Regulation of cell-type-specific interleukin-2 receptor alpha-chain gene expression : potential role of physical interactions between Elf-1 , HMG-I ( Y ) , and NF-kappa B family proteins .

Regulation of cell-type-specific <protein>interleukin-2 receptor alpha-chain</protein> gene expression : potential role of physical interactions between <protein>Elf-1</protein> , <protein>HMG-I ( Y )</protein> , and <protein>NF-kappa B family proteins</protein> .


The interleukin 2 receptor alpha-chain ( IL-2R alpha ) gene is rapidly and potently induced in T cells in response to mitogenic stimuli .

The <dna>interleukin 2 receptor alpha-chain ( IL-2R alpha ) gene</dna> is rapidly and potently induced in <cell_type>T cells</cell_type> in response to mitogenic stimuli .


Previously , an inducible enhancer between nucleotides -299 and -228 that contains NF-kappa B and CArG motifs was identified .

Previously , an <dna>inducible enhancer</dna> between <dna>nucleotides -299 and -228</dna> that contains <dna>NF-kappa B and CArG motifs</dna> was identified .


We now report the characterization of a second essential positive regulatory element located between nucleotides -137 and -64 that binds Elf-1 and HMG-I ( Y ) .

We now report the characterization of a second <dna>essential positive regulatory element</dna> located between <dna>nucleotides -137 and -64</dna> that binds <protein>Elf-1</protein> and <protein>HMG-I ( Y )</protein> .


This element had maximal activity in lymphoid cells , paralleling the cell type specificity of Elf-1 expression .

This element had maximal activity in <cell_type>lymphoid cells</cell_type> , paralleling the cell type specificity of <protein>Elf-1</protein> expression .


Transcription from the IL-2R alpha promoter was inhibited when either the Elf-1 or the HMG-I ( Y ) binding site was mutated .

Transcription from the <dna>IL-2R alpha promoter</dna> was inhibited when either the <dna>Elf-1 or the HMG-I ( Y ) binding site</dna> was mutated .


Coexpression of both proteins activated transcription of the -137 to -64 element in COS-7 cells .

Coexpression of both proteins activated transcription of the <dna>-137 to -64 element</dna> in <cell_line>COS-7 cells</cell_line> .


Elf-1 physically associated with HMG-I and with NF-kappa B p50 and c-Rel in vitro , suggesting that protein-protein interactions might functionally coordinate the actions of the upstream and downstream positive regulatory elements .

<protein>Elf-1</protein> physically associated with <protein>HMG-I</protein> and with <protein>NF-kappa B</protein> <protein>p50</protein> and <protein>c-Rel</protein> in vitro , suggesting that protein-protein interactions might functionally coordinate the actions of the <dna>upstream and downstream positive regulatory elements</dna> .


This is the first report of a physical interaction between an Ets family member and NF-kappa B family proteins .

This is the first report of a physical interaction between an Ets family member and <protein>NF-kappa B family proteins</protein> .


These findings provide significant new insights into the protein-protein and protein-DNA interactions that regulate cell-type-specific and inducible IL-2R alpha gene expression and also have implications for other genes regulated by Elf-1 and NF-kappa B family proteins .

These findings provide significant new insights into the protein-protein and protein-DNA interactions that regulate cell-type-specific and inducible <protein>IL-2R alpha</protein> gene expression and also have implications for other genes regulated by <protein>Elf-1</protein> and <protein>NF-kappa B family proteins</protein> .


Isolation of cDNA clones for 42 different Kruppel-related zinc finger proteins expressed in the human monoblast cell line U-937 .

Isolation of <dna>cDNA clones</dna> for 42 different <protein>Kruppel-related zinc finger proteins</protein> expressed in the <cell_line>human monoblast cell line U-937</cell_line> .


To study the complexity and structural characteristics of zinc finger proteins expressed during human hematopoiesis and to isolate novel regulators of blood cell development , a degenerate oligonucleotide probe specific for a consensus zinc finger peptide domain was used to isolate 63 cDNA clones for Kruppel-related zinc finger genes from the human monoblast cell line U-937 .

To study the complexity and structural characteristics of <protein>zinc finger proteins</protein> expressed during human hematopoiesis and to isolate novel regulators of blood cell development , a degenerate oligonucleotide probe specific for a <protein>consensus zinc finger peptide domain</protein> was used to isolate 63 <dna>cDNA clones</dna> for <dna>Kruppel-related zinc finger genes</dna> from the <cell_line>human monoblast cell line U-937</cell_line> .


By extensive nucleotide sequence and Northern blot analysis , these cDNA clones were found to originate from approximately 42 different genes ( HZF 1-42 ) of which only 8 have previously been described .

By extensive nucleotide sequence and Northern blot analysis , these <dna>cDNA clones</dna> were found to originate from approximately 42 different genes ( <dna>HZF 1-42</dna> ) of which only 8 have previously been described .


Northern blot analysis showed that a majority of these genes were expressed at comparable levels in U-937 and HeLa cells .

Northern blot analysis showed that a majority of these genes were expressed at comparable levels in <cell_line>U-937</cell_line> and <cell_line>HeLa cells</cell_line> .


The large number of individual genes represented among the 63 clones and their apparent non-cell-type-specific expression suggest that the majority of the Kruppel-related zinc finger genes are likely to be expressed in most human tissues .

The large number of individual genes represented among the 63 clones and their apparent non-cell-type-specific expression suggest that the majority of the <dna>Kruppel-related zinc finger genes</dna> are likely to be expressed in most human tissues .


In contrast , some of the genes displayed a restricted expression pattern , indicating that they represent potential regulators of monocyte differentiation or proliferation .


Detailed structural analysis of the first 12 cDNAs ( HZF 1-10 ) and a partial characterization of HZF 11-42 revealed that a common feature of human Kruppel-related zinc finger proteins is the presence of tandem arrays of zinc fingers ranging in number from 3 to over 20 that are preferentially located in the carboxy-terminal regions of the proteins .

Detailed structural analysis of the first 12 <dna>cDNAs</dna> ( <dna>HZF 1-10</dna> ) and a partial characterization of <dna>HZF 11-42</dna> revealed that a common feature of <protein>human Kruppel-related zinc finger proteins</protein> is the presence of tandem arrays of <protein>zinc fingers</protein> ranging in number from 3 to over 20 that are preferentially located in the <protein>carboxy-terminal regions</protein> of the proteins .


In addition , several novel KRAB-containing zinc finger genes and a novel conserved sequence element were identified .

In addition , several novel <dna>KRAB-containing zinc finger genes</dna> and a novel <dna>conserved sequence element</dna> were identified .


CAG repeat length variation in sperm from a patient with Kennedy 's disease .

CAG repeat length variation in <cell_type>sperm</cell_type> from a patient with Kennedy 's disease .


Using a modified sperm typing protocol , the mutation frequency of the CAG repeat region at the androgen receptor locus has been measured using a rare semen sample from an individual with spinal and bulbar muscular atrophy ( SBMA ) .

Using a modified <cell_type>sperm</cell_type> typing protocol , the mutation frequency of the <dna>CAG repeat region</dna> at the <dna>androgen receptor locus</dna> has been measured using a rare semen sample from an individual with spinal and bulbar muscular atrophy ( SBMA ) .


Among 258 X chromosome-containing sperm , 19 % had a repeat number equal to the donor 's somatic DNA ( 47 repeats ) , 66 % were expansions and 15 % were contractions .

Among 258 <cell_type>X chromosome-containing sperm</cell_type> , 19 % had a repeat number equal to the <dna>donor 's somatic DNA</dna> ( 47 repeats ) , 66 % were expansions and 15 % were contractions .


The average expansion was 2.7 repeats .


More than half of the expansions involved one or two repeats ; the largest was 11 repeats .


68 % of the contractions were also one or two repeats but six ( 16 % ) were very large ( 12-25 repeats ) .


One contraction generated an allele in an intermediate size range ( 33-39 repeats ) .


Such alleles have not been observed among more than 900 normal and SBMA X-chromosomes that have been examined .

Such alleles have not been observed among more than 900 normal and <dna>SBMA X-chromosomes</dna> that have been examined .


Comparison of the SBMA sperm typing results with mutation frequency data on normal alleles supports the hypothesis that trinucleotide repeat expansions may have a different molecular origin than contractions .

Comparison of the SBMA <cell_type>sperm</cell_type> typing results with mutation frequency data on normal alleles supports the hypothesis that <dna>trinucleotide repeat</dna> expansions may have a different molecular origin than contractions .


Aspirin-like drugs can protect human T lymphocytes against benzoquinone cytotoxicity : evidence for a NAD ( P ) H : quinone reductase -dependent mechanism .

Aspirin-like drugs can protect <cell_type>human T lymphocytes</cell_type> against benzoquinone cytotoxicity : evidence for a <protein>NAD ( P ) H : quinone reductase</protein> -dependent mechanism .


Benzene toxicity towards lymphocytes is thought to be mediated by metabolites of benzene including benzoquinone ( BQ ) .

Benzene toxicity towards <cell_type>lymphocytes</cell_type> is thought to be mediated by metabolites of benzene including benzoquinone ( BQ ) .


NAD ( P ) H : quinone reductase ( QR ) is known to protect against BQ toxicity .

<protein>NAD ( P ) H : quinone reductase</protein> ( <protein>QR</protein> ) is known to protect against BQ toxicity .


The expression of the QR gene is regulated by the transcription factor AP-1 .

The expression of the <dna>QR gene</dna> is regulated by the <protein>transcription factor</protein> <protein>AP-1</protein> .


We had previously found that aspirin-like drugs ( ALD ) induce AP-1 in human T lymphocytes .

We had previously found that aspirin-like drugs ( ALD ) induce <protein>AP-1</protein> in <cell_type>human T lymphocytes</cell_type> .


It was therefore hypothesized that ALD would protect lymphocytes against BQ toxicity by inducing QR .

It was therefore hypothesized that ALD would protect <cell_type>lymphocytes</cell_type> against BQ toxicity by inducing <protein>QR</protein> .


Molt-4 cells ( M4 ) , a human T lymphocyte cell line , were incubated with different concentrations of two ALD , flurbiprofen and sodium diclofenac , and then exposed to BQ .

<cell_line>Molt-4 cells</cell_line> ( <cell_line>M4</cell_line> ) , a <cell_line>human T lymphocyte cell line</cell_line> , were incubated with different concentrations of two ALD , flurbiprofen and sodium diclofenac , and then exposed to BQ .


Toxicity was measured by viability ( trypan blue exclusion ) .


Both drugs protected the cells against BQ cytotoxicity in a dose-dependent manner , e.g. , sodium diclofenac at 15 microM reduced the fraction of BQ-treated dead cells by 70 % .


ALDs induced QR activity in the M4 cells in the same range of concentrations that protected the cells against BQ toxicity .

ALDs induced <protein>QR</protein> activity in the M4 cells in the same range of concentrations that protected the cells against BQ toxicity .


The protective effect of ALD was significantly reduced by dicoumarol , a QR -specific inhibitor .

The protective effect of ALD was significantly reduced by dicoumarol , a <protein>QR</protein> -specific inhibitor .


Since human T cells and T cell lines do not metabolize arachidonic acid , our data suggest that ALD can protect human T lymphocytes against a metabolite of benzene by induction of QR activity .

Since <cell_type>human T cells</cell_type> and <cell_type>T cell lines</cell_type> do not metabolize arachidonic acid , our data suggest that ALD can protect <cell_type>human T lymphocytes</cell_type> against a metabolite of benzene by induction of <protein>QR</protein> activity .


Correlation of differentiation-inducing activity of retinoids on human leukemia cell lines HL-60 and NB4 .

Correlation of differentiation-inducing activity of retinoids on <cell_line>human leukemia cell lines</cell_line> <cell_line>HL-60</cell_line> and <cell_line>NB4</cell_line> .


Retinoids , including all-trans-retinoic acid , its isomers , and fifty synthetic retinoids ( retinobenzoic acids ) , were tested for differentiation-inducing activity on human leukemia cell lines HL-60 and NB4 .

Retinoids , including all-trans-retinoic acid , its isomers , and fifty synthetic retinoids ( retinobenzoic acids ) , were tested for differentiation-inducing activity on <cell_line>human leukemia cell lines</cell_line> <cell_line>HL-60</cell_line> and <cell_line>NB4</cell_line> .


A good linear correlation , with an r value of 0.91 , between the ED50 values for the differentiation-inducing activity towards HL-60 cells and that towards NB4 cells was found .

A good linear correlation , with an r value of 0.91 , between the ED50 values for the differentiation-inducing activity towards <cell_line>HL-60 cells</cell_line> and that towards <cell_line>NB4 cells</cell_line> was found .


Platelet-activating factor ( PAF ) positively auto-regulates the expression of human PAF receptor transcript 1 ( leukocyte-type ) through NF-kappa B .

<protein>Platelet-activating factor</protein> ( <protein>PAF</protein> ) positively auto-regulates the expression of <protein>human PAF receptor transcript 1</protein> ( leukocyte-type ) through <protein>NF-kappa B</protein> .


The human platelet-activating factor receptor ( PAFR ) gene is transcribed by two distinct promoters ( promoter 1 and promoter 2 ) to generate two transcripts ( designated as PAFR transcript 1 and PAFR transcript 2 ) , though their open reading frames are identical .

The <dna>human platelet-activating factor receptor ( PAFR ) gene</dna> is transcribed by two distinct <dna>promoters</dna> ( <dna>promoter 1</dna> and <dna>promoter 2</dna> ) to generate two transcripts ( designated as <rna>PAFR transcript 1</rna> and <rna>PAFR transcript 2</rna> ) , though their open reading frames are identical .


By primer extension analysis to discriminate two transcripts , we found that the levels of PAFR transcript 1 ( leukocyte-type ) , but not PAFR transcript 2 ( tissue-type ) , are upregulated by PAF as well as by 12-O-tetradecanoylphorbol-13-acetate ( TPA ) in the human stomach cancer cell line ( JR-St cells ) which expresses both functional PAFR transcript 1 and PAFR transcript 2 endogenously .

By primer extension analysis to discriminate two transcripts , we found that the levels of <rna>PAFR transcript 1</rna> ( leukocyte-type ) , but not <rna>PAFR transcript 2</rna> ( tissue-type ) , are upregulated by <protein>PAF</protein> as well as by 12-O-tetradecanoylphorbol-13-acetate ( TPA ) in the <cell_line>human stomach cancer cell line</cell_line> ( <cell_line>JR-St cells</cell_line> ) which expresses both functional <rna>PAFR transcript 1</rna> and <rna>PAFR transcript 2</rna> endogenously .


Functional analysis of the promoter 1 with a transient expression assay using chloramphenicol acetyltransferase ( CAT ) gene as a reporter showed that both PAF and TPA activated the promoter 1 but not the deleted promoter lacking the three consensus binding sites for NF-kappa B located from -571 bp to -459 bp .

Functional analysis of the <dna>promoter 1</dna> with a transient expression assay using <dna>chloramphenicol acetyltransferase ( CAT ) gene</dna> as a reporter showed that both <protein>PAF</protein> and TPA activated the <dna>promoter 1</dna> but not the deleted promoter lacking the three <dna>consensus binding sites</dna> for <protein>NF-kappa B</protein> located from -571 bp to -459 bp .


These findings suggest a molecular mechanism of positive regulation of PAFR gene expression by PAF through NF-kappa B , possibly by a phosphorylation reaction involving protein kinase C by PAF .

These findings suggest a molecular mechanism of positive regulation of <protein>PAFR</protein> gene expression by <protein>PAF</protein> through <protein>NF-kappa B</protein> , possibly by a phosphorylation reaction involving <protein>protein kinase C</protein> by <protein>PAF</protein> .


One gene , two transcripts : isolation of an alternative transcript encoding for the autoantigen La/SS-B from a cDNA library of a patient with primary Sjogrens ' syndrome .

One gene , two <rna>transcripts</rna> : isolation of an alternative transcript encoding for the <protein>autoantigen La/SS-B</protein> from a <dna>cDNA library</dna> of a patient with primary Sjogrens ' syndrome .


A cDNA library was prepared from peripheral blood lymphocytes of an autoimmune patient with primary Sjogrens ' syndrome .

A <dna>cDNA library</dna> was prepared from peripheral blood <cell_type>lymphocytes</cell_type> of an autoimmune patient with primary Sjogrens ' syndrome .


The cDNA library was screened with the patients own autoimmune serum being monospecific for the nuclear autoantigen La/SS-B .

The <dna>cDNA library</dna> was screened with the patients own autoimmune serum being monospecific for the <protein>nuclear autoantigen La/SS-B</protein> .


Thereby an alternative type of La mRNA was identified that differed from the known La mRNA due to an exchange of the exon 1 .

Thereby an alternative type of <rna>La mRNA</rna> was identified that differed from the known <rna>La mRNA</rna> due to an exchange of the <dna>exon 1</dna> .


Sequencing of the genomic region between the exons 1 and 2 showed that the alternative 5'-end is a part of the intron .

Sequencing of the genomic region between the <dna>exons 1 and 2</dna> showed that the <dna>alternative 5'-end</dna> is a part of the <dna>intron</dna> .


In addition , the presence of an alternative promoter site , which exists within the intron downstream of the exon 1 , became evident .

In addition , the presence of an <dna>alternative promoter site</dna> , which exists within the <dna>intron</dna> downstream of the <dna>exon 1</dna> , became evident .


In consequence , the alternative La mRNA is the result of a promoter switching combined with an alternative splicing mechanism .

In consequence , the <rna>alternative La mRNA</rna> is the result of a promoter switching combined with an alternative splicing mechanism .


In the intron , further transcription factor binding sites , including a NF-kappa B element , were identified leading to the suggestion that the expression of the gene encoding for the nuclear autoantigen La/SS-B alters in dependence on disease conditions .

In the intron , further <protein>transcription factor</protein> binding sites , including a <dna>NF-kappa B element</dna> , were identified leading to the suggestion that the expression of the gene encoding for the <protein>nuclear autoantigen La/SS-B</protein> alters in dependence on disease conditions .


Cross-linking CD40 on B cells rapidly activates nuclear factor-kappa B .

Cross-linking <protein>CD40</protein> on <cell_type>B cells</cell_type> rapidly activates <protein>nuclear factor-kappa B</protein> .


The B cell-associated surface molecule CD40 functions to regulate B cell responses .

The <protein>B cell-associated surface molecule CD40</protein> functions to regulate B cell responses .


Cross-linking CD40 on B cells can lead to homotypic cell adhesion , IL-6 production , and , in combination with cytokines , to Ig isotype switching .

Cross-linking <protein>CD40</protein> on <cell_type>B cells</cell_type> can lead to homotypic cell adhesion , <protein>IL-6</protein> production , and , in combination with <protein>cytokines</protein> , to Ig isotype switching .


Tyrosine kinase activity is increased shortly after engagement of this receptor .


Little is known about how the very early events induced by CD40 cross-linking link to cellular responses .

Little is known about how the very early events induced by <protein>CD40</protein> cross-linking link to cellular responses .


In this study , we demonstrate that nuclear factor ( NF ) -kappa B and NF-kappa B-like transcription factors are activated after cross-linking CD40 on resting human tonsillar B cells and on B cell lines .

In this study , we demonstrate that <protein>nuclear factor ( NF ) -kappa B</protein> and <protein>NF-kappa B-like transcription factors</protein> are activated after cross-linking <protein>CD40</protein> on resting <cell_type>human tonsillar B cells</cell_type> and on <cell_line>B cell lines</cell_line> .


The activation is rapid and is mediated through a tyrosine kinase-dependent pathway .


The complexes detected in electrophoretic mobility shift assays contain p50 , p65 ( RelA ) , c-Rel , and most likely other components .

The complexes detected in electrophoretic mobility shift assays contain <protein>p50</protein> , <protein>p65</protein> ( <protein>RelA</protein> ) , <protein>c-Rel</protein> , and most likely other components .


By using transient transfection assays , we found that cross-linking CD40 supports NF-kappa B -dependent gene expression .

By using transient transfection assays , we found that cross-linking <protein>CD40</protein> supports <protein>NF-kappa B</protein> -dependent gene expression .


Our results define the NF-kappa B system as an intermediate event in CD40 signaling and suggest that the CD40 pathway can influence the expression of B cell-associated genes with NF-kappa B consensus sites .

Our results define the <protein>NF-kappa B</protein> system as an intermediate event in <protein>CD40</protein> signaling and suggest that the <protein>CD40</protein> pathway can influence the expression of <dna>B cell-associated genes</dna> with <dna>NF-kappa B consensus sites</dna> .


Protease inhibitors block lipopolysaccharide induction of tissue factor gene expression in human monocytic cells by preventing activation of c-Rel/p65 heterodimers .

Protease inhibitors block lipopolysaccharide induction of tissue factor gene expression in <cell_type>human monocytic cells</cell_type> by preventing activation of <protein>c-Rel/p65 heterodimers</protein> .


Tissue factor ( TF ) is expressed rapidly by human monocytes exposed to bacterial endotoxin ( lipopolysaccharide , or LPS ) .

<protein>Tissue factor</protein> ( <protein>TF</protein> ) is expressed rapidly by <cell_type>human monocytes</cell_type> exposed to <protein>bacterial endotoxin</protein> ( lipopolysaccharide , or LPS ) .


Transcriptional regulation is mediated by binding of c-Rel/p65 heterodimers to a kappa B-like site in the TF promoter .

Transcriptional regulation is mediated by binding of <protein>c-Rel/p65 heterodimers</protein> to a <dna>kappa B-like site</dna> in the <dna>TF promoter</dna> .


Nuclear translocation of cytosolic c-Rel/p65 heterodimers and other members of the NF-kappa B/Rel family requires dissociation and proteolytic degradation of the inhibitor protein , I kappa B alpha .

Nuclear translocation of <protein>cytosolic c-Rel/p65 heterodimers</protein> and other members of the <protein>NF-kappa B/Rel family</protein> requires dissociation and proteolytic degradation of the <protein>inhibitor protein</protein> , <protein>I kappa B alpha</protein> .


The protease inhibitors N alpha-tosylphenylalanyl chloromethyl ketone ( TPCK ) and N alpha-tosyl-L-lysine chloromethyl ketone ( TLCK ) block activation of NF-kappa B/Rel proteins by preventing degradation of I kappa B alpha .

The protease inhibitors N alpha-tosylphenylalanyl chloromethyl ketone ( TPCK ) and N alpha-tosyl-L-lysine chloromethyl ketone ( TLCK ) block activation of <protein>NF-kappa B/Rel proteins</protein> by preventing degradation of <protein>I kappa B alpha</protein> .


To determine if TPCK and TLCK inhibited LPS induction of TF expression , freshly isolated human monocytes and monocytic THP-1 cells were pretreated with these inhibitors for 30 min before LPS stimulation .

To determine if TPCK and TLCK inhibited LPS induction of <protein>TF</protein> expression , freshly isolated <cell_type>human monocytes</cell_type> and <cell_line>monocytic THP-1 cells</cell_line> were pretreated with these inhibitors for 30 min before LPS stimulation .


Both TPCK and TLCK inhibited LPS induction of TF protein , TF mRNA and TF promoter activity in a dose-dependent manner .

Both TPCK and TLCK inhibited LPS induction of <protein>TF protein</protein> , <rna>TF mRNA</rna> and <protein>TF</protein> promoter activity in a dose-dependent manner .


These inhibitors specifically prevented degradation of I kappa B alpha and nuclear translocation of c-Rel/p65 heterodimers .

These inhibitors specifically prevented degradation of <protein>I kappa B alpha</protein> and nuclear translocation of <protein>c-Rel/p65 heterodimers</protein> .


In contrast , TPCK and TLCK did not block induction of an immediate-early gene encoding the transcription factor , Egr-1 .

In contrast , TPCK and TLCK did not block induction of an <dna>immediate-early gene</dna> encoding the <protein>transcription factor</protein> , <protein>Egr-1</protein> .


Taken together , these data indicated that inhibiting nuclear translocation of c-Rel/p65 heterodimers prevented LPS induction of TF gene transcription in monocytic cells .

Taken together , these data indicated that inhibiting nuclear translocation of <protein>c-Rel/p65 heterodimers</protein> prevented LPS induction of <protein>TF</protein> gene transcription in <cell_type>monocytic cells</cell_type> .


1 , 25-Dihydroxyvitamin D3 receptors in peripheral blood mononuclear cells from patients with primary and secondary hyperparathyroidism .

<protein>1 , 25-Dihydroxyvitamin D3 receptors</protein> in <cell_type>peripheral blood mononuclear cells</cell_type> from patients with primary and secondary hyperparathyroidism .


A decreased number of calcitriol ( 1 , 25 ( OH ) 2D3 ) receptors has been observed in parathyroid glands of uremic animals .

A decreased number of <protein>calcitriol ( 1 , 25 ( OH ) 2D3 ) receptors</protein> has been observed in parathyroid glands of uremic animals .


In humans , studies carried out in surgically removed parathyroid glands have shown that calcitriol binding is higher in primary than in secondary hyperparathyroidism .


Since specific receptors for calcitriol have been described in peripheral blood mononuclear cells ( PBMC ) , we have investigated the specific uptake of 3H-labelled 1 , 25 ( OH ) 2D3 in PBMC of 12 women with primary hyperparathyroidism ( PHP ) , 8 women with hyperparathyroidism secondary to chronic renal failure ( SH ) , 9 women with renal transplant ( RT ) , and 23 healthy women .

Since specific receptors for calcitriol have been described in <cell_type>peripheral blood mononuclear cells</cell_type> ( <cell_type>PBMC</cell_type> ) , we have investigated the specific uptake of 3H-labelled 1 , 25 ( OH ) 2D3 in <cell_type>PBMC</cell_type> of 12 women with primary hyperparathyroidism ( PHP ) , 8 women with hyperparathyroidism secondary to chronic renal failure ( SH ) , 9 women with renal transplant ( RT ) , and 23 healthy women .


The median dissociation constant ( Kd ) was similar in all three groups of patients and in healthy women ( mean +/- S.D. ( range ) : PHP , 1.2 +/- 1.0 ( 0.2-4 ) x 10 ( -10 ) M ; SH , 0.6 +/- 0.4 ( 0.2-1.2 ) x 10 ( -10 ) M ; RT , 1.1 +/- 0.5 ( 0.4-1.9 ) x 10 ( -10 ) M ; controls , 1.0 +/- 0.6 ( 0.3-2.6 ) x 10 ( -10 ) M ) . However , the maximal binding capacity ( Nmax ) was significantly enhanced in PHP ( 3.9 +/- 1.9 ( 1.3-7.6 ) fmol/10 ( 7 ) cells vs. 2.3 +/- 0.9 ( 1.1-4.4 ) fmol/10 ( 7 ) cells in controls ; P = 0.0006 ) and decreased in SH ( 0.8 +/- 0.5 ( 0.2-1.6 ) fmol/10 ( 7 ) cells vs. 2.3 +/- 0.9 ( 1.1-4.4 ) fmol/10 ( 7 ) cells in controls ; P = 0.0001 ) , whereas no changes were seen in RT ( 2.3 +/- 0.7 ( 1.2-3.3 ) fmol/10 ( 7 ) cells vs. 2.3 +/- 0.9 ( 1.1-4.4 ) fmol/10 ( 7 ) cells in controls ) .


In three patients with PHP who were subjected to parathyroidectomy , the calcitriol number came down to normal .


Changes of calcitriol receptors in primary and secondary hyperparathyroidism could magnify the consequences of disturbances in serum concentration of calcitriol itself and might play an important role in the development of secondary hyperparathyroidism in uremia .

Changes of <protein>calcitriol receptors</protein> in primary and secondary hyperparathyroidism could magnify the consequences of disturbances in serum concentration of calcitriol itself and might play an important role in the development of secondary hyperparathyroidism in uremia .


The severe phenotype of females with tiny ring X chromosomes is associated with inability of these chromosomes to undergo X inactivation .

The severe phenotype of females with <dna>tiny ring X chromosomes</dna> is associated with inability of these <dna>chromosomes</dna> to undergo X inactivation .


Mental retardation and a constellation of congenital malformations not usually associated with Turner syndrome are seen in some females with a mosaic 45 , X/46 , X , r ( X ) karyotype .


Studies of these females show that the XIST locus on their tiny ring X chromosomes is either not present or not expressed .

Studies of these females show that the <dna>XIST locus</dna> on their <dna>tiny ring X chromosomes</dna> is either not present or not expressed .


As XIST transcription is well correlated with inactivation of the X chromosome in female somatic cells and spermatogonia , nonexpression of the locus even when it is present suggests that these chromosomes are transcriptionally active .

As <dna>XIST</dna> transcription is well correlated with inactivation of the <dna>X chromosome</dna> in <cell_type>female somatic cells</cell_type> and <cell_type>spermatogonia</cell_type> , nonexpression of the locus even when it is present suggests that these <dna>chromosomes</dna> are transcriptionally active .


We examined the transcriptional activity of ring X chromosomes lacking XIST expression ( XISTE- ) , from three females with severe phenotypes .

We examined the transcriptional activity of ring <dna>X chromosomes</dna> lacking <dna>XIST</dna> expression ( XISTE- ) , from three females with severe phenotypes .


The two tiny ring X chromosomes studied with an antibody specific for the acetylated isoforms of histone H4 marking transcribed chromatin domains were labeled at a level consistent with their being active .

The two tiny ring <dna>X chromosomes</dna> studied with an <protein>antibody</protein> specific for the acetylated isoforms of <protein>histone H4</protein> marking <dna>transcribed chromatin domains</dna> were labeled at a level consistent with their being active .


We also examined tow of the XISTE- ring chromosomes to determine whether genes that are normally silent on an inactive X are expressed from these chromosomes .

We also examined tow of the <dna>XISTE- ring chromosomes</dna> to determine whether <dna>genes</dna> that are normally silent on an <dna>inactive X</dna> are expressed from these <dna>chromosomes</dna> .


Analyses of hybrid cells show that TIMP , ZXDA , and ZXDB loci on the proximal short arm , and AR and PHKA1 loci on the long arm , are well expressed from the tiny ring X chromosome lacking XIST DNA .

Analyses of <cell_line>hybrid cells</cell_line> show that <dna>TIMP</dna> , <dna>ZXDA</dna> , and <dna>ZXDB loci</dna> on the <dna>proximal short arm</dna> , and <dna>AR</dna> and <dna>PHKA1 loci</dna> on the long arm , are well expressed from the <dna>tiny ring X chromosome</dna> lacking <dna>XIST DNA</dna> .


Studies of the ring chromosome that has XIST DNA but does not transcribe it show that its AR allele is transcribed along with the one on the normal X allele .

Studies of the <dna>ring chromosome</dna> that has <dna>XIST DNA</dna> but does not transcribe it show that its AR allele is transcribed along with the one on the normal X allele .


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Inhibition of activation of transcription factor AP-1 by CD28 signalling in human T-cells .

Inhibition of activation of <protein>transcription factor AP-1</protein> by <protein>CD28</protein> signalling in <cell_type>human T-cells</cell_type> .


Co-stimulation of T-lymphocytes by T-cell receptor ( TcR ) occupancy and activation of the CD28 surface molecule results in enhanced proliferation and interleukin 2 ( IL-2 ) production .

Co-stimulation of <cell_type>T-lymphocytes</cell_type> by <protein>T-cell receptor</protein> ( <protein>TcR</protein> ) occupancy and activation of the <protein>CD28 surface molecule</protein> results in enhanced proliferation and <protein>interleukin 2</protein> ( <protein>IL-2</protein> ) production .


The increase in IL-2 gene expression triggered by CD28 involves a kappa B-like sequence in the 5'-regulatory region of the IL-2 promoter , called CD28-responsive element .

The increase in <protein>IL-2</protein> gene expression triggered by <protein>CD28</protein> involves a <dna>kappa B-like sequence</dna> in the <dna>5'-regulatory region</dna> of the <dna>IL-2 promoter</dna> , called <dna>CD28-responsive element</dna> .


Stimulation of T-cells by agonistic anti-CD28 antibodies in conjunction with phorbol 12-myristate 13-acetate ( PMA ) - or TcR -derived signals induces the enhanced activation of the transcription factor NF-kappa B .

Stimulation of <cell_type>T-cells</cell_type> by agonistic <protein>anti-CD28 antibodies</protein> in conjunction with phorbol 12-myristate 13-acetate ( PMA ) - or <protein>TcR</protein> -derived signals induces the enhanced activation of the <protein>transcription factor</protein> <protein>NF-kappa B</protein> .


Here we report that CD28 engagement , however , exerts opposite effects on the transcription factor AP-1 .

Here we report that <protein>CD28</protein> engagement , however , exerts opposite effects on the <protein>transcription factor AP-1</protein> .


Whereas anti-CD28 together with PMA increased the DNA binding and trans-activation activity of NF-kappa B , PMA-induced activation of AP-1 was significantly suppressed .

Whereas <protein>anti-CD28</protein> together with PMA increased the DNA binding and trans-activation activity of <protein>NF-kappa B</protein> , PMA-induced activation of <protein>AP-1</protein> was significantly suppressed .


The inhibitory effect exerted by anti-CD28 was observed at the level of DNA binding as well as in functional reporter-gene assays .

The inhibitory effect exerted by <protein>anti-CD28</protein> was observed at the level of DNA binding as well as in functional reporter-gene assays .


These results suggest that the two transcription factors are independently regulated and may perform different functions during T-cell activation .

These results suggest that the two <protein>transcription factors</protein> are independently regulated and may perform different functions during T-cell activation .


HIV-1 Nef leads to inhibition or activation of T cells depending on its intracellular localization .

<protein>HIV-1 Nef</protein> leads to inhibition or activation of <cell_type>T cells</cell_type> depending on its intracellular localization .


Nef of primate lentiviruses is required for viremia and progression to AIDS in monkeys .

<protein>Nef</protein> of primate lentiviruses is required for viremia and progression to AIDS in monkeys .


Negative , positive , and no effects of Nef have also been reported on viral replication in cells .

Negative , positive , and no effects of <protein>Nef</protein> have also been reported on viral replication in cells .


To reconcile these observations , we expressed a hybrid CD8-Nef protein in Jurkat cells .

To reconcile these observations , we expressed a <protein>hybrid CD8-Nef protein</protein> in <cell_line>Jurkat cells</cell_line> .


Two opposite phenotypes were found , which depended on the intracellular localization of Nef .

Two opposite phenotypes were found , which depended on the intracellular localization of <protein>Nef</protein> .


Expressed in the cytoplasm or on the cell surface , the chimera inhibited or activated early signaling events from the T cell antigen receptor .

Expressed in the cytoplasm or on the cell surface , the <protein>chimera</protein> inhibited or activated early signaling events from the <protein>T cell antigen receptor</protein> .


Activated Jurkat cells died by apoptosis , and only cells with mutated nef genes expressing truncated Nefs survived , which rendered Nef nonfunctional .

Activated <cell_line>Jurkat cells</cell_line> died by apoptosis , and only cells with mutated <dna>nef genes</dna> expressing truncated <protein>Nefs</protein> survived , which rendered <protein>Nef</protein> nonfunctional .


These mutations paralleled those in other viral strains passaged in vitro .


Not only do these positional effects of Nef reconcile diverse phenotypes of Nef and suggest a role for its N-terminal myristylation , but they also explain effects of Nef in HIV infection and progression to AIDS .

Not only do these positional effects of <protein>Nef</protein> reconcile diverse phenotypes of <protein>Nef</protein> and suggest a role for its N-terminal myristylation , but they also explain effects of <protein>Nef</protein> in HIV infection and progression to AIDS .


An intricate arrangement of binding sites for the Ets family of transcription factors regulates activity of the alpha 4 integrin gene promoter .

An intricate arrangement of binding sites for the <protein>Ets family</protein> of <protein>transcription factors</protein> regulates activity of the <dna>alpha 4 integrin gene promoter</dna> .


alpha 4 integrins mediate cell-cell and cell-extracellular matrix interactions that are critical for maturation and function of the immune system as well as differentiation of skeletal muscle .

<protein>alpha 4 integrins</protein> mediate cell-cell and cell-extracellular matrix interactions that are critical for maturation and function of the immune system as well as differentiation of skeletal muscle .


Here we examine molecular mechanisms controlling the pattern of alpha 4 expression .

Here we examine molecular mechanisms controlling the pattern of <protein>alpha 4</protein> expression .


The activity of constructs containing 5 ' deletion mutants of the alpha 4 gene promoter was compared in transfection assays into cell lines that express alpha 4 and cell lines that do not .

The activity of constructs containing <dna>5 ' deletion mutants</dna> of the <dna>alpha 4 gene promoter</dna> was compared in transfection assays into <cell_line>cell lines</cell_line> that express <protein>alpha 4</protein> and <cell_line>cell lines</cell_line> that do not .


The sequence between position -42 and -76 base pairs ( bp ) was required for efficient transcription in cells that express alpha 4 , but it showed no activity in HeLa cells , which do not express alpha 4 .

The sequence between position <dna>-42 and -76 base pairs</dna> ( bp ) was required for efficient transcription in cells that express <protein>alpha 4</protein> , but it showed no activity in <cell_line>HeLa cells</cell_line> , which do not express <protein>alpha 4</protein> .


Three binding sites for the Ets family of transcription factors are found in this region : two adjacent sites at positions -50 and -54 bp and a more 5 ' site at position -67 bp .

Three <dna>binding sites</dna> for the <protein>Ets family</protein> of <protein>transcription factors</protein> are found in this region : two adjacent sites at positions <dna>-50 and -54 bp</dna> and a more <dna>5 ' site</dna> at position <dna>-67 bp</dna> .


Using a series of constructs containing deletions and mutations in this region , we found that the 3'-most site alone was sufficient for binding GA-binding protein alpha ( GABP alpha ) /GABP beta and for a low level of transcriptional activation .

Using a series of constructs containing deletions and mutations in this region , we found that the <dna>3'-most site</dna> alone was sufficient for binding <protein>GA-binding protein alpha</protein> ( <protein>GABP alpha ) /GABP beta</protein> and for a low level of transcriptional activation .


When all three sites were present , a second complex `` a '' was detected , which contains an unknown member of the Ets family .

When all three sites were present , a second complex `` a '' was detected , which contains an unknown member of the <protein>Ets family</protein> .


Formation of complex a was cell-type specific and correlated with a high level of transcription .


Deletion of the 5'-most Ets site had no effect on binding to GABP alpha/GABP beta , but it eliminated a .

Deletion of the <dna>5'-most Ets site</dna> had no effect on binding to <protein>GABP alpha/GABP beta</protein> , but it eliminated a .


Concomitant with this loss of a , a new Ets-1-containing complex `` c `` appeared .

Concomitant with this loss of a , a <protein>new Ets-1-containing complex</protein> `` <protein>c</protein> `` appeared .


Complex c substituted efficiently for complex a in transcriptional activation .


We conclude that although neither of the two 5'-most Ets sites alone binds nuclear protein , they appear to act as modulators which control the pattern of Ets proteins that bind the alpha 4 gene promoter .

We conclude that although neither of the two <dna>5'-most Ets sites</dna> alone binds <protein>nuclear protein</protein> , they appear to act as modulators which control the pattern of <protein>Ets proteins</protein> that bind the <dna>alpha 4 gene promoter</dna> .


This arrangement of Ets sites , coupled with the tissue- and developmental-specific expression of Ets members , likely play a key role in defining the pattern of alpha 4 integrin .

This arrangement of <dna>Ets sites</dna> , coupled with the tissue- and developmental-specific expression of <protein>Ets members</protein> , likely play a key role in defining the pattern of <protein>alpha 4 integrin</protein> .


Mechanism of antiandrogen action : conformational changes of the receptor .


Androgen receptor mRNA was translated in vitro , and androgen- and antiandrogen-bound receptor complexes were studied using limited proteolytic digestion by trypsin .

<rna>Androgen receptor mRNA</rna> was translated in vitro , and <protein>androgen- and antiandrogen-bound receptor complexes</protein> were studied using limited proteolytic digestion by <protein>trypsin</protein> .


Partial proteolysis of androgen-bound receptor protein resulted in a 29-kDa proteolysis-resisting fragment , whereas antiandrogen binding stabilised a 35-kDa fragment .

Partial proteolysis of <protein>androgen-bound receptor protein</protein> resulted in a <protein>29-kDa proteolysis-resisting fragment</protein> , whereas antiandrogen binding stabilised a <protein>35-kDa fragment</protein> .


Both fragments contain the entire ligand binding domain , and the 35-kDa fragment extended into the hinge region of the receptor .

Both fragments contain the entire <protein>ligand binding domain</protein> , and the <protein>35-kDa fragment</protein> extended into the <protein>hinge region</protein> of the receptor .


Several antiandrogens show agonistic properties for a mutated androgen receptor ( LNCaP cell variant ) ; trypsin digestion of antiandrogen-bound mutated receptor also resulted in a 29-kDa fragment .

Several antiandrogens show agonistic properties for a <protein>mutated androgen receptor</protein> ( <cell_line>LNCaP cell variant</cell_line> ) ; <protein>trypsin</protein> digestion of <protein>antiandrogen-bound mutated receptor</protein> also resulted in a <protein>29-kDa fragment</protein> .


Our results point to an important difference between antiandrogens and antagonists of other steroid hormone receptors .

Our results point to an important difference between antiandrogens and antagonists of other <protein>steroid hormone receptors</protein> .


Antiandrogens result in protection of both the hinge region and C-terminus of the androgen receptor agonist proteolytic attack , whereas other studies showed that antiestrogens and antiprogestagens expose the C-terminal end of the ligand binding domain of their respective receptors to protease .

Antiandrogens result in protection of both the <protein>hinge region</protein> and <protein>C-terminus</protein> of the <protein>androgen receptor</protein> agonist proteolytic attack , whereas other studies showed that antiestrogens and antiprogestagens expose the <protein>C-terminal end</protein> of the <protein>ligand binding domain</protein> of their respective receptors to <protein>protease</protein> .


Differences in conformation of the hinge region distinguish androgen-bound from antiandrogen-bound receptor complexes , which represents an important feature of antiandrogen action .

Differences in conformation of the <protein>hinge region</protein> distinguish <protein>androgen-bound</protein> from <protein>antiandrogen-bound receptor complexes</protein> , which represents an important feature of antiandrogen action .


Activation of nuclear factor kappa B in human neuroblastoma cell lines .

Activation of <protein>nuclear factor kappa B</protein> in <cell_line>human neuroblastoma cell lines</cell_line> .


The nuclear factor kappa B ( NF-kappa B ) is a eukaryotic transcription factor .

The <protein>nuclear factor kappa B</protein> ( <protein>NF-kappa B</protein> ) is a eukaryotic <protein>transcription factor</protein> .


In B cells and macrophages it is constitutively present in cell nuclei , whereas in many other cell types , NF-kappa B translocates from cytosol to nucleus as a result of transduction by tumor necrosis factor alpha ( TNF alpha ) , phorbol ester , and other polyclonal signals .

In <cell_type>B cells</cell_type> and <cell_type>macrophages</cell_type> it is constitutively present in cell nuclei , whereas in many other cell types , <protein>NF-kappa B</protein> translocates from cytosol to nucleus as a result of transduction by <protein>tumor necrosis factor alpha</protein> ( <protein>TNF alpha</protein> ) , phorbol ester , and other polyclonal signals .


Using neuroblastoma cell lines as models , we have shown that in neural cells NF-kappa B was present in the cytosol and translocated into nuclei as a result of TNF alpha treatment .

Using <cell_line>neuroblastoma cell lines</cell_line> as models , we have shown that in <cell_type>neural cells</cell_type> <protein>NF-kappa B</protein> was present in the cytosol and translocated into nuclei as a result of <protein>TNF alpha</protein> treatment .


The TNF alpha -activated NF-kappa B was transcriptionally functional .

The <protein>TNF alpha</protein> -activated <protein>NF-kappa B</protein> was transcriptionally functional .


NF-kappa B activation by TNF alpha was not correlated with cell differentiation or proliferation .

<protein>NF-kappa B</protein> activation by <protein>TNF alpha</protein> was not correlated with cell differentiation or proliferation .


However , reagents such as nerve growth factor ( NGF ) and the phorbol ester phorbol 12-myristate 13-acetate ( PMA ) , which induce phenotypical differentiation of the SH-SY5Y neuroblastoma cell line , activated NF-kappa B , but only in that particular cell line .

However , reagents such as <protein>nerve growth factor</protein> ( <protein>NGF</protein> ) and the phorbol ester phorbol 12-myristate 13-acetate ( PMA ) , which induce phenotypical differentiation of the <cell_line>SH-SY5Y neuroblastoma cell line</cell_line> , activated <protein>NF-kappa B</protein> , but only in that particular <cell_line>cell line</cell_line> .


In a NGF-responsive rat pheochromocytoma cell line , PC12 , PMA activated NF-kappa B , whereas NGF did not .

In a <cell_line>NGF-responsive rat pheochromocytoma cell line</cell_line> , <cell_line>PC12</cell_line> , PMA activated <protein>NF-kappa B</protein> , whereas <protein>NGF</protein> did not .


In other neuroblastoma cell lines , such as SK-N-Be ( 2 ) , the lack of PMA induction of differentiation was correlated with the lack of NF-kappa B activation .

In other <cell_line>neuroblastoma cell lines</cell_line> , such as <cell_line>SK-N-Be ( 2 )</cell_line> , the lack of PMA induction of differentiation was correlated with the lack of <protein>NF-kappa B</protein> activation .


We found , moreover , that in SK-N-Be ( 2 ) cells protein kinase C ( PKC ) enzymatic activity was much lower compared with that in a control cell line and that the low PKC enzymatic activity was due to low PKC protein expression .

We found , moreover , that in <cell_line>SK-N-Be ( 2 ) cells</cell_line> <protein>protein kinase C</protein> ( <protein>PKC</protein> ) enzymatic activity was much lower compared with that in a <cell_line>control cell line</cell_line> and that the low <protein>PKC</protein> enzymatic activity was due to low <protein>PKC</protein> protein expression .


NF-kappa B was not activated by retinoic acid , which induced morphological differentiation of all the neuroblastoma cell lines used in the present study .

<protein>NF-kappa B</protein> was not activated by retinoic acid , which induced morphological differentiation of all the <cell_line>neuroblastoma cell lines</cell_line> used in the present study .


Thus , NF-kappa B activation was not required for neuroblastoma cell differentiation .

Thus , <protein>NF-kappa B</protein> activation was not required for <cell_type>neuroblastoma</cell_type> cell differentiation .


Furthermore , the results obtained with TNF alpha proved that NF-kappa B activation was not sufficient for induction of neuroblastoma differentiation .

Furthermore , the results obtained with <protein>TNF alpha</protein> proved that <protein>NF-kappa B</protein> activation was not sufficient for induction of <cell_type>neuroblastoma</cell_type> differentiation .


ERP , a new member of the ets transcription factor/oncoprotein family : cloning , characterization , and differential expression during B-lymphocyte development .

<protein>ERP</protein> , a new member of the <protein>ets transcription factor/oncoprotein family</protein> : cloning , characterization , and differential expression during B-lymphocyte development .


The ets gene family encodes a group of proteins which function as transcription factors under physiological conditions and , if aberrantly expressed , can cause cellular transformation .

The <dna>ets gene family</dna> encodes a group of proteins which function as <protein>transcription factors</protein> under physiological conditions and , if aberrantly expressed , can cause cellular transformation .


We have recently identified two regulatory elements in the murine immunoglobulin heavy-chain ( IgH ) enhancer , pi and microB , which exhibit striking similarity to binding sites for ets-related proteins .

We have recently identified two regulatory elements in the <dna>murine immunoglobulin heavy-chain ( IgH ) enhancer</dna> , <dna>pi</dna> and <dna>microB</dna> , which exhibit striking similarity to <dna>binding sites</dna> for <dna>ets-related proteins</dna> .


To identify ets-related transcriptional regulators expressed in pre-B lymphocytes that may interact with either the pi or the microB site , we have used a PCR approach with degenerate oligonucleotides encoding conserved sequences in all members of the ets family .

To identify <protein>ets-related transcriptional regulators</protein> expressed in <cell_type>pre-B lymphocytes</cell_type> that may interact with either the <dna>pi</dna> or the <dna>microB site</dna> , we have used a PCR approach with degenerate oligonucleotides encoding conserved sequences in all members of the <dna>ets family</dna> .


We have cloned the gene for a new ets-related transcription factor , ERP ( ets-related protein ) , from the murine pre-B cell line BASC 6C2 and from mouse lung tissue .

We have cloned the gene for a new <protein>ets-related transcription factor</protein> , <protein>ERP</protein> ( <protein>ets-related protein</protein> ) , from the <cell_line>murine pre-B cell line</cell_line> <cell_line>BASC 6C2</cell_line> and from mouse lung tissue .


The ERP protein contains a region of high homology with the ETS DNA-binding domain common to all members of the ets transcription factor/oncoprotein family .

The <protein>ERP</protein> protein contains a region of high homology with the ETS DNA-binding domain common to all members of the <protein>ets transcription factor/oncoprotein family</protein> .


Three additional smaller regions show homology to the ELK-1 and SAP-1 genes , a subgroup of the ets gene family that interacts with the serum response factor .

Three additional smaller regions show homology to the ELK-1 and <protein>SAP-1</protein> genes , a subgroup of the <dna>ets gene family</dna> that interacts with the <protein>serum response factor</protein> .


Full-length ERP expresses only negligible DNA-binding activity by itself .

Full-length <protein>ERP</protein> expresses only negligible DNA-binding activity by itself .


Removal of the carboxy terminus enables ERP to interact with a variety of ets-binding sites including the E74 site , the IgH enhancer pi site , and the lck promoter ets site , suggesting a carboxy-terminal negative regulatory domain .

Removal of the <protein>carboxy terminus</protein> enables <protein>ERP</protein> to interact with a variety of <dna>ets-binding sites</dna> including the <dna>E74 site</dna> , the <dna>IgH enhancer pi site</dna> , and the <dna>lck promoter ets site</dna> , suggesting a <protein>carboxy-terminal negative regulatory domain</protein> .


At least three ERP-related transcripts are expressed in a variety of tissues .

At least three <protein>ERP-related transcripts</protein> are expressed in a variety of tissues .


However , within the B-cell lineage , ERP is highly expressed primarily at early stages of B-lymphocyte development , and expression declines drastically upon B-cell maturation , correlating with the enhancer activity of the IgH pi site .

However , within the <cell_type>B-cell lineage</cell_type> , <protein>ERP</protein> is highly expressed primarily at early stages of <cell_type>B-lymphocyte</cell_type> development , and expression declines drastically upon B-cell maturation , correlating with the enhancer activity of the <dna>IgH pi site</dna> .


These data suggest that ERP might play a role in B-cell development and in IgH gene regulation .

These data suggest that <protein>ERP</protein> might play a role in <cell_type>B-cell</cell_type> development and in <dna>IgH gene</dna> regulation .


Gene for a tissue-specific transcriptional activator ( EBF or Olf-1 ) , expressed in early B lymphocytes , adipocytes , and olfactory neurons , is located on human chromosome 5 , band q34 , and proximal mouse chromosome 11 .

Gene for a <protein>tissue-specific transcriptional activator</protein> ( <protein>EBF</protein> or <protein>Olf-1</protein> ) , expressed in <cell_type>early B lymphocytes</cell_type> , <cell_type>adipocytes</cell_type> , and <cell_type>olfactory neurons</cell_type> , is located on <dna>human chromosome 5</dna> , <dna>band q34</dna> , and <dna>proximal mouse chromosome 11</dna> .


Murine B lymphocytes , adipocytes , and olfactory neurons contain a DNA-binding protein that participates in the regulation of genes encoding tissue-specific components of signal transduction .

<cell_type>Murine B lymphocytes</cell_type> , <cell_type>adipocytes</cell_type> , and <cell_type>olfactory neurons</cell_type> contain a <protein>DNA-binding protein</protein> that participates in the regulation of <dna>genes</dna> encoding tissue-specific components of signal transduction .


Purification and cloning of this protein , termed early B-cell factor ( EBF ) , from murine B lymphocytes and independent cloning of a protein , termed Olf-1 , from olfactory neuronal cells revealed virtual complete amino acid sequence identity between these proteins .

Purification and cloning of this protein , termed early <protein>B-cell factor</protein> ( <protein>EBF</protein> ) , from <cell_type>murine B lymphocytes</cell_type> and independent cloning of a protein , termed <protein>Olf-1</protein> , from <cell_type>olfactory neuronal cells</cell_type> revealed virtual complete amino acid sequence identity between these proteins .


As a first step towards identifying a human genetic disorder or mouse mutation for which EBF could be a candidate gene , we have chromosomally mapped the corresponding locus in both species .

As a first step towards identifying a human genetic disorder or mouse mutation for which <protein>EBF</protein> could be a candidate gene , we have chromosomally mapped the corresponding locus in both species .


By Southern hybridization analyses of somatic cell hybrid panels with murine cDNA probe , fluorescence chromosomal in situ hybridization ( FISH ) of human genomic clones , and analysis of recombinant inbred mouse strains , we have found single sites for EBF homologous sequences on human Chromosome ( Chr ) 5 , band q34 , and on proximal mouse Chr 11 , in an evolutionarily conserved region .

By Southern hybridization analyses of somatic cell hybrid panels with <dna>murine cDNA probe</dna> , fluorescence chromosomal in situ hybridization ( FISH ) of <dna>human genomic clones</dna> , and analysis of <cell_line>recombinant inbred mouse strains</cell_line> , we have found single sites for <dna>EBF homologous sequences</dna> on human Chromosome ( Chr ) 5 , <dna>band q34</dna> , and on <dna>proximal mouse Chr 11</dna> , in an <dna>evolutionarily conserved region</dna> .


Calcineurin activates transcription from the GM-CSF promoter in synergy with either protein kinase C or NF-kappa B /AP-1 in T cells .

<protein>Calcineurin</protein> activates transcription from the <dna>GM-CSF promoter</dna> in synergy with either <protein>protein kinase C</protein> or <protein>NF-kappa B</protein> <protein>/AP-1</protein> in <cell_type>T cells</cell_type> .


Two cis-acting elements GM-kappa B/GC-box and CLE0 , of the granulocyte-macrophage colony-stimulating factor ( GM-CSF ) gene are required for maximal induction in Jurkat T cells by costimulation with phorbol-12-myristate acetate ( PMA ) and Ca2+ ionophore ( A23187 ) .

Two <dna>cis-acting elements</dna> <dna>GM-kappa B/GC-box</dna> and <dna>CLE0</dna> , of the <dna>granulocyte-macrophage colony-stimulating factor ( GM-CSF ) gene</dna> are required for maximal induction in <cell_line>Jurkat T cells</cell_line> by costimulation with phorbol-12-myristate acetate ( PMA ) and Ca2+ ionophore ( A23187 ) .


The GM-kappa B sequence is recognized by NF-kappa B , which is mainly induced by PMA .

The <dna>GM-kappa B sequence</dna> is recognized by <protein>NF-kappa B</protein> , which is mainly induced by PMA .


The CLE0 sequence interacts with factors , related to a PMA-induced AP-1 and a PMA/A23187-induced NF-AT .

The <dna>CLE0 sequence</dna> interacts with factors , related to a <protein>PMA-induced AP-1</protein> and a <protein>PMA/A23187-induced NF-AT</protein> .


We examined whether signal transducing components in T cells can activate transcription of the GM-CSF gene .

We examined whether signal transducing components in <cell_type>T cells</cell_type> can activate transcription of the <dna>GM-CSF gene</dna> .


Cotransfection of NF-kappa B ( p50/p65 ) - or AP-1 ( c-Jun/c-Fos ) - expression vectors into Jurkat cells with a luciferase reporter containing the GM-CSF promoter did not stimulate transcription from the GM-CSF promoter .

Cotransfection of <dna>NF-kappa B ( p50/p65 ) - or AP-1 ( c-Jun/c-Fos ) - expression vectors</dna> into <cell_line>Jurkat cells</cell_line> with a <dna>luciferase reporter</dna> containing the <dna>GM-CSF promoter</dna> did not stimulate transcription from the <dna>GM-CSF promoter</dna> .


In contrast , cotransfection with a combination of NF-kappa B and AP-1 significantly augmented transcription from the GM-CSF promoter containing the GM-kappa B/GC-box and the CLE0 ( AP-1/NF-AT ) .

In contrast , cotransfection with a combination of <protein>NF-kappa B</protein> and <protein>AP-1</protein> significantly augmented transcription from the <dna>GM-CSF promoter</dna> containing the <dna>GM-kappa B/GC-box</dna> and the <dna>CLE0</dna> ( <protein>AP-1/NF-AT</protein> ) .


Expression of a constitutively active calcineurin ( CN ) , a Ca2+/calmodulin-dependent protein phosphatase , potentiated by two fold the transcriptional activation by NF-kappa B /AP-1 .

Expression of a constitutively active <protein>calcineurin</protein> ( <protein>CN</protein> ) , a <protein>Ca2+/calmodulin-dependent protein phosphatase</protein> , potentiated by two fold the transcriptional activation by <protein>NF-kappa B</protein> <protein>/AP-1</protein> .


Both constitutively active forms of CN and protein kinase C ( PKC ) synergistically activated transcription from the GM-CSF promoter .

Both constitutively active forms of <protein>CN</protein> and <protein>protein kinase C</protein> ( <protein>PKC</protein> ) synergistically activated transcription from the <dna>GM-CSF promoter</dna> .


These results suggest that cooperation among NF-kappa B- , AP-1- and NF-AT-binding sequences is required for induction of the GM-CSF gene through PKC- and Ca2+- signaling pathways downstream of T cell activation .

These results suggest that cooperation among <dna>NF-kappa B- , AP-1- and NF-AT-binding sequences</dna> is required for induction of the <dna>GM-CSF gene</dna> through PKC- and Ca2+- signaling pathways downstream of T cell activation .


Nonpituitary human prolactin gene transcription is independent of Pit-1 and differentially controlled in lymphocytes and in endometrial stroma .

<dna>Nonpituitary human prolactin gene</dna> transcription is independent of <protein>Pit-1</protein> and differentially controlled in <cell_type>lymphocytes</cell_type> and in endometrial stroma .


Expression of the human PRL ( hPRL ) gene in extrapituitary sites such as the uterus ( decidualized endometrial stroma and myometrium ) and cells of the hematopoietic lineage is directed by an alternative promoter which is located approximately 6 kilobases ( kb ) upstream of the pituitary-specific start site .

Expression of the <dna>human PRL ( hPRL ) gene</dna> in extrapituitary sites such as the uterus ( decidualized endometrial stroma and myometrium ) and cells of the <cell_type>hematopoietic lineage</cell_type> is directed by an <dna>alternative promoter</dna> which is located approximately <dna>6 kilobases ( kb ) upstream</dna> of the <dna>pituitary-specific start site</dna> .


In order to delineate the tissue-specific mechanisms governing the control of nonpituitary PRL gene expression , we have cloned and sequenced 3 kb 5'-flanking DNA of the upstream decidual/lymphoid ( dPRL ) promoter .

In order to delineate the tissue-specific mechanisms governing the control of nonpituitary <dna>PRL gene</dna> expression , we have cloned and sequenced <dna>3 kb 5'-flanking DNA</dna> of the upstream <dna>decidual/lymphoid ( dPRL ) promoter</dna> .


Based on sequence homology we identified two binding motifs for Pit-1 and seven half-sites for glucocorticoid receptor/progesterone receptor ( PR ) binding .

Based on sequence homology we identified two <dna>binding motifs</dna> for <protein>Pit-1</protein> and seven <dna>half-sites</dna> for <protein>glucocorticoid receptor/progesterone receptor</protein> ( <protein>PR</protein> ) binding .


We focused our studies on the role of Pit-1 and of PR as potential transcriptional regulators , since the POU domain protein Pit-1 is essential in the control of pituitary PRL expression , and progesterone induces decidual transformation of the endometrial stroma , a differentiation process during which the decidual PRL gene is activated .

We focused our studies on the role of <protein>Pit-1</protein> and of <protein>PR</protein> as potential <protein>transcriptional regulators</protein> , since the <protein>POU domain protein</protein> <protein>Pit-1</protein> is essential in the control of pituitary <protein>PRL</protein> expression , and progesterone induces decidual transformation of the endometrial stroma , a differentiation process during which the decidual <dna>PRL gene</dna> is activated .


We demonstrate in a variety of cell types , including lymphocytes and endometrial stroma , that Pit-1 is not involved in the regulation of dPRL promoter/reporter gene constructs carrying 3 kb 5'-flanking DNA .

We demonstrate in a variety of cell types , including <cell_type>lymphocytes</cell_type> and endometrial stroma , that <protein>Pit-1</protein> is not involved in the regulation of <dna>dPRL promoter/reporter gene constructs</dna> carrying <dna>3 kb 5'-flanking DNA</dna> .


Our experiments also show that activated PR does not confer direct transcriptional control on the dPRL promoter .

Our experiments also show that activated <protein>PR</protein> does not confer direct transcriptional control on the <dna>dPRL promoter</dna> .


When we compared the activity of the transfected dPRL promoter in PRL-secreting and nonsecreting lymphoid cells , we found that the 3 kb 5'-flanking region of the dPRL promoter did not contain elements restricting expression to only those lymphocytes that produce PRL but allowed expression of fusion reporter genes irrespective of the status of the endogenous PRL gene .

When we compared the activity of the transfected <dna>dPRL promoter</dna> in <cell_type>PRL-secreting and nonsecreting lymphoid cells</cell_type> , we found that the <dna>3 kb 5'-flanking region</dna> of the <dna>dPRL promoter</dna> did not contain elements restricting expression to only those <cell_type>lymphocytes</cell_type> that produce PRL but allowed expression of fusion reporter genes irrespective of the status of the endogenous <dna>PRL gene</dna> .


This was in sharp contrast to endometrial cells where 3 kb 5'-flanking DNA conferred strong transcriptional activation on the dPRL promoter in decidualized endometrial stromal cells actively secreting PRL , but did not allow transcription in undifferentiated non-PRL-secreting endometrial stromal cells .

This was in sharp contrast to endometrial cells where 3 kb 5'-flanking DNA conferred strong transcriptional activation on the <dna>dPRL promoter</dna> in decidualized <cell_type>endometrial stromal cells</cell_type> actively secreting <protein>PRL</protein> , but did not allow transcription in undifferentiated <cell_type>non-PRL-secreting endometrial stromal cells</cell_type> .


Activation of the dPRL promoter construct in these undifferentiated cells could however be induced by the addition of cAMP , in the absence of progesterone , suggesting that a signal transduced through the cAMP signaling pathway is a primary inducer of decidual PRL gene expression .

Activation of the <dna>dPRL promoter</dna> construct in these undifferentiated cells could however be induced by the addition of cAMP , in the absence of progesterone , suggesting that a signal transduced through the cAMP signaling pathway is a primary inducer of decidual <dna>PRL gene</dna> expression .


Signals and nuclear factors that regulate the expression of interleukin-4 and interleukin-5 genes in helper T cells .

Signals and <protein>nuclear factors</protein> that regulate the expression of <dna>interleukin-4 and interleukin-5 genes</dna> in <cell_type>helper T cells</cell_type> .


Mouse thymoma line EL-4 cells produce cytokines such as interleukin ( IL ) -2 , IL-3 , IL-4 , IL-10 , and granulocyte-macrophage colony-stimulating factor in response to phorbol 12-myristate 13-acetate ( PMA ) .

<cell_line>Mouse thymoma line EL-4 cells</cell_line> produce <protein>cytokines</protein> such as <protein>interleukin ( IL ) -2</protein> , <protein>IL-3</protein> , <protein>IL-4</protein> , <protein>IL-10</protein> , and <protein>granulocyte-macrophage colony-stimulating factor</protein> in response to phorbol 12-myristate 13-acetate ( PMA ) .


EL-4 cells also produce low levels of IL-5 when stimulated by PMA alone ; however , cAMP greatly augments PMA-dependent IL-5 production .

<cell_line>EL-4 cells</cell_line> also produce low levels of <protein>IL-5</protein> when stimulated by PMA alone ; however , cAMP greatly augments PMA-dependent <protein>IL-5</protein> production .


A transient transfection assay revealed that two signals , PMA and cAMP , are required for optimal activation of the IL-5 promoter .

A transient transfection assay revealed that two signals , PMA and cAMP , are required for optimal activation of the <dna>IL-5 promoter</dna> .


In contrast , cAMP almost completely inhibited the PMA-dependent activation of the endogenous IL-2 gene , as well as the transfected IL-2 promoter .

In contrast , cAMP almost completely inhibited the PMA-dependent activation of the <dna>endogenous IL-2 gene</dna> , as well as the transfected <dna>IL-2 promoter</dna> .


These results indicate that the IL-5 gene is positively regulated by cAMP in a manner opposite to that for the IL-2 gene .

These results indicate that the <dna>IL-5 gene</dna> is positively regulated by cAMP in a manner opposite to that for the <dna>IL-2 gene</dna> .


One of the nuclear factors ( NFs ) that regulates the response of the IL-5 promoter to cAMP and PMA has properties similar to NF for activated t cell .

One of the <protein>nuclear factors</protein> ( <protein>NFs</protein> ) that regulates the response of the <dna>IL-5 promoter</dna> to cAMP and PMA has properties similar to <protein>NF</protein> for <cell_type>activated t cell</cell_type> .


The P sequence of the IL-4 gene , defined as a responsive element for PMA and calcium ionophore ( A23187 ) , shares sequence similarity with the NF kappa B and the NF-activated T cell binding sites .

The <dna>P sequence</dna> of the <dna>IL-4 gene</dna> , defined as a <dna>responsive element</dna> for PMA and calcium ionophore ( A23187 ) , shares sequence similarity with the <dna>NF kappa B and the NF-activated T cell binding sites</dna> .


We attempted to determine whether NF ( P ) , a nuclear factor specific for the P sequence , is related to NF-kappa B and nuclear factor for activated T cell ( NF-AT ) .

We attempted to determine whether <protein>NF ( P )</protein> , a nuclear factor specific for the <dna>P sequence</dna> , is related to <protein>NF-kappa B</protein> and <protein>nuclear factor for activated T cell</protein> ( <protein>NF-AT</protein> ) .


In electromobility shift assays both NF-kappa B ( P65 or P65/P50 heterodimer ) and NF-AT bound to the P sequence .

In electromobility shift assays both <protein>NF-kappa B</protein> ( <protein>P65</protein> or <protein>P65/P50 heterodimer</protein> ) and <protein>NF-AT</protein> bound to the <dna>P sequence</dna> .


However , sequence specificity of NF-AT was more similar to that of NF ( P ) , and only a small amount of P65 was detected in NF ( P ) .

However , sequence specificity of <protein>NF-AT</protein> was more similar to that of <protein>NF ( P )</protein> , and only a small amount of <protein>P65</protein> was detected in <protein>NF ( P )</protein> .


These results indicate that a component or components of NF-AT have the potential to reconstitute NF ( P ) , whereas NF-kappa B alone does not account for NF ( P ) in Jurkat crude extract .

These results indicate that a component or components of <protein>NF-AT</protein> have the potential to reconstitute <protein>NF ( P )</protein> , whereas <protein>NF-kappa B</protein> alone does not account for <protein>NF ( P )</protein> in Jurkat crude extract .


Taken together , these results suggest that NF-AT-like factors are involved in the regulation of IL-4 and IL-5 genes .

Taken together , these results suggest that <protein>NF-AT-like factors</protein> are involved in the regulation of <dna>IL-4 and IL-5 genes</dna> .


Solution structure of a POU-specific homeodomain : 3D-NMR studies of human B-cell transcription factor Oct-2 .

Solution structure of a <protein>POU-specific homeodomain</protein> : 3D-NMR studies of human <protein>B-cell transcription factor</protein> <protein>Oct-2</protein> .


The POU DNA-binding motif defines a conserved family of eukaryotic transcription factors involved in regulation of gene expression .

The <protein>POU DNA-binding motif</protein> defines a conserved family of <protein>eukaryotic transcription factors</protein> involved in regulation of gene expression .


This bipartite motif consists of an N-terminal POU-specific domain ( POUs ) , a flexible linker , and a C-terminal POU-specific homeodomain ( POUHD ) .

This <protein>bipartite motif</protein> consists of an <protein>N-terminal POU-specific domain</protein> ( <protein>POUs</protein> ) , a <protein>flexible linker</protein> , and a <protein>C-terminal POU-specific homeodomain</protein> ( <protein>POUHD</protein> ) .


Here we describe the solution structure of a POU-specific homeodomain .

Here we describe the solution structure of a <protein>POU-specific homeodomain</protein> .


An NMR model is obtained from Oct-2 , a human B-cell specific transcription factor which participates in the regulation of immunoglobulin genes .

An NMR model is obtained from <protein>Oct-2</protein> , a <protein>human B-cell specific transcription factor</protein> which participates in the regulation of <dna>immunoglobulin genes</dna> .


A fragment of Oct-2 containing POUHD and an adjoining linker was expressed in Escherichia coli and characterized by three-dimensional nuclear magnetic resonance ( 3D-NMR ) spectroscopy .

A fragment of <protein>Oct-2</protein> containing <protein>POUHD</protein> and an adjoining linker was expressed in Escherichia coli and characterized by three-dimensional nuclear magnetic resonance ( 3D-NMR ) spectroscopy .


Complete 1H and 15N resonance assignment of the POUHD moiety is presented .

Complete 1H and 15N resonance assignment of the <protein>POUHD moiety</protein> is presented .


The POUHD solution structure , as calculated by distance geometry and simulated annealing ( DG/SA ) , is similar to that of canonical homeodomains .

The <protein>POUHD</protein> solution structure , as calculated by distance geometry and simulated annealing ( DG/SA ) , is similar to that of <protein>canonical homeodomains</protein> .


A salient difference between solution and crystal structures is observed in the C-terminal segment of alpha-helix 3 ( the HTH recognition helix ) , which is not well ordered in solution .

A salient difference between solution and crystal structures is observed in the <protein>C-terminal segment</protein> of <protein>alpha-helix 3</protein> ( the <protein>HTH recognition helix</protein> ) , which is not well ordered in solution .


Because this segment presumably folds upon specific DNA binding , its flexibility in solution may reduce the intrinsic DNA affinity of POUHD in the absence of POUs .

Because this segment presumably folds upon specific DNA binding , its flexibility in solution may reduce the intrinsic DNA affinity of <protein>POUHD</protein> in the absence of <protein>POUs</protein> .


NF-kappa B-dependent and -independent pathways of HIV activation in a chronically infected T cell line .

NF-kappa B-dependent and -independent pathways of HIV activation in a <cell_line>chronically infected T cell line</cell_line> .


J delta K cells were isolated as a chronically infected survivor cell line , following infection of Jurkat CD4+ T cells with dl-NF , a mutated strain of human immunodeficiency virus type 1 ( HIV-1 ) containing a deletion of the long terminal repeat ( LTR ) NF-kappa B sites .

<cell_line>J delta K cells</cell_line> were isolated as a <cell_line>chronically infected survivor cell line</cell_line> , following infection of <cell_line>Jurkat CD4+ T cells</cell_line> with dl-NF , a mutated strain of human immunodeficiency virus type 1 ( HIV-1 ) containing a deletion of the <dna>long terminal repeat</dna> ( <dna>LTR</dna> ) <protein>NF-kappa B</protein> sites .


J delta K cells exhibited very low levels of constitutive HIV production .

<cell_line>J delta K cells</cell_line> exhibited very low levels of constitutive HIV production .


HIV-1 expression was activated from J delta K cells by treatment with phorbol myristate acetate ( PMA ) , sodium butyrate ( NaB ) , or hexamethylene bisacetamide ( HMBA ) , but not tumor necrosis factor alpha ( TNF-alpha ) , confirming the role of NF-kappa B in mediating TNF-alpha induction of HIV transcription .

HIV-1 expression was activated from <cell_line>J delta K cells</cell_line> by treatment with phorbol myristate acetate ( PMA ) , sodium butyrate ( NaB ) , or hexamethylene bisacetamide ( HMBA ) , but not <protein>tumor necrosis factor alpha</protein> ( <protein>TNF-alpha</protein> ) , confirming the role of <protein>NF-kappa B</protein> in mediating <protein>TNF-alpha</protein> induction of HIV transcription .


The strong induction of HIV expression by NaB or HMBA in J delta K cells clearly demonstrates the existence of NF-kappa B -independent mechanisms of HIV activation in chronically infected cells .

The strong induction of HIV expression by NaB or HMBA in <cell_line>J delta K cells</cell_line> clearly demonstrates the existence of <protein>NF-kappa B</protein> -independent mechanisms of HIV activation in <cell_type>chronically infected cells</cell_type> .


J delta K cells may provide a useful model for characterizing NF-kappa B -independent transcriptional activation of the HIV LTR .

<cell_line>J delta K cells</cell_line> may provide a useful model for characterizing <protein>NF-kappa B</protein> -independent transcriptional activation of the <dna>HIV LTR</dna> .


JNK is involved in signal integration during costimulation of T lymphocytes .

<protein>JNK</protein> is involved in signal integration during costimulation of <cell_type>T lymphocytes</cell_type> .


T lymphocyte activation and interleukin-2 ( IL-2 ) production require at least two signals , generated by phorbol ester ( TPA ) and Ca2+ ionophore or costimulation of the T cell receptor ( TCR ) and the CD28 auxiliary receptor .

<cell_type>T lymphocyte</cell_type> activation and <protein>interleukin-2</protein> ( <protein>IL-2</protein> ) production require at least two signals , generated by phorbol ester ( TPA ) and Ca2+ ionophore or costimulation of the <protein>T cell receptor</protein> ( <protein>TCR</protein> ) and the <protein>CD28 auxiliary receptor</protein> .


We investigated how these stimuli affect mitogen activated protein ( MAP ) kinases .

We investigated how these stimuli affect <protein>mitogen activated protein ( MAP ) kinases</protein> .


Full activation of the MAP kinases that phosphorylate the Jun activation domain , JNK1 and JNK2 , required costimulation of T cells with either TPA and Ca2+ ionophore or antibodies to TCR and CD28 .

Full activation of the <protein>MAP kinases</protein> that phosphorylate the <protein>Jun activation domain</protein> , <protein>JNK1</protein> and <protein>JNK2</protein> , required costimulation of <cell_type>T cells</cell_type> with either TPA and Ca2+ ionophore or antibodies to <protein>TCR</protein> and <protein>CD28</protein> .


Alone , each stimulus resulted in little or no activation .


Similar to its effect on IL-2 induction , cyclosporin A ( CsA ) inhibited the synergistic activation of JNK , and a competitive inhibitor of Jun phosphorylation by JNK inhibited IL-2 promoter activation .

Similar to its effect on <protein>IL-2</protein> induction , cyclosporin A ( CsA ) inhibited the synergistic activation of <protein>JNK</protein> , and a competitive inhibitor of <protein>Jun</protein> phosphorylation by <protein>JNK</protein> inhibited <dna>IL-2 promoter</dna> activation .


By contrast , the MAP kinases ERK1 and ERK2 were fully activated by TPA or TCR stimulation and were not affected by Ca2+ , CD28 , or CsA .

By contrast , the <protein>MAP kinases</protein> <protein>ERK1</protein> and <protein>ERK2</protein> were fully activated by TPA or <protein>TCR</protein> stimulation and were not affected by Ca2+ , CD28 , or CsA .


Hence , integration of signals that lead to T cell activation occurs at the level of JNK activation .

Hence , integration of signals that lead to T cell activation occurs at the level of <protein>JNK</protein> activation .


Inhibition of rat splenocyte proliferation with methylprednisolone : in vivo effect of liposomal formulation .

Inhibition of <cell_type>rat splenocyte</cell_type> proliferation with methylprednisolone : in vivo effect of liposomal formulation .


The effect of a liposomal formulation of methylprednisolone ( MPL ) on the inhibition of lymphocyte proliferation in spleen cells was investigated following IV dosing in rats .

The effect of a liposomal formulation of methylprednisolone ( MPL ) on the inhibition of lymphocyte proliferation in <cell_type>spleen cells</cell_type> was investigated following IV dosing in rats .


Liposomes do not alter the suppressive action of MPL when placed in lymphocyte culture .

Liposomes do not alter the suppressive action of MPL when placed in <cell_line>lymphocyte culture</cell_line> .


Rat splenocytes were found to have greater sensitivity to MPL ( EC50 = 7.9 nM ) than do human peripheral blood lymphocytes ( EC50 = 28 nM ) .

<cell_type>Rat splenocytes</cell_type> were found to have greater sensitivity to MPL ( EC50 = 7.9 nM ) than do <cell_type>human peripheral blood lymphocytes</cell_type> ( EC50 = 28 nM ) .


In vivo studies in rats utilized 2 mg/kg IV bolus doses of liposomal MPL compared to drug in solution .


Animals were sacrificed at various times post-dosing until 120 h , spleen was excised and , after incubation of lymphocytes with PHA , splenocyte blastogenic responses were assessed by measuring cellular incorporation of 3H-thymidine .

Animals were sacrificed at various times post-dosing until 120 h , spleen was excised and , after incubation of <cell_type>lymphocytes</cell_type> with <protein>PHA</protein> , splenocyte blastogenic responses were assessed by measuring cellular incorporation of 3H-thymidine .


The suppressive effect of liposomal MPL in comparison with free drug was significantly prolonged ( > 120 h vs < 18 h ) .


Inhibition effects versus time were described by a pharmacodynamic model using MPL concentrations in plasma as an input function .

Inhibition effects versus time were described by a pharmacodynamic model using MPL concentrations in <cell_type>plasma</cell_type> as an input function .


A nonlinear relationship was found between suppression of splenocyte proliferation and the concentration of bound glucocorticoid receptors in spleen .

A nonlinear relationship was found between suppression of <cell_type>splenocyte</cell_type> proliferation and the concentration of bound <protein>glucocorticoid receptors</protein> in spleen .


Only partial receptor occupancy accompanied complete lymphocyte suppression .


The suppression of endogenous corticosterone in plasma for both treatments was similar with values from L-MPL rats returning to baseline after 24 h .

The suppression of endogenous corticosterone in <cell_type>plasma</cell_type> for both treatments was similar with values from L-MPL rats returning to baseline after 24 h .


These results demonstrate enhanced efficacy of local immunosuppression by targeting spleen with liposomal MPL .


Function of NF-kappa B/Rel binding sites in the major histocompatibility complex class II invariant chain promoter is dependent on cell-specific binding of different NF-kappa B/Rel subunits .

Function of <dna>NF-kappa B/Rel binding sites</dna> in the <dna>major histocompatibility complex class II invariant chain promoter</dna> is dependent on cell-specific binding of different <protein>NF-kappa B/Rel subunits</protein> .


The promoter of the human major histocompatibility complex class II-associated invariant-chain gene ( Ii ) contains two NF-kappa B/Rel binding sites located at -109 to -118 ( Ii kappa B-1 ) and -163 to -172 ( Ii kappa B-2 ) from the transcription start site .

The <dna>promoter</dna> of the human major <dna>histocompatibility complex class II-associated invariant-chain gene</dna> ( <dna>Ii</dna> ) contains two <dna>NF-kappa B/Rel binding sites</dna> located at <dna>-109 to -118</dna> ( <dna>Ii kappa B-1</dna> ) and <dna>-163 to -172</dna> ( <dna>Ii kappa B-2</dna> ) from the transcription start site .


We report here that the differential function of each of these NF-kappa B/Rel sites in several distinct cell types depends on cell-specific binding of NF-kappa B/Rel transcription factors .

We report here that the differential function of each of these <dna>NF-kappa B/Rel sites</dna> in several distinct cell types depends on cell-specific binding of <protein>NF-kappa B/Rel transcription factors</protein> .


Ii kappa B-1 is a positive regulatory element in B-cell lines and in the Ii-expressing T-cell line , H9 , but acts as a negative regulatory element in myelomonocytic and glia cell lines .

<dna>Ii kappa B-1</dna> is a <dna>positive regulatory element</dna> in <cell_line>B-cell lines</cell_line> and in the <cell_line>Ii-expressing T-cell line</cell_line> , <cell_line>H9</cell_line> , but acts as a <dna>negative regulatory element</dna> in <cell_line>myelomonocytic and glia cell lines</cell_line> .


In vivo protein-DNA contacts are detectable at Ii kappa B-1 in cell lines in which this site is functional as either a positive or negative regulator .

In vivo protein-DNA contacts are detectable at <dna>Ii kappa B-1</dna> in <cell_line>cell lines</cell_line> in which this site is functional as either a <dna>positive or negative regulator</dna> .


Electrophoretic mobility supershift assays determine that members of the NF-kappa B/Rel family of transcription factors can bind to this site in vitro and that DNA-binding complexes that contain p50 , p52 , p65 , and cRel correlate with positive regulation whereas the presence of p50 correlates with negative regulation .

Electrophoretic mobility supershift assays determine that members of the <protein>NF-kappa B/Rel family</protein> of <protein>transcription factors</protein> can bind to this site in vitro and that <protein>DNA-binding complexes</protein> that contain <protein>p50</protein> , <protein>p52</protein> , <protein>p65</protein> , and <protein>cRel</protein> correlate with positive regulation whereas the presence of <protein>p50</protein> correlates with negative regulation .


Ii kappa B-2 is a site of positive regulation in B-cell lines and a site of negative regulation in H9 T cells , myelomonocytic , and glial cell lines .

<dna>Ii kappa B-2</dna> is a site of positive regulation in <cell_line>B-cell lines</cell_line> and a site of negative regulation in <cell_line>H9 T cells</cell_line> , <cell_line>myelomonocytic , and glial cell lines</cell_line> .


In vivo occupancy of this site is observed only in the H9 T-cell line .

In vivo occupancy of this site is observed only in the <cell_line>H9 T-cell line</cell_line> .


Again , in vitro supershift studies indicate that the presence of p50 , p52 , p65 , and cRel correlates with positive function whereas the presence of only p50 and p52 correlates with negative function .

Again , in vitro supershift studies indicate that the presence of <protein>p50</protein> , <protein>p52</protein> , <protein>p65</protein> , and <protein>cRel</protein> correlates with positive function whereas the presence of only <protein>p50</protein> and <protein>p52</protein> correlates with negative function .


This differential binding of specific NF-kappa B/Rel subunits is likely to mediate the disparate functions of these two NF-kappa B/Rel binding sites .

This differential binding of specific <protein>NF-kappa B/Rel subunits</protein> is likely to mediate the disparate functions of these two <dna>NF-kappa B/Rel binding sites</dna> .


Epstein-Barr virus ( EBV ) replicative gene expression in tumour cells of AIDS-related non-Hodgkin 's lymphoma in relation to CD4 cell number and antibody titres to EBV .

Epstein-Barr virus ( EBV ) replicative gene expression in <cell_type>tumour cells</cell_type> of AIDS-related non-Hodgkin 's lymphoma in relation to <protein>CD4</protein> cell number and antibody titres to EBV .


OBJECTIVE : To determine whether activation of Epstein-Barr virus ( EBV ) replication in tumour cells of AIDS-related non-Hodgkin 's lymphoma ( ARNHL ) is correlated with CD4+ cell counts and influences antibody response to EBV [ anti-Z Epstein-Barr replicative activator ( ZEBRA ) , anti-early antigen ( EA ) , anti-viral capsid antigen ( VCA ) ] .

OBJECTIVE : To determine whether activation of Epstein-Barr virus ( EBV ) replication in <cell_type>tumour cells</cell_type> of AIDS-related non-Hodgkin 's lymphoma ( ARNHL ) is correlated with <protein>CD4+</protein> cell counts and influences antibody response to EBV [ <protein>anti-Z Epstein-Barr replicative activator</protein> ( <protein>ZEBRA</protein> ) , <protein>anti-early antigen</protein> ( <protein>EA</protein> ) , <protein>anti-viral capsid antigen</protein> ( <protein>VCA</protein> ) ] .


DESIGN : Retrospective study based on immunohistochemistry and in situ hybridization to detect EBV replicative gene products in tissue samples from patients affected by ARNHL and correlation with CD4+ cell counts and results of EBV serology ( including anti- ZEBRA activity ) in sera from the same patients .

DESIGN : Retrospective study based on immunohistochemistry and in situ hybridization to detect EBV replicative gene products in tissue samples from patients affected by ARNHL and correlation with <protein>CD4+</protein> cell counts and results of EBV serology ( including anti- <protein>ZEBRA</protein> activity ) in sera from the same patients .


METHODS : Seventeen out of 22 cases of ARNHL were selected for the presence of EBV [ Epstein-Barr early region ( EBER ) RNA-positive ] .


Immunohistochemistry was performed with anti-ZEBRA , anti-EA-restricted , anti-VCA antibodies and in situ hybridization with BHLF1/NotI oligoprobes on tumour samples .

Immunohistochemistry was performed with <protein>anti-ZEBRA</protein> , <protein>anti-EA-restricted , anti-VCA antibodies</protein> and in situ hybridization with BHLF1/NotI oligoprobes on tumour samples .


Results were statistically correlated with those of CD4+ cell counts ( 17 out of 17 ) and with anti-EBV antibody titres ( 13 out of 17 ) assessed using standard immunofluorescence method and enzyme-linked immunosorbent assay procedure using recombinant ZEBRA protein and synthetic peptides as antigens .

Results were statistically correlated with those of <protein>CD4+</protein> cell counts ( 17 out of 17 ) and with anti-EBV antibody titres ( 13 out of 17 ) assessed using standard immunofluorescence method and enzyme-linked immunosorbent assay procedure using <protein>recombinant ZEBRA protein</protein> and synthetic peptides as <protein>antigens</protein> .


RESULTS : BZLF1 ( ZEBRA ) or early gene products ( EA-R and EA-D/BHLF1/NotI ) were detected in a small proportion ( < 0.01-5 % ) of tumour cells in eight of these 17 cases by immunohistochemistry and in situ hybridization .

RESULTS : <protein>BZLF1</protein> ( <protein>ZEBRA</protein> ) or <protein>early gene products</protein> ( <protein>EA-R</protein> and <protein>EA-D/BHLF1/NotI</protein> ) were detected in a small proportion ( < 0.01-5 % ) of <cell_type>tumour cells</cell_type> in eight of these 17 cases by immunohistochemistry and in situ hybridization .


Demonstration of replicative gene expression did not correlate with either low CD4+ cell counts ( P > 0.05 ) or anti-EBV antibody titres ( P > 0.05 ) .

Demonstration of replicative gene expression did not correlate with either low <protein>CD4+</protein> cell counts ( P > 0.05 ) or anti-EBV antibody titres ( P > 0.05 ) .


Anti- ZEBRA activity was not significantly increased in patients affected with ARNHL , the cells of which expressed replicative gene products ( P > 0.05 ) .

Anti- <protein>ZEBRA</protein> activity was not significantly increased in patients affected with ARNHL , the cells of which expressed replicative gene products ( P > 0.05 ) .


CONCLUSION : The degree of immunodeficiency does not clearly enhance replicative gene expression in tumour cells of ARNHL .

CONCLUSION : The degree of immunodeficiency does not clearly enhance replicative gene expression in <cell_type>tumour cells</cell_type> of ARNHL .


EBV serology , including anti- ZEBRA activity , is not a reliable tool for predicting the occurrence of such proliferations .

EBV serology , including anti- <protein>ZEBRA</protein> activity , is not a reliable tool for predicting the occurrence of such proliferations .


Effects of prostaglandin E2 on Th0-type human T cell clones : modulation of functions of nuclear proteins involved in cytokine production .

Effects of <protein>prostaglandin E2</protein> on <cell_line>Th0-type human T cell clones</cell_line> : modulation of functions of <protein>nuclear proteins</protein> involved in <protein>cytokine</protein> production .


The effects of prostaglandin E2 ( PGE2 ) on cytokine production and proliferation of the CD4+ human helper T cell clone SP-B21 were investigated .

The effects of <protein>prostaglandin E2</protein> ( <protein>PGE2</protein> ) on <protein>cytokine</protein> production and proliferation of the <cell_line>CD4+ human helper T cell clone SP-B21</cell_line> were investigated .


In cells stimulated with anti-CD3 mAb , PGE2 inhibited cell proliferation and the production of all the cytokines examined .

In cells stimulated with <protein>anti-CD3 mAb</protein> , <protein>PGE2</protein> inhibited cell proliferation and the production of all the <protein>cytokines</protein> examined .


Addition of rIL-2 fully restored the proliferative response and partially restored the production of IL-4 and IL-5 , but not that of other cytokines .

Addition of <protein>rIL-2</protein> fully restored the proliferative response and partially restored the production of <protein>IL-4</protein> and <protein>IL-5</protein> , but not that of other <protein>cytokines</protein> .


In contrast , in cells stimulated with phorbol myristate acetate ( PMA ) /A23187 , PGE2 enhanced the production of IL-4 and IL-5 , and only partially inhibited the production of other cytokines .

In contrast , in cells stimulated with phorbol myristate acetate ( PMA ) /A23187 , <protein>PGE2</protein> enhanced the production of <protein>IL-4</protein> and <protein>IL-5</protein> , and only partially inhibited the production of other <protein>cytokines</protein> .


Therefore , the effects of PGE2 vary depending on the mode of T cell activation , and the IL-4 and IL-5 are regulated differently from other cytokines .

Therefore , the effects of <protein>PGE2</protein> vary depending on the mode of T cell activation , and the <protein>IL-4</protein> and <protein>IL-5</protein> are regulated differently from other <protein>cytokines</protein> .


In a mobility shift assay , only the NF-kappa B ( p50/p50 ) homodimer was observed in a complex formed with the kappa B sequence in unstimulated SP-B21 cells .

In a mobility shift assay , only the <protein>NF-kappa B ( p50/p50 ) homodimer</protein> was observed in a complex formed with the <dna>kappa B sequence</dna> in unstimulated SP-B21 cells .


When cells were stimulated with anti-CD3 mAb or PMA/A23187 , a complex formation of NF-kappa B ( p50 /p65 ) heterodimer with the kappa B sequence was induced .

When cells were stimulated with <protein>anti-CD3 mAb</protein> or PMA/A23187 , a complex formation of <protein>NF-kappa B</protein> ( <protein>p50</protein> <protein>/p65</protein> ) heterodimer with the <dna>kappa B sequence</dna> was induced .


Interestingly , PGE2 or di-butyryl ( Bt2 ) cAMP abolished the binding of NF-kappa B ( p50/p65 ) heterodimer to the kappa B sequence in cells stimulated with anti-CD3 mAb but not with PMA/A23187 .

Interestingly , <protein>PGE2</protein> or di-butyryl ( Bt2 ) cAMP abolished the binding of <protein>NF-kappa B ( p50/p65 ) heterodimer</protein> to the <dna>kappa B sequence</dna> in cells stimulated with <protein>anti-CD3 mAb</protein> but not with PMA/A23187 .


Our results suggest that the target of PGE2 action is a component in the signal transduction pathway leading to the activation of protein kinase C .

Our results suggest that the target of <protein>PGE2</protein> action is a component in the signal transduction pathway leading to the activation of <protein>protein kinase C</protein> .


However , the inhibition of the T cell activation signals by PGE2 is selective .

However , the inhibition of the T cell activation signals by <protein>PGE2</protein> is selective .


PGE2 enhanced the complex formation with NF-AT , AP-1 and CLE0 sequences when the cells were activated by either anti-CD3 mAb or PMA/A23187 stimulation .

<protein>PGE2</protein> enhanced the complex formation with <dna>NF-AT , AP-1 and CLE0 sequences</dna> when the cells were activated by either <protein>anti-CD3 mAb</protein> or PMA/A23187 stimulation .


It seems therefore that PGE2 , by elevating cAMP levels , interferes with the activation pathway for NF-kappa B but not for NF-AT , AP-1 or CLE0 binding protein .

It seems therefore that <protein>PGE2</protein> , by elevating cAMP levels , interferes with the activation pathway for <protein>NF-kappa B</protein> but not for <protein>NF-AT</protein> , <protein>AP-1</protein> or <protein>CLE0 binding protein</protein> .


Characterization of NF ( P ) , the nuclear factor that interacts with the regulatory P sequence ( 5'-CGAAAATTTCC-3 ' ) of the human interleukin-4 gene : relationship to NF-kappa B and NF-AT .

Characterization of <protein>NF ( P )</protein> , the <protein>nuclear factor</protein> that interacts with the regulatory <dna>P sequence</dna> ( 5'-CGAAAATTTCC-3 ' ) of the <dna>human interleukin-4 gene</dna> : relationship to <protein>NF-kappa B</protein> and <protein>NF-AT</protein> .


The P sequence of the human interleukin-4 ( IL-4 ) gene , which was defined as a responsive element for phorbol 12-myristate 13-acetate and calcium ionophore ( A23187 ) in Jurkat T cells , shares sequence similarity with the NF-kappa B and the NF-AT binding sites .

The <dna>P sequence</dna> of the <dna>human interleukin-4 ( IL-4 ) gene</dna> , which was defined as a <dna>responsive element</dna> for phorbol 12-myristate 13-acetate and calcium ionophore ( A23187 ) in <cell_line>Jurkat T cells</cell_line> , shares sequence similarity with the <dna>NF-kappa B and the NF-AT binding sites</dna> .


We examined whether NF ( P ) , a nuclear factor specific for the P sequence , is related to NF-kappa B and NF-AT .

We examined whether <protein>NF ( P )</protein> , a <protein>nuclear factor</protein> specific for the <dna>P sequence</dna> , is related to <protein>NF-kappa B</protein> and <protein>NF-AT</protein> .