial cells was inhibited by elevated cAMP and by overexpression of the catalytic subunit of protein kinase A ( PKA ) .

Induction of <protein>NF-kappaB</protein> -dependent gene expression in transiently transfected <cell_line>human monocytic THP-1 cells</cell_line> and <cell_type>human umbilical vein endothelial cells</cell_type> was inhibited by elevated cAMP and by overexpression of the <protein>catalytic subunit</protein> of <protein>protein kinase A</protein> ( <protein>PKA</protein> ) .


Elevated cAMP did not prevent nuclear translocation of p50/p65 and c-Rel/p65 heterodimers , decrease nuclear translocation of p65 , or significantly modify TNFalpha -induced phosphorylation of p65 .

Elevated cAMP did not prevent nuclear translocation of <protein>p50/p65</protein> and <protein>c-Rel/p65 heterodimers</protein> , decrease nuclear translocation of <protein>p65</protein> , or significantly modify <protein>TNFalpha</protein> -induced phosphorylation of <protein>p65</protein> .


Functional studies demonstrated that transcriptional activation of a plasmid containing multimerized kappaB sites by p65 was inhibited by agents that elevate cAMP and by overexpression of the catalytic subunit of PKA .

Functional studies demonstrated that transcriptional activation of a <dna>plasmid</dna> containing <dna>multimerized kappaB sites</dna> by <protein>p65</protein> was inhibited by agents that elevate cAMP and by overexpression of the <protein>catalytic subunit</protein> of <protein>PKA</protein> .


This study indicates that activation of PKA reduces the induction of a distinct set of genes in monocytes and endothelial cells by inhibiting NF-kappaB -mediated transcription .

This study indicates that activation of <protein>PKA</protein> reduces the induction of a distinct set of <dna>genes</dna> in <cell_type>monocytes</cell_type> and <cell_type>endothelial cells</cell_type> by inhibiting <protein>NF-kappaB</protein> -mediated transcription .


Molecular mechanisms of steroid action : a novel type of cross-talk between glucocorticoids and NF-kappa B transcription factors .

Molecular mechanisms of steroid action : a novel type of cross-talk between glucocorticoids and <protein>NF-kappa B</protein> <protein>transcription factors</protein> .


Despite the widespread use of glucocorticoids in the treatment of diseases characterized by inflammation , the molecular mechanism ( s ) by which these hormones exert this beneficial effect in patients with asthma remains to be elucidated .


Therefore , we have studied the transcriptional regulation of intercellular adhesion molecule-1 ( ICAM-1 ) as adhesion molecules are likely to play a causal role in inflammation in promoting cell-cell and cell-matrix interactions .

Therefore , we have studied the transcriptional regulation of <protein>intercellular adhesion molecule-1</protein> ( <protein>ICAM-1</protein> ) as <protein>adhesion molecules</protein> are likely to play a causal role in inflammation in promoting cell-cell and cell-matrix interactions .


We observed that in a monocytic ( U937 ) and a bronchial epithelial ( H292 ) cell-line dexamethasone strongly suppressed basal and induced ICAM-1 expression .

We observed that in a <cell_line>monocytic ( U937 )</cell_line> and a <cell_line>bronchial epithelial ( H292 ) cell-line</cell_line> dexamethasone strongly suppressed basal and induced <protein>ICAM-1</protein> expression .


Subsequent analysis of the human ICAM-1 promoter has revealed that both 12-O-tetradecanoylphorbol 13-acetate ( TPA ) and tumour necrosis factor-alpha ( TNF-alpha ) upregulate ICAM-1 expression through the presence of a nuclear factor ( NF-kappa B ) target sequence ( TGGAAATTCC ) .

Subsequent analysis of the <dna>human ICAM-1 promoter</dna> has revealed that both 12-O-tetradecanoylphorbol 13-acetate ( TPA ) and <protein>tumour necrosis factor-alpha</protein> ( <protein>TNF-alpha</protein> ) upregulate <protein>ICAM-1</protein> expression through the presence of a <dna>nuclear factor ( NF-kappa B ) target sequence</dna> ( TGGAAATTCC ) .


No glucocorticoid recognition sequences are present in this promoter region and dexamethasone is still able to repress transcription when the multimerized NF-kappa B sequence is transactivated by TNF-alpha upon transfection in 293 cells .

No <dna>glucocorticoid recognition sequences</dna> are present in this <dna>promoter region</dna> and dexamethasone is still able to repress transcription when the <dna>multimerized NF-kappa B sequence</dna> is transactivated by <protein>TNF-alpha</protein> upon transfection in <cell_line>293 cells</cell_line> .


We propose that direct interaction between the glucocorticoid receptor and nuclear factor-kappa B factors is at least a partial explanation for the effects of this hormone in inflammatory diseases .

We propose that direct interaction between the <protein>glucocorticoid receptor</protein> and <protein>nuclear factor-kappa B factors</protein> is at least a partial explanation for the effects of this hormone in inflammatory diseases .


Abnormalities of p16 , p15 and CDK4 genes in recurrent malignant astrocytomas .

Abnormalities of <dna>p16 , p15 and CDK4 genes</dna> in recurrent malignant astrocytomas .


Abnormalities in the p16 , p15 and CDK4 genes that regulate transition through the G1 phase of the cell cycle have been implicated in the malignant progression of astrocytomas .

Abnormalities in the <dna>p16 , p15 and CDK4 genes</dna> that regulate transition through the G1 phase of the cell cycle have been implicated in the malignant progression of astrocytomas .


The results of the present study demonstrate that dysfunction of these genes also occurs during recurrence of glial tumors that were highly malignant at first presentation .

The results of the present study demonstrate that dysfunction of these <dna>genes</dna> also occurs during recurrence of glial tumors that were highly malignant at first presentation .


Analysis of 10 matched pairs of high grade malignant astrocytomas and their subsequent recurrences identified three distinct groups .


The primary and recurrent tumors in Group A did not show structural alterations in the p16 , p15 or CDK4 genes , whereas homozygous codeletion of p16 and p15 was observed in both primary and recurrent tumors in Group B .

The primary and recurrent tumors in Group A did not show structural alterations in the <dna>p16 , p15 or CDK4 genes</dna> , whereas homozygous codeletion of <dna>p16</dna> and <dna>p15</dna> was observed in both primary and recurrent tumors in Group B .


The primary tumors in Group C had a normal profile of p16 , p15 and CDK4 at presentation .

The primary tumors in Group C had a normal profile of <protein>p16</protein> , <protein>p15</protein> and <protein>CDK4</protein> at presentation .


Upon recurrence , however , the tumors sustained either deletion of p16 alone or codeletion of both p16 and p15 or amplification of CDK4 .

Upon recurrence , however , the tumors sustained either deletion of <protein>p16</protein> alone or codeletion of both <protein>p16</protein> and <protein>p15</protein> or amplification of <protein>CDK4</protein> .


Analysis of the molecular differences between primary anaplastic astrocytomas/glioblastomas and their subsequent recurrences , which are clinically indistinguishable , may provide better therapeutic options for treatment .


BCL-6 , a POZ/zinc-finger protein , is a sequence-specific transcriptional repressor .

<protein>BCL-6</protein> , a <protein>POZ/zinc-finger protein</protein> , is a <protein>sequence-specific transcriptional repressor</protein> .


Approximately 40 % of diffuse large cell lymphoma are associated with chromosomal translocations that deregulate the expression of the BCL6 gene by juxtaposing heterologous promoters to the BCL-6 coding domain .

Approximately 40 % of diffuse large cell lymphoma are associated with chromosomal translocations that deregulate the expression of the <dna>BCL6 gene</dna> by juxtaposing <dna>heterologous promoters</dna> to the <dna>BCL-6 coding domain</dna> .


The BCL6 gene encodes a 95-kDa protein containing six C-terminal zinc-finger motifs and an N-terminal POZ domain , suggesting that it may function as a transcription factor .

The <dna>BCL6 gene</dna> encodes a <protein>95-kDa protein</protein> containing six <protein>C-terminal zinc-finger motifs</protein> and an <protein>N-terminal POZ domain</protein> , suggesting that it may function as a <protein>transcription factor</protein> .


By using a DNA sequence selected for its ability to bind recombinant BCL-6 in vitro , we show here that BCL-6 is present in DNA-binding complexes in nuclear extracts from various B-cell lines .

By using a <dna>DNA sequence</dna> selected for its ability to bind <protein>recombinant BCL-6</protein> in vitro , we show here that <protein>BCL-6</protein> is present in <protein>DNA-binding complexes</protein> in nuclear extracts from various <cell_line>B-cell lines</cell_line> .


In transient transfectin experiments , BCL6 can repress transcription from promoters linked to its DNA target sequence and this activity is dependent upon specific DNA-binding and the presence of an intact N-terminal half of the protein .

In transient transfectin experiments , <protein>BCL6</protein> can repress transcription from <dna>promoters</dna> linked to its <dna>DNA target sequence</dna> and this activity is dependent upon specific DNA-binding and the presence of an intact <protein>N-terminal half</protein> of the protein .


We demonstrate that this part of the BCL6 molecule contains an autonomous transrepressor domain and that two noncontiguous regions , including the POZ motif , mediate maximum transrepressive activity .

We demonstrate that this part of the <protein>BCL6 molecule</protein> contains an <protein>autonomous transrepressor domain</protein> and that two <protein>noncontiguous regions</protein> , including the <protein>POZ motif</protein> , mediate maximum transrepressive activity .


These results indicate that the BCL-6 protein can function as a sequence-specific transcriptional repressor and have implications for the role of BCL6 in normal lymphoid development and lymphomagenesis .

These results indicate that the <protein>BCL-6 protein</protein> can function as a <protein>sequence-specific transcriptional repressor</protein> and have implications for the role of <protein>BCL6</protein> in normal lymphoid development and lymphomagenesis .


Signals leading to the activation of NF-kappa B transcription factor are stronger in neonatal than adult T lymphocytes .

Signals leading to the activation of <protein>NF-kappa B transcription factor</protein> are stronger in <cell_type>neonatal than adult T lymphocytes</cell_type> .


The molecular background of the defects in the immune reactivity of human neonates has not been fully elucidated .


As the NF-kappa B transcription factor has a central role in the control of transcription of several genes involved in immune and inflammatory responses , the authors have analysed the activation of NF-kappa B in human umbilical cord T lymphocytes .

As the <protein>NF-kappa B transcription factor</protein> has a central role in the control of transcription of several <dna>genes</dna> involved in immune and inflammatory responses , the authors have analysed the activation of <protein>NF-kappa B</protein> in <cell_type>human umbilical cord T lymphocytes</cell_type> .


The activity was tested by quantitating the nuclear proteins binding to an oligonucleotide containing the consensus kappa B binding sequence ( electrophoretic mobility shift assay ) .

The activity was tested by quantitating the <protein>nuclear proteins</protein> binding to an oligonucleotide containing the <dna>consensus kappa B binding sequence</dna> ( electrophoretic mobility shift assay ) .


The data obtained demonstrate that phorbol dibutyrate/calcium ionophore A23187 ( PDBu/iono ) combination induced a clearly higher nuclear translocation of NF-kappa B in neonatal than adult T cells .

The data obtained demonstrate that phorbol dibutyrate/calcium ionophore A23187 ( PDBu/iono ) combination induced a clearly higher nuclear translocation of <protein>NF-kappa B</protein> in <cell_type>neonatal than adult T cells</cell_type> .


This higher NF-kappa B activity was restricted to the CD4+ T-cell subset .

This higher <protein>NF-kappa B</protein> activity was restricted to the <cell_type>CD4+ T-cell subset</cell_type> .


Analysis of the nuclear extracts with antibodies directed against the major components of NF-kappa B the p50 and RelA ( p65 ) proteins , indicated that the composition of NF-kappa B was similar in neonatal and adult cells .

Analysis of the nuclear extracts with <protein>antibodies</protein> directed against the major components of <protein>NF-kappa B</protein> the <protein>p50 and RelA ( p65 ) proteins</protein> , indicated that the composition of <protein>NF-kappa B</protein> was similar in <cell_type>neonatal and adult cells</cell_type> .


These results suggest that neonatal T cells are exposed to oxidative stress-inducing signals during delivery and/or are inherently more sensitive to NF-kappa B activating signals than adult T cells .

These results suggest that <cell_type>neonatal T cells</cell_type> are exposed to oxidative stress-inducing signals during delivery and/or are inherently more sensitive to <protein>NF-kappa B</protein> activating signals than <cell_type>adult T cells</cell_type> .


Dual action of retinoic acid on human embryonic/fetal hematopoiesis : blockade of primitive progenitor proliferation and shift from multipotent/erythroid/monocytic to granulocytic differentiation program .


In preliminary studies , we have analyzed the hematopoietic growth factor ( HGF ) requirement of hematopoietic progenitor cells ( HPCs ) purified from embryonic-fetal liver ( FL ) and grown in fetal calf serum-supplemented ( FCS+ ) clonogenic culture .

In preliminary studies , we have analyzed the <protein>hematopoietic growth factor</protein> ( <protein>HGF</protein> ) requirement of <cell_type>hematopoietic progenitor cells</cell_type> ( <cell_type>HPCs</cell_type> ) purified from embryonic-fetal liver ( FL ) and grown in fetal calf serum-supplemented ( FCS+ ) clonogenic culture .


The key role of erythropoietin ( Epo ) for colony formation by early erythroid progenitors ( burst-forming units-erythroid [ BFU-E ] ) has been confirmed .

The key role of <protein>erythropoietin</protein> ( <protein>Epo</protein> ) for colony formation by <cell_type>early erythroid progenitors</cell_type> ( <cell_type>burst-forming units-erythroid</cell_type> [ <cell_type>BFU-E</cell_type> ] ) has been confirmed .


Furthermore , in the absence of exogenous HGFs , FL monocytic progenitors ( colony-forming unit monocyte [ CFU-M ] ) generate large colonies exclusively composed of monocytes-macrophages ; these colonies are absent in FCS- clonogenic culture .

Furthermore , in the absence of exogenous <protein>HGFs</protein> , <cell_type>FL monocytic progenitors</cell_type> ( <cell_type>colony-forming unit monocyte</cell_type> [ <cell_type>CFU-M</cell_type> ] ) generate large colonies exclusively composed of monocytes-macrophages ; these colonies are absent in FCS- clonogenic culture .


On this basis , we have investigated the role of all-trans retinoic acid ( ATRA ) and its isomer 9-cis RA in FL hematopoiesis .


Both compounds modulate the growth of purified FL HPCs , which show a dose-dependent shift from mixed/erythroid/monocytic to granulocytic colony formation .

Both compounds modulate the growth of <cell_line>purified FL HPCs</cell_line> , which show a dose-dependent shift from mixed/erythroid/monocytic to granulocytic colony formation .


Studies on unicellular and paired daughter cell culture unequivocally indicate that the shift is mediated by modulation of the HPC differentiation program to the granulopoietic pathway ( rather than RA-induced down-modulation of multipotent /erythroid/monocytic HPC growth coupled with recruitment of granulocytic HPCs ) .

Studies on <cell_line>unicellular and paired daughter cell culture</cell_line> unequivocally indicate that the shift is mediated by modulation of the HPC differentiation program to the granulopoietic pathway ( rather than RA-induced down-modulation of multipotent /erythroid/monocytic HPC growth coupled with recruitment of <cell_type>granulocytic HPCs</cell_type> ) .


ATRA and 9-cis RA also exert their effect on the proliferation of primitive HPCs ( high-proliferative potential colony-forming cells [ HPP-CFCs ] ) and putative hematopoietic stem cells ( HSCs ; assayed in Dexter-type long-term culture ) .

ATRA and 9-cis RA also exert their effect on the proliferation of <cell_type>primitive HPCs</cell_type> ( <cell_line>high-proliferative potential colony-forming cells</cell_line> [ <cell_line>HPP-CFCs</cell_line> ] ) and <cell_type>putative hematopoietic stem cells</cell_type> ( <cell_type>HSCs</cell_type> ; assayed in Dexter-type long-term culture ) .


High concentrations of either compound ( 1 ) drastically reduced the number of primary HPP-CFC colonies and totally abolished their recloning capacity and ( 2 ) inhibited HSC proliferation .

High concentrations of either compound ( 1 ) drastically reduced the number of primary <cell_line>HPP-CFC colonies</cell_line> and totally abolished their recloning capacity and ( 2 ) inhibited <cell_type>HSC</cell_type> proliferation .


It is crucial that these results mirror recent observations indicating that murine adult HPCs transduced with dominant negative ATRA receptor ( RAR ) gene are immortalized and show a selective blockade of granulocytic differentiation .

It is crucial that these results mirror recent observations indicating that murine adult <cell_type>HPCs</cell_type> transduced with dominant negative <dna>ATRA receptor ( RAR ) gene</dna> are immortalized and show a selective blockade of granulocytic differentiation .


Altogether , these results suggest that ATRA/9-cis RA may play a key role in FL hematopoiesis via a dual effect hypothetically mediated by interaction with the RAR/RXR heterodimer , ie , inhibition of HSC/ primitive HPC proliferation and induction of CFU-GEMM/ BFU-E/CFU-M shift from the multipotent/erythroid/monocytic to the granulocytic-neutrophilic differentiation program .

Altogether , these results suggest that ATRA/9-cis RA may play a key role in FL hematopoiesis via a dual effect hypothetically mediated by interaction with the <protein>RAR/RXR heterodimer</protein> , ie , inhibition of <cell_line>HSC/ primitive HPC</cell_line> proliferation and induction of CFU-GEMM/ BFU-E/CFU-M shift from the multipotent/erythroid/monocytic to the granulocytic-neutrophilic differentiation program .


Dexamethasone suppression test : corticosteroid receptors regulation in mononuclear leukocytes of young and aged subjects .

Dexamethasone suppression test : <protein>corticosteroid receptors</protein> regulation in <cell_type>mononuclear leukocytes</cell_type> of young and aged subjects .


The dexamethasone suppression test ( DST ) is considered an indicator of the function of the adrenal pituitary axis .


The effect of the steroid is mediated by its binding to corticosteroid receptors .

The effect of the steroid is mediated by its binding to <protein>corticosteroid receptors</protein> .


We previously suggested that the measurement of corticosteroid receptors in lymphocytes is an index of an analogous pattern in brain .

We previously suggested that the measurement of <protein>corticosteroid receptors</protein> in <cell_type>lymphocytes</cell_type> is an index of an analogous pattern in brain .


In the present study , corticosteroid Type I and Type II receptors in mononuclear leukocytes were measured in 10 elderly subjects and in 9 young adults , before and after overnight DST ( 1 mg ) .

In the present study , <protein>corticosteroid Type I and Type II receptors</protein> in <cell_type>mononuclear leukocytes</cell_type> were measured in 10 elderly subjects and in 9 young adults , before and after overnight DST ( 1 mg ) .


Receptors were measured by radioreceptor assay .


In all the subjects , dexamethasone was able to suppress plasma cortisol .


The number of Type I and Type II receptors before the test was lower in elderly subjects than in adults .

The number of <protein>Type I and Type II receptors</protein> before the test was lower in elderly subjects than in adults .


In the control group , dexamethasone produced a significant depression of Type I receptors ( from 267 +/- 72 to 169 +/- 71 receptors per cell ) , which can be interpreted as a primary involvement of Type I receptors in the response to dexamethasone ; Type II receptors decreased in half the subjects ( from 2849 +/- 703 to 2345 +/- 569 receptors per cell ) .

In the control group , dexamethasone produced a significant depression of <protein>Type I receptors</protein> ( from 267 +/- 72 to 169 +/- 71 receptors per cell ) , which can be interpreted as a primary involvement of <protein>Type I receptors</protein> in the response to dexamethasone ; <protein>Type II receptors</protein> decreased in half the subjects ( from 2849 +/- 703 to 2345 +/- 569 receptors per cell ) .


In elderly healthy subjects , Type II receptors were also significantly decreased ( from 1796 +/- 671 to 720 +/- 345 ) .

In elderly healthy subjects , <protein>Type II receptors</protein> were also significantly decreased ( from 1796 +/- 671 to 720 +/- 345 ) .


We suggest that in young subjects Type II receptors are initially up-regulated by dexamethasone , and then down-regulated , while in aged subjects an up-regulation can not be achieved , as suggested by the higher values of plasma cortisol usually found in aging subjects .

We suggest that in young subjects <protein>Type II receptors</protein> are initially up-regulated by dexamethasone , and then down-regulated , while in aged subjects an up-regulation can not be achieved , as suggested by the higher values of plasma cortisol usually found in aging subjects .


Analysis of the ligand-binding domain of human retinoic acid receptor alpha by site-directed mutagenesis .

Analysis of the <protein>ligand-binding domain</protein> of <protein>human retinoic acid receptor alpha</protein> by site-directed mutagenesis .


Three subtypes of retinoic acid receptors ( RAR ) , termed RAR alpha , RAR beta , and RAR gamma , have been described .

Three subtypes of <protein>retinoic acid receptors</protein> ( <protein>RAR</protein> ) , termed <protein>RAR alpha</protein> , <protein>RAR beta</protein> , and <protein>RAR gamma</protein> , have been described .


They are composed of different structural domains , including distinct domains for DNA and ligand binding .

They are composed of different <protein>structural domains</protein> , including distinct domains for DNA and ligand binding .


RARs specifically bind all-trans-retinoic acid ( RA ) , 9-cis-RA , and retinoid analogs .

<protein>RARs</protein> specifically bind all-trans-retinoic acid ( RA ) , 9-cis-RA , and retinoid analogs .


In this study , we examined the functional role of cysteine and arginine residues in the ligand-binding domain of hRAR alpha ( hRAR alpha-LBD , amino acids 154 to 462 ) .

In this study , we examined the functional role of cysteine and arginine residues in the <protein>ligand-binding domain</protein> of <protein>hRAR alpha</protein> ( <protein>hRAR alpha-LBD</protein> , <protein>amino acids 154 to 462</protein> ) .


All conserved cysteine and arginine residues in this domain were mutated by site-directed mutagenesis , and the mutant proteins were characterized by blocking reactions , ligand-binding experiments , transactivation assays , and protease mapping .

All conserved cysteine and arginine residues in this domain were mutated by site-directed mutagenesis , and the <protein>mutant proteins</protein> were characterized by blocking reactions , ligand-binding experiments , transactivation assays , and <protein>protease</protein> mapping .


Changes of any cysteine residue of the hRAR alpha-LBD had no significant influence on the binding of all-trans RA or 9-cis RA .

Changes of any cysteine residue of the <protein>hRAR alpha-LBD</protein> had no significant influence on the binding of all-trans RA or 9-cis RA .


Interestingly , residue C-235 is specifically important in antagonist binding .


With respect to arginine residues , only the two single mutations of R-276 and R-394 to alanine showed a dramatic decrease of agonist and antagonist binding whereas the R272A mutation showed only a slight effect .


For all other arginine mutations , no differences in affinity were detectable .


The two mutations R217A and R294A caused an increased binding efficiency for antagonists but no change in agonist binding .


From these results , we can conclude that electrostatic interactions of retinoids with the RAR alpha-LBD play a significant role in ligand binding .

From these results , we can conclude that electrostatic interactions of retinoids with the <protein>RAR alpha-LBD</protein> play a significant role in ligand binding .


In addition , antagonists show distinctly different requirements for efficient binding , which may contribute to their interference in the ligand-inducible transactivation function of RAR alpha .

In addition , antagonists show distinctly different requirements for efficient binding , which may contribute to their interference in the ligand-inducible transactivation function of <protein>RAR alpha</protein> .


IL4 and IL13 receptors share the gamma c chain and activate STAT6 , STAT3 and STAT5 proteins in normal human B cells .

<protein>IL4 and IL13 receptors</protein> share the <protein>gamma c chain</protein> and activate <protein>STAT6 , STAT3 and STAT5 proteins</protein> in <cell_type>normal human B cells</cell_type> .


IL13 induces the same biological effects as IL4 in normal human B cells .

<protein>IL13</protein> induces the same biological effects as <protein>IL4</protein> in <cell_type>normal human B cells</cell_type> .


We show that as in the IL4R complex , both IL4R alpha and IL2R gamma c are components of the IL13R and that both cytokines induced STAT6 , STAT3 and STAT5 activation in B cells .

We show that as in the <protein>IL4R complex</protein> , both <protein>IL4R alpha</protein> and <protein>IL2R gamma c</protein> are components of the <protein>IL13R</protein> and that both <protein>cytokines</protein> induced <protein>STAT6</protein> , <protein>STAT3</protein> and <protein>STAT5</protein> activation in <cell_type>B cells</cell_type> .


In spite of this similar downstream signalling , IL4 and IL13 used a different set of Janus kinases : IL13 is unable to activate JAK1 and JAK3 .

In spite of this similar downstream signalling , <protein>IL4</protein> and <protein>IL13</protein> used a different set of <protein>Janus kinases</protein> : <protein>IL13</protein> is unable to activate <protein>JAK1</protein> and <protein>JAK3</protein> .


Calcineurin mutants render T lymphocytes resistant to cyclosporin A .

<protein>Calcineurin mutants</protein> render <cell_type>T lymphocytes</cell_type> resistant to cyclosporin A .


The immunosuppressants cyclosporin A ( CsA ) and FK506 have been widely used to prevent and treat graft rejection after human organ and tissue transplantations .


CsA and FK506 associate with intracellular binding proteins ( i.e. , CsA with cyclophilin A and FK506 with FKBP12 ) to form protein/drug complexes that suppress the immune system by preventing activation of T cells in response to antigen presentation .

CsA and FK506 associate with <protein>intracellular binding proteins</protein> ( i.e. , CsA with <protein>cyclophilin A</protein> and FK506 with <protein>FKBP12</protein> ) to form protein/drug complexes that suppress the immune system by preventing activation of <cell_type>T cells</cell_type> in response to antigen presentation .


The common target of CsA and FK506 is calcineurin , a Ca2+/calmodulin-regulated , serine/threonine-specific protein phosphatase that regulates the nuclear import of a transcription factor , NF-AT , required for expression of T cell activation genes .

The common target of CsA and FK506 is <protein>calcineurin</protein> , a <protein>Ca2+/calmodulin-regulated , serine/threonine-specific protein phosphatase</protein> that regulates the nuclear import of a <protein>transcription factor</protein> , <protein>NF-AT</protein> , required for expression of <dna>T cell activation genes</dna> .


In previous studies , we identified calcineurin mutations that block binding by the cyclophilin A/CsA or FKBP12/FK506 complexes and thereby render yeast cells resistant to the antifungal effects of CsA or FK506 .

In previous studies , we identified <protein>calcineurin</protein> mutations that block binding by the <protein>cyclophilin A/CsA or FKBP12/FK506 complexes</protein> and thereby render yeast cells resistant to the antifungal effects of CsA or FK506 .


In this report , we demonstrate that the corresponding mutations in murine calcineurin render the T cell receptor signal transduction cascade CsA resistant in human Jurkat T cells .

In this report , we demonstrate that the corresponding mutations in murine <protein>calcineurin</protein> render the <protein>T cell receptor</protein> signal transduction cascade CsA resistant in <cell_line>human Jurkat T cells</cell_line> .


Our findings support the recently determined calcineurin X-ray crystal structure , provide evidence that calcineurin is the only CsA-sensitive component limiting signaling from the T cell receptor to the nucleus , and suggest a means to render cells and tissues resistant to the toxic side effects of CsA and FK506 .

Our findings support the recently determined <protein>calcineurin</protein> X-ray crystal structure , provide evidence that <protein>calcineurin</protein> is the only <protein>CsA-sensitive component</protein> limiting signaling from the <protein>T cell receptor</protein> to the nucleus , and suggest a means to render cells and tissues resistant to the toxic side effects of CsA and FK506 .


Epstein-Barr viral latency is disrupted by the immediate-early BRLF1 protein through a cell-specific mechanism .

Epstein-Barr viral latency is disrupted by the <protein>immediate-early BRLF1 protein</protein> through a cell-specific mechanism .


Epstein-Barr virus ( EBV ) , the causative agent of infectious mononucleosis , is a human herpesvirus associated with epithelial cell malignancies ( nasopharyngeal carcinoma ) as well as B-cell malignancies .


Understanding how viral latency is disrupted is a central issue in herpesvirus biology .


Epithelial cells are the major site of lytic EBV replication within the human host , and viral reactivation occurs in EBV-associated nasopharyngeal carcinomas .


It is known that expression of a single viral immediate-early protein , BZLF1 , is sufficient to initiate the switch from latent to lytic infection in B cells .

It is known that expression of a single <protein>viral immediate-early protein</protein> , <protein>BZLF1</protein> , is sufficient to initiate the switch from latent to lytic infection in <cell_type>B cells</cell_type> .


Cellular regulation of BZLF1 transcription is therefore thought to play a key role in regulating the stringency of viral latency .

Cellular regulation of <protein>BZLF1</protein> transcription is therefore thought to play a key role in regulating the stringency of viral latency .


Here we show that , unexpectedly , expression of another viral immediate-early protein , BRLF1 , can disrupt viral latency in an epithelial cell-specific fashion .

Here we show that , unexpectedly , expression of another <protein>viral immediate-early protein</protein> , <protein>BRLF1</protein> , can disrupt viral latency in an epithelial cell-specific fashion .


Therefore , the mechanisms leading to disruption of EBV latency appear to be cell-type specific .


Eosinophil priming by cytokines : from cellular signal to in vivo modulation .

<cell_type>Eosinophil</cell_type> priming by <protein>cytokines</protein> : from cellular signal to in vivo modulation .


Eosinophils play an important role in the effector phase of allergic inflammation .

<cell_type>Eosinophils</cell_type> play an important role in the effector phase of allergic inflammation .


This review will focus on the conversion of the unprimed eosinophil phenotype in the peripheral blood of normal individuals to the primed phenotype found in the peripheral blood and tissues of allergic patients , a phenomenon called priming .


Recent data on the signals initiated after cytokine receptor activation on eosinophils will be reviewed .

Recent data on the signals initiated after <protein>cytokine receptor</protein> activation on <cell_type>eosinophils</cell_type> will be reviewed .


CTL recognition of an altered peptide associated with asparagine bond rearrangement .


Implications for immunity and vaccine design .


The extent to which peptides containing chemically and post-translationally modified amino acid side chains are recognized by primed CTL has not been clearly defined .

The extent to which peptides containing chemically and post-translationally modified <protein>amino acid side chains</protein> are recognized by <cell_line>primed CTL</cell_line> has not been clearly defined .


We report on the CTL recognition of a MHC class I-restricted peptide containing a cyclized asparagine ( succinimide ) residue .


This modification of the asparagine side chain is a common intermediate structure during deamidation , isomerization , and bond rearrangements of amide-containing amino acids and also occurs as a side reaction in peptide synthesis .


The CTL specifically recognized the succinimide-containing peptide showing only weak cross-reactivity at high concentrations of the parent peptide containing unmodified asparagine .

The <cell_type>CTL</cell_type> specifically recognized the succinimide-containing peptide showing only weak cross-reactivity at high concentrations of the parent peptide containing unmodified asparagine .


Similarly , CTL raised against the parent peptide did not recognize the succinimide derivative of this peptide .

Similarly , <cell_type>CTL</cell_type> raised against the parent peptide did not recognize the succinimide derivative of this peptide .


Naturally processed forms of these structures are likely to occur given the importance and frequency of deamidation both in vitro and in vivo .


Moreover , since succinimide intermediates of deamidated peptides can occasionally be very stable , these peptides have the potential to act as altered self-Ags with significant implications for autoimmunity .


In addition , unwanted and potentially hazardous specificities may be elicited when using synthetic peptides in subunit vaccines in which succinimide residues may form spontaneously during storage or chemical synthesis .


A 3 ' -- > 5 ' XPB helicase defect in repair/transcription factor TFIIH of xeroderma pigmentosum group B affects both DNA repair and transcription .

A 3 ' -- > 5 ' <protein>XPB helicase</protein> defect in <protein>repair/transcription factor</protein> <protein>TFIIH</protein> of xeroderma pigmentosum group B affects both DNA repair and transcription .


XPB is a subunit of the basal transcription factor TFIIH , which is also involved in nucleotide excision repair ( NER ) and potentially in cell cycle regulation .

<protein>XPB</protein> is a subunit of the basal <protein>transcription factor</protein> <protein>TFIIH</protein> , which is also involved in nucleotide excision repair ( NER ) and potentially in cell cycle regulation .


A frameshift mutation in the 3'-end of the XPB gene is responsible for a concurrence of two disorders : xeroderma pigmentosum ( XP ) and Cockayne 's syndrome ( CS ) .

A frameshift mutation in the 3'-end of the <dna>XPB gene</dna> is responsible for a concurrence of two disorders : xeroderma pigmentosum ( XP ) and Cockayne 's syndrome ( CS ) .


We have isolated TFIIH from cells derived from a patient ( XP11BE ) who carries this frameshift mutation ( TFIIHmut ) and from the mother of this patient ( TFIIHwt ) to determine the biochemical consequences of the mutation .

We have isolated <protein>TFIIH</protein> from cells derived from a patient ( XP11BE ) who carries this frameshift mutation ( <protein>TFIIHmut</protein> ) and from the mother of this patient ( <protein>TFIIHwt</protein> ) to determine the biochemical consequences of the mutation .


Although identical in composition and stoichiometry to TFIIHwt , TFIIHmut shows a reduced 3 ' -- > 5 ' XPB helicase activity .

Although identical in composition and stoichiometry to <protein>TFIIHwt</protein> , <protein>TFIIHmut</protein> shows a reduced 3 ' -- > 5 ' <protein>XPB</protein> helicase activity .


A decrease in helicase and DNA-dependent ATPase activities was also observed with the mutated recombinant XPB protein .

A decrease in helicase and <protein>DNA-dependent ATPase</protein> activities was also observed with the mutated recombinant <protein>XPB protein</protein> .


The XPB mutation causes a severe NER defect .

The <protein>XPB</protein> mutation causes a severe NER defect .


In addition , we provide evidence for a decrease in basal transcription activity in vitro .


The latter defect may provide an explanation for many of the XP and CS symptoms that are difficult to rationalize based solely on an NER defect .


Thus , this work presents the first detailed analysis of a naturally occurring mutation in a basal transcription factor and supports the concept that the combined XP/CS clinical entity is actually the result of a combined transcription/repair deficiency .

Thus , this work presents the first detailed analysis of a naturally occurring mutation in a <protein>basal transcription factor</protein> and supports the concept that the combined XP/CS clinical entity is actually the result of a combined transcription/repair deficiency .


The Ets protein Spi-B is expressed exclusively in B cells and T cells during development .

The Ets protein <protein>Spi-B</protein> is expressed exclusively in <cell_type>B cells</cell_type> and <cell_type>T cells</cell_type> during development .


Spi-B and PU.1 are hematopoietic-specific transcription factors that constitute a subfamily of the Ets family of DNA-binding proteins .

<protein>Spi-B</protein> and <protein>PU.1</protein> are <protein>hematopoietic-specific transcription factors</protein> that constitute a subfamily of the <protein>Ets family</protein> of <protein>DNA-binding proteins</protein> .


Here we show that contrary to previous reports , PU.1 and Spi-B have very different expression patterns .

Here we show that contrary to previous reports , <protein>PU.1</protein> and <protein>Spi-B</protein> have very different expression patterns .


PU.1 is expressed at high levels in B cells , mast cells , megakaryocytes , macrophages , neutrophils , and immature erythroid cells and at lower levels in mature erythrocytes .

<protein>PU.1</protein> is expressed at high levels in <cell_type>B cells</cell_type> , <cell_type>mast cells</cell_type> , <cell_type>megakaryocytes</cell_type> , <cell_type>macrophages</cell_type> , <cell_type>neutrophils</cell_type> , and <cell_type>immature erythroid cells</cell_type> and at lower levels in <cell_type>mature erythrocytes</cell_type> .


PU.1 is completely absent from peripheral T cells and most T cell lines based on sensitive RT-PCR assays .

<protein>PU.1</protein> is completely absent from <cell_type>peripheral T cells</cell_type> and most <cell_line>T cell lines</cell_line> based on sensitive RT-PCR assays .


In contrast , Spi-B is expressed exclusively in lymphoid cells and can be detected in early fetal thymus and spleen .

In contrast , <protein>Spi-B</protein> is expressed exclusively in <cell_type>lymphoid cells</cell_type> and can be detected in early fetal thymus and spleen .


In situ hybridizations of adult murine tissues demonstrate Spi-B mRNA in the medulla of the thymus , the white pulp of the spleen , and the germinal centers of lymph nodes .

In situ hybridizations of adult murine tissues demonstrate <rna>Spi-B mRNA</rna> in the medulla of the thymus , the white pulp of the spleen , and the germinal centers of lymph nodes .


Spi-B expression is very abundant in B cells and both Spi-B mRNA and protein are detected in some T cells .

<protein>Spi-B</protein> expression is very abundant in <cell_type>B cells</cell_type> and both <rna>Spi-B mRNA</rna> and protein are detected in some <cell_type>T cells</cell_type> .


In situ hybridization and Northern blot analysis suggest that Spi-B gene expression increases during B cell maturation and decreases during T cell maturation .

In situ hybridization and Northern blot analysis suggest that <protein>Spi-B</protein> gene expression increases during B cell maturation and decreases during T cell maturation .


Gel-retardation experiments show that Spi-B can bind to all putative PU.1 binding sites , but do not reveal any preferred Spi-B binding site .

Gel-retardation experiments show that <protein>Spi-B</protein> can bind to all <dna>putative PU.1 binding sites</dna> , but do not reveal any preferred <dna>Spi-B binding site</dna> .


Finally , both PU.1 and Spi-B function as transcriptional activators of the immunoglobulin light-chain enhancer E lambda 2.4 when coexpressed with Pip ( PU.1-interaction partner ) in NIH-3T3 cells .

Finally , both <protein>PU.1</protein> and <protein>Spi-B</protein> function as transcriptional activators of the <dna>immunoglobulin light-chain enhancer E lambda 2.4</dna> when coexpressed with <protein>Pip</protein> ( <protein>PU.1-interaction partner</protein> ) in <cell_line>NIH-3T3 cells</cell_line> .


Taken together , these data suggest that differences in patterns of expression between Spi-B and PU.1 distinguish the function of each protein during development of the immune system .

Taken together , these data suggest that differences in patterns of expression between <protein>Spi-B</protein> and <protein>PU.1</protein> distinguish the function of each protein during development of the immune system .


A critical role of Sp1- and Ets-related transcription factors in maintaining CTL-specific expression of the mouse perforin gene .

A critical role of <protein>Sp1- and Ets-related transcription factors</protein> in maintaining CTL-specific expression of the <dna>mouse perforin gene</dna> .


This study was designed to determine the potential cis-elements involved in transcriptional regulation of the mouse perforin gene .

This study was designed to determine the potential <dna>cis-elements</dna> involved in transcriptional regulation of the <dna>mouse perforin gene</dna> .


DNase I hypersensitive site ( DHS ) mapping revealed that the perforin locus contained six DHS within 7.0 kb of the 5 ' upstream sequence ( -7.0 kb ) and two DHS in intron 2 .

<dna>DNase I hypersensitive site</dna> ( <dna>DHS</dna> ) mapping revealed that the <dna>perforin locus</dna> contained six <dna>DHS</dna> within 7.0 kb of the <dna>5 ' upstream sequence</dna> ( -7.0 kb ) and two <dna>DHS</dna> in <dna>intron 2</dna> .


The six 5 ' upstream and one intronic DHS were detected in only perforin-expressing lymphocytes .

The six <dna>5 ' upstream</dna> and one <dna>intronic DHS</dna> were detected in only <cell_type>perforin-expressing lymphocytes</cell_type> .


Chloramphenicol acetyltransferase ( CAT ) activities directed by 5 ' upstream promoter were detected preferentially in perforin-expressing cell lines .

<protein>Chloramphenicol acetyltransferase</protein> ( <protein>CAT</protein> ) activities directed by <dna>5 ' upstream promoter</dna> were detected preferentially in <cell_line>perforin-expressing cell lines</cell_line> .


A construct termed PFP5a containing -795 bp exhibited the highest CAT activity , and PFP9a20 containing only -73 bp also produced significantly high CAT activity in CTLL-R8 cells .

A construct termed <dna>PFP5a</dna> containing <dna>-795 bp</dna> exhibited the highest <protein>CAT</protein> activity , and <dna>PFP9a20</dna> containing only <dna>-73 bp</dna> also produced significantly high <protein>CAT</protein> activity in <cell_line>CTLL-R8 cells</cell_line> .


The proximal region in PFP9a20 contained two potential Sp1 binding sites ( GC box and GT box ) and one Ets binding site ( EBS ) .

The <dna>proximal region</dna> in <dna>PFP9a20</dna> contained two potential <dna>Sp1 binding sites</dna> ( <dna>GC box</dna> and <dna>GT box</dna> ) and one <dna>Ets binding site</dna> ( <dna>EBS</dna> ) .


Electrophoretic mobility shift assay showed that each of the cis-elements bound specific protein factors .

Electrophoretic mobility shift assay showed that each of the <dna>cis-elements</dna> bound specific <protein>protein factors</protein> .


When single-point mutation was introduced to each GC box , EBS , and GT box in PFP9a20 , at least 3-fold less CAT activity was observed in CTLL-R8 cells .

When single-point mutation was introduced to each <dna>GC box</dna> , <dna>EBS</dna> , and <dna>GT box</dna> in <dna>PFP9a20</dna> , at least 3-fold less <protein>CAT</protein> activity was observed in <cell_line>CTLL-R8 cells</cell_line> .


To confirm the importance of the three cis-acting elements in the perforin gene expression , point mutation was introduced again to each proximal GC box , EBS , and GT box of PFP5a .

To confirm the importance of the three <dna>cis-acting elements</dna> in the <dna>perforin gene</dna> expression , point mutation was introduced again to each <dna>proximal GC box</dna> , <dna>EBS</dna> , and <dna>GT box</dna> of <dna>PFP5a</dna> .


The point mutations resulted in a 2.5- to 3-fold reduction of CAT activity .

The point mutations resulted in a 2.5- to 3-fold reduction of <protein>CAT</protein> activity .


The results suggest that a combination of the three proximal cis-acting elements may constitute a minimal region responsible for CTL-specific expression of perforin .

The results suggest that a combination of the three proximal <dna>cis-acting elements</dna> may constitute a minimal region responsible for CTL-specific expression of <protein>perforin</protein> .


The Oct-2 transcription factor .

The <protein>Oct-2 transcription factor</protein> .


The Oct-2 transcription factor is a member of the POU ( Pit-Oct-Unc ) family of transcription factors and is expressed only in B lymphocytes and in neuronal cells but not in other cell types .

The <protein>Oct-2 transcription factor</protein> is a member of the <protein>POU ( Pit-Oct-Unc ) family</protein> of <protein>transcription factors</protein> and is expressed only in <cell_type>B lymphocytes</cell_type> and in <cell_type>neuronal cells</cell_type> but not in other cell types .


The primary RNA transcript of the gene is subject to alternative splicing to yield different variants which can either activate or repress gene expression .

The <rna>primary RNA transcript</rna> of the gene is subject to alternative splicing to yield different variants which can either activate or repress gene expression .


The forms produced in B lymphocytes have a predominantly activating effect on gene expression whereas those produced in neuronal cells have a predominantly inhibitory effect and can repress the expression of both the herpes simplex virus immediate-early genes and the cellular tyrosine hydroxylase gene .

The forms produced in <cell_type>B lymphocytes</cell_type> have a predominantly activating effect on gene expression whereas those produced in <cell_type>neuronal cells</cell_type> have a predominantly inhibitory effect and can repress the expression of both the <dna>herpes simplex virus immediate-early genes</dna> and the <dna>cellular tyrosine hydroxylase gene</dna> .


Thus Oct-2 plays an important role in the regulation of cellular gene expression in both B cells and neuronal cells as well as in the control of viral latency .

Thus <protein>Oct-2</protein> plays an important role in the regulation of cellular gene expression in both <cell_type>B cells</cell_type> and <cell_type>neuronal cells</cell_type> as well as in the control of viral latency .


Cell-type-specific regulation of the human tumor necrosis factor alpha gene in B cells and T cells by NFATp and ATF-2/JUN .

Cell-type-specific regulation of the <dna>human tumor necrosis factor alpha gene</dna> in <cell_type>B cells</cell_type> and <cell_type>T cells</cell_type> by <protein>NFATp</protein> and <protein>ATF-2/JUN</protein> .


The human tumor necrosis factor alpha ( TNF-alpha ) gene is one of the earliest genes transcribed after the stimulation of a B cell through its antigen receptor or via the CD-40 pathway .

The <dna>human tumor necrosis factor alpha ( TNF-alpha ) gene</dna> is one of the earliest genes transcribed after the stimulation of a <cell_type>B cell</cell_type> through its <protein>antigen receptor</protein> or via the CD-40 pathway .


In both cases , induction of TNF-alpha gene transcription can be blocked by the immunosuppressants cyclosporin A and FK506 , which suggested a role for the NFAT family of proteins in the regulation of the gene in B cells .

In both cases , induction of <dna>TNF-alpha gene</dna> transcription can be blocked by the immunosuppressants cyclosporin A and FK506 , which suggested a role for the <protein>NFAT family</protein> of proteins in the regulation of the gene in <cell_type>B cells</cell_type> .


Furthermore , in T cells , two molecules of NFATp bind to the TNF-alpha promoter element kappa 3 in association with ATF-2 and Jun proteins bound to an immediately adjacent cyclic AMP response element ( CRE ) site .

Furthermore , in <cell_type>T cells</cell_type> , two molecules of <protein>NFATp</protein> bind to the <dna>TNF-alpha promoter element kappa 3</dna> in association with <protein>ATF-2</protein> and <protein>Jun proteins</protein> bound to an immediately adjacent <dna>cyclic AMP response element ( CRE ) site</dna> .


Here , using the murine B-cell lymphoma cell line A20 , we show that the TNF-alpha gene is regulated in a cell-type-specific manner .

Here , using the <cell_line>murine B-cell lymphoma cell line</cell_line> <cell_line>A20</cell_line> , we show that the <dna>TNF-alpha gene</dna> is regulated in a cell-type-specific manner .


In A20 B cells , the TNF-alpha gene is not regulated by NFATp bound to the kappa 3 element .

In <cell_line>A20 B cells</cell_line> , the <dna>TNF-alpha gene</dna> is not regulated by <protein>NFATp</protein> bound to the <dna>kappa 3 element</dna> .


Instead , ATF-2 and Jun proteins bind to the composite kappa 3/CRE site and NFATp binds to a newly identified second NFAT site centered at -76 nucleotides relative to the TNF-alpha transcription start site .

Instead , <protein>ATF-2</protein> and <protein>Jun proteins</protein> bind to the <dna>composite kappa 3/CRE site</dna> and <protein>NFATp</protein> binds to a newly identified second <dna>NFAT site</dna> centered at <dna>-76 nucleotides</dna> relative to the <dna>TNF-alpha transcription start site</dna> .


This new site plays a critical role in the calcium-mediated , cyclosporin A-sensitive induction of TNF-alpha in both A20 B cells and Ar-5 cells .

This new site plays a critical role in the calcium-mediated , cyclosporin A-sensitive induction of <protein>TNF-alpha</protein> in both <cell_line>A20 B cells</cell_line> and <cell_line>Ar-5 cells</cell_line> .


Consistent with these results , quantitative DNase footprinting of the TNF-alpha promoter using increasing amounts of recombinant NFATp demonstrated that the -76 site binds to NFATp with a higher affinity than the kappa 3 site .

Consistent with these results , quantitative <protein>DNase</protein> footprinting of the <dna>TNF-alpha promoter</dna> using increasing amounts of recombinant <protein>NFATp</protein> demonstrated that the <dna>-76 site</dna> binds to <protein>NFATp</protein> with a higher affinity than the <dna>kappa 3 site</dna> .


Two other previously unrecognized NFATp-binding sites in the proximal TNF-alpha promoter were also identified by this analysis .

Two other previously unrecognized <dna>NFATp-binding sites</dna> in the proximal <dna>TNF-alpha promoter</dna> were also identified by this analysis .


Thus , through the differential use of the same promoter element , the composite kappa 3/CRE site , the TNF-alpha gene is regulated in a cell-type-specific manner in response to the same extracellular signal .

Thus , through the differential use of the same <dna>promoter element</dna> , the <dna>composite kappa 3/CRE site</dna> , the <dna>TNF-alpha gene</dna> is regulated in a cell-type-specific manner in response to the same extracellular signal .


Activation of Stat 5b in erythroid progenitors correlates with the ability of ErbB to induce sustained cell proliferation .

Activation of <protein>Stat 5b</protein> in <cell_type>erythroid progenitors</cell_type> correlates with the ability of <protein>ErbB</protein> to induce sustained cell proliferation .


Self renewal of normal erythroid progenitors is induced by the receptor tyrosine kinase c-ErbB , whereas other receptors ( c-Kit/Epo-R ) regulate erythroid differentiation .

Self renewal of normal <cell_type>erythroid progenitors</cell_type> is induced by the <protein>receptor tyrosine kinase</protein> <protein>c-ErbB</protein> , whereas other <protein>receptors</protein> ( <protein>c-Kit/Epo-R</protein> ) regulate erythroid differentiation .


To address possible mechanisms that could explain this selective activity of c-ErbB , we analyzed the ability of these receptors to activate the different members of the Stat transcription factor family .

To address possible mechanisms that could explain this selective activity of <protein>c-ErbB</protein> , we analyzed the ability of these receptors to activate the different members of the <protein>Stat transcription factor family</protein> .


Ligand activation of c-ErbB induced the tyrosine phosphorylation , DNA-binding , and reporter gene transcription of Stat 5b in erythroblasts .

Ligand activation of <protein>c-ErbB</protein> induced the tyrosine phosphorylation , DNA-binding , and <dna>reporter gene</dna> transcription of <protein>Stat 5b</protein> in <cell_type>erythroblasts</cell_type> .


In contrast , ligand activation of c-Kit was unable to induce any of these effects in the same cells .

In contrast , ligand activation of <protein>c-Kit</protein> was unable to induce any of these effects in the same cells .


Activation of the erythropoietin receptor caused specific DNA-binding of Stat 5b , but failed to induce reporter gene transcription .

Activation of the <protein>erythropoietin receptor</protein> caused specific DNA-binding of <protein>Stat 5b</protein> , but failed to induce <dna>reporter gene</dna> transcription .


These biochemical findings correlate perfectly with the selective ability of c-ErbB to cause sustained self renewal in erythroid progenitors .

These biochemical findings correlate perfectly with the selective ability of <protein>c-ErbB</protein> to cause sustained self renewal in <cell_type>erythroid progenitors</cell_type> .


Defective transcription of the IL-2 gene is associated with impaired expression of c-Fos , FosB , and JunB in anergic T helper 1 cells .

Defective transcription of the <dna>IL-2 gene</dna> is associated with impaired expression of <protein>c-Fos</protein> , <protein>FosB</protein> , and <protein>JunB</protein> in <cell_line>anergic T helper 1 cells</cell_line> .


Anergic CD4+ Th cells do not produce IL-2 when challenged with Ag-pulsed accessory cells because of a transcriptional defect .

<cell_line>Anergic CD4+ Th cells</cell_line> do not produce <protein>IL-2</protein> when challenged with <cell_line>Ag-pulsed accessory cells</cell_line> because of a transcriptional defect .


In this work , we report that these anergic T cells are defective in their ability to up-regulate protein binding and transactivation at two critical IL-2 DNA enhancer elements : NF-AT ( nuclear factor of activated T cells ; a sequence that binds a heterotrimeric NFATp , Fos , and Jun protein complex ) and Activator Protein-1 ( AP-1 ) ( that binds Fos and Jun heterodimers ) .

In this work , we report that these <cell_line>anergic T cells</cell_line> are defective in their ability to up-regulate protein binding and transactivation at two critical <dna>IL-2 DNA enhancer elements</dna> : <protein>NF-AT</protein> ( <protein>nuclear factor of activated T cells</protein> ; a sequence that binds a <protein>heterotrimeric NFATp , Fos , and Jun protein complex</protein> ) and <protein>Activator Protein-1</protein> ( <protein>AP-1</protein> ) ( that binds <protein>Fos and Jun heterodimers</protein> ) .


Western blot analysis of nuclear extracts showed that the impaired DNA-protein interactions in anergic T cells were associated with poor expression of the inducible AP-1 family members c-Fos , FosB , and JunB .

Western blot analysis of nuclear extracts showed that the impaired DNA-protein interactions in <cell_line>anergic T cells</cell_line> were associated with poor expression of the inducible <protein>AP-1</protein> family members <protein>c-Fos</protein> , <protein>FosB</protein> , and <protein>JunB</protein> .


However , the reduced expression of these proteins was not the result of a global TCR/CD3 -signaling defect because CD3 cross-linking induced an equivalent increase in intracellular-free calcium ions , as well as NFATp dephosphorylation , translocation to the nucleus , and DNA binding in both normal and anergic T cells .

However , the reduced expression of these proteins was not the result of a global <protein>TCR/CD3</protein> -signaling defect because <protein>CD3</protein> cross-linking induced an equivalent increase in intracellular-free calcium ions , as well as <protein>NFATp</protein> dephosphorylation , translocation to the nucleus , and DNA binding in both <cell_type>normal</cell_type> and <cell_line>anergic T cells</cell_line> .


Thus , defective IL-2 gene transcription appears to be due , at least in part , to a selective block in the expression of the AP-1 Fos and Jun family members in anergic T cells .

Thus , defective <dna>IL-2 gene</dna> transcription appears to be due , at least in part , to a selective block in the expression of the <protein>AP-1 Fos and Jun family members</protein> in <cell_line>anergic T cells</cell_line> .


Sequence-specific DNA binding of the B-cell-specific coactivator OCA-B .

Sequence-specific DNA binding of the <protein>B-cell-specific coactivator</protein> <protein>OCA-B</protein> .