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At least 847 records · Page 47Linked to original sources
PubMed1999

Specificity in transforming growth factor beta-induced transcription of the plasminogen activator inhibitor-1 gene: interactions of promoter DNA, transcription factor muE3, and Smad proteins.

Transforming growth factor beta (TGF-beta) regulates a broad range of biological processes, including cell growth, development, differentiation, and immunity. TGF-beta signals through its cell surface receptor serine kinases that phosphorylate Smad2 or Smad3 proteins. Because Smad3 and its partner Smad4 bind to only 4-bp Smad binding elements (SBEs) in DNA, a central question is how specificity of TGF-beta-induced transcription is achieved. We show that Smad3 selectively binds to two of the three SBEs in PE2.1, a TGF-beta-inducible fragment of the plasminogen activator inhibitor-1 promoter, to mediate TGF-beta-induced transcription; moreover, a precise 3-bp spacer between one SBE and the E-box, a binding site for transcription factor muE3 (TFE3), is essential for TGF-beta-induced transcription. Whereas an isolated Smad3 MH1 domain binds to TFE3, TGF-beta receptor-mediated phosphorylation of full-length Smad3 enhances its binding to TFE3. Together, these studies elucidate an important mechanism for specificity in TGF-beta-induced transcription of the plasminogen activator inhibitor-1 gene.

Base Sequence↗
PubMed1995

Redundant domains contribute to the transcriptional activity of the thyroid transcription factor 1.

The thyroid transcription factor 1 (TTF-1) is a homeodomain-containing protein implicated in the activation of thyroid-specific gene expression. Here we report that TTF-1 is capable of activating transcription from thyroglobulin and, to a lesser extent, thyroperoxidase gene promoters in nonthyroid cells. Full transcriptional activation of the thyroglobulin promoter by TTF-1 requires the presence of at least two TTF-1 binding sites. TTF-1 activates transcription via two functionally redundant transcriptional activation domains that as suggested by competition experiments, could use a common intermediary factor.

Animals↗
PubMed1995

The general transcription-repair factor TFIIH is recruited to the excision repair complex by the XPA protein independent of the TFIIE transcription factor.

Recent studies have revealed that the general transcription factor TFIIH is also a general excision repair factor which, along with several other proteins, is required for transcription-independent excision reaction. As a general transcription factor, TFIIH is recruited to RNA polymerase II-promoter complex by another general transcription factor called TFIIE. We were interested in knowing whether TFIIE is also involved in recruiting TFIIH to the excision repair complex. We found that cell-free extract depleted of TFIIE carried out excision repair at a normal rate, leading us to conclude that TFIIE is not involved in recruiting TFIIH to the damage site and has no role in general excision repair. In contrast, the human damage recognition protein XPA specifically binds to TFIIH and apparently recruits it to the damage site. The carboxyl-terminal half of XPA is responsible for specific interaction with TFIIH. The C261S/C264S mutant of XPA bound the ERCC1-XPF complex normally, but failed to bind TFIIH and failed to complement an XP-A mutant cell-free extract indicating that the XPA-TFIIH interaction is essential to effecting the excision reaction. Interestingly, XPA also binds to the p34 subunit of TFIIE specifically and in competition with the p56 subunit of TFIIE. This latter interaction has no apparent role in general excision repair but may be relevant in the transcription-coupled repair reaction.

Amino Acid Sequence↗
PubMed1996

Two separate signal transducer and activator of transcription proteins regulate transcription of the serine proteinase inhibitor-3 gene in hepatic cells.

The serine proteinase inhibitor (SPI-3) gene expression is transcriptionally regulated by interleukin (IL)-6 and glucocorticoids in hepatic cells. To identify the transcription factors involved in regulation of the SPI-3 promoter-chloramphenicol acetyltransferase constructs we overexpressed Signal Transducer and Activator of Transcription (STAT) proteins (STAT1, STAT3, STAT5B, and STAT6) and CAAT enhancer-binding protein beta. Specific signaling pathways were activated by cointroduced receptors for growth hormone, IL-3, IL-4, or chimeric receptors containing the cytoplasmic domain of gp130. STAT3 and STAT5B induced transcription via the SPI-3 promoter. The STAT5B response was substantially enhanced by truncation of the 5'-flanking region from -1021 to -148. The responsiveness to STAT3 and STAT5B required the STAT binding element at -132 to -124. This element was sufficient to confer regulation onto a heterologous promoter gene construct. In contrast, overexpression of CAAT enhancer-binding protein beta reduced the transcriptional activity of the SPI-3 promoter, presumably by interfering with STAT protein binding to the promoter element. The SPI-3 gene is the first example of an acute phase gene that is responsive to both STAT3 and STAT5B.

Animals↗
PubMed1996

p202, an interferon-inducible modulator of transcription, inhibits transcriptional activation by the p53 tumor suppressor protein, and a segment from the p53-binding protein 1 that binds to p202 overcomes this inhibition.

p202, an interferon-inducible murine protein, is a member of the "200 family" of proteins and is primarily nuclear. p202 is a modulator of transcription; it binds several transcription factors, including NF-kappaB p50 and p65, AP-1 c-Fos and c-Jun, and E2F1, and inhibits their transcriptional activity. p202 also binds pRb, the retinoblastoma protein, and if overexpressed it retards cell proliferation. Here we report that using the yeast two-hybrid assay we found that p202 bound the murine homolog of the human p53-binding protein 1 (53BP1), a protein shown to interact with the DNA binding domain of the p53 tumor suppressor protein. p202 bound a 98amino acid segment from 53BP1. This binding was inhibited by the replacement in p202 of a histidine (from the M(F/L)HATVA(T/S) sequence that is conserved among all of the 200 family proteins) by phenylalanine. We also report that overexpression of p202 inhibited the p53-dependent expression of reporter genes containing p53-activable segments from the mdm2 and p21 genes, whereas a decrease in the p202 level (in consequence of the expression of 202 antisense RNA) resulted in an increase in the p53-dependent expression of these reporters. Expression of the 53BP1 segment binding to p202 overcame the inhibition by overexpressed p202 of the transcription of reporters mediated by the p53 or the AP-1 transcription factors and of the proliferation of yeast.

Amino Acid Sequence↗
PubMed1997

Mutations in the 1,25-dihydroxyvitamin D3 receptor identifying C-terminal amino acids required for transcriptional activation that are functionally dissociated from hormone binding, heterodimeric DNA binding, and interaction with basal transcription factor IIB, in vitro.

To investigate a potential ligand-dependent transcriptional activation domain (AF-2) in the C-terminal region of the human vitamin D receptor (hVDR), two conserved residues, Leu-417 and Glu-420, were replaced with alanines by site-directed mutagenesis (L417A and E420A). Transcriptional activation in response to 1, 25-dihydroxyvitamin D3 (1,25-(OH)2D3) was virtually eliminated when either point mutant was transfected into several mammalian cell lines. Furthermore, both mutants exhibited a dominant negative phenotype when expressed in COS-7 cells. Scatchard analysis at 4 degrees C and a ligand-dependent DNA binding assay at 25 degrees C revealed essentially normal 1,25-(OH)2D3 binding for the mutant hVDRs, which were also equivalent to native receptor in associating with the rat osteocalcin vitamin D responsive element as a presumed heterodimer with retinoid X receptor. Glutathione S-transferase-human transcription factor IIB (TFIIB) fusion protein linked to Sepharose equally coprecipitated the wild-type hVDR and the AF-2 mutants. These data implicate amino acids Leu-417 and Glu-420, residing in a putative alpha-helical region at the extreme C terminus of hVDR, as critical in the mechanism of 1, 25-(OH)2D3-stimulated transcription, likely mediating an interaction with a coactivator(s) or a component of the basal transcriptional machinery distinct from TFIIB.

Amino Acid Sequence↗
PubMed1997

Functional interactions between the estrogen receptor and the transcription activator Sp1 regulate the estrogen-dependent transcriptional activity of the vitellogenin A1 io promoter.

Two distinct, TATA box-containing promoters regulate the transcriptional activity of the Xenopus vitellogenin A1 gene. These two promoters are of different strength and are separated by 1.8 kilobase pairs of untranslated sequence. Estrogen receptor (ER) and its ligand, 17beta-estradiol, induce the activity of both promoters. The estrogen response elements (EREs) are located proximal to the downstream i promoter while no ERE-like sequences have been identified in the vicinity of the upstream io promoter. We show here, that transcriptional activity of the upstream io promoter is Sp1-dependent. Moreover, we demonstrate that estrogen inducibility of the io promoter results from functional interactions between the io bound Sp1 and the ER bound at the proximity of i. Functional interactions between Sp1 and ER do not require the presence of a TATA box for transcriptional activation, as is demonstrated using the acyl-CoA oxidase promoter. The relative positions that ER and Sp1 occupy with respect to the initiation site determines whether these two transcription activators can synergize for transcription initiation.

Animals↗
PubMed1997

Transcriptional control of the forkhead thyroid transcription factor TTF-2 by thyrotropin, insulin, and insulin-like growth factor I.

The hormonal regulation of both thyroglobulin and thyroperoxidase promoter activity in FRTL-5 thyroid cells takes place, at least in part, through a hormone-responsive element to which the thyroid transcription factor TTF-2 binds. The TTF-2 cDNA, encoded by the titf2 locus, has recently been cloned and classified as a member of the forkhead transcription factor family. Here, we demonstrate that TTF-2 mRNA levels become undetectable in FRTL-5 thyroid cells cultured for 4 days in 0.2% serum and in the absent of thyrotropin (TSH) and insulin. Addition of TSH, insulin or insulin-like growth factor I (IGF-I) to the culture medium increases the levels of this transcription factor in a dose- and time- dependent manner and requires ongoing protein synthesis. The TSH effect is greater than that produced by insulin or IGF-I and is similar to the effect produced by the cAMP analog forskolin. The TSH and insulin effects are additive. In all cases, the mRNA levels increase is accompanied by an increase in transcription rate, as demonstrated by run-off assays. These data demonstrate that the TTF-2 mRNA is under tight hormonal control. This is consistent with an important role for TTF-2 as a mediator of the transcriptional activation of thyroid-specific genes (thyroglobulin and thyroperoxidase) by TSH via cAMP and by insulin through the IGF-I receptor.

Colforsin↗
PubMed1998

p38 Mitogen-activated protein kinase mediates the transcriptional induction of the atrial natriuretic factor gene through a serum response element. A potential role for the transcription factor ATF6.

In various cell types certain stresses can stimulate p38 mitogen-activated protein kinase (p38 MAPK), leading to the transcriptional activation of genes that contribute to appropriate compensatory responses. In this report the mechanism of p38-activated transcription was studied in cardiac myocytes where this MAPK is a key regulator of the cell growth and the cardiac-specific gene induction that occurs in response to potentially stressful stimuli. In the cardiac atrial natriuretic factor (ANF) gene, a promoter-proximal serum response element (SRE), which binds serum response factor (SRF), was shown to be critical for ANF induction in primary cardiac myocytes transfected with the selective p38 MAPK activator, MKK6 (Glu). This ANF SRE does not possess sequences typically required for the binding of the Ets-related ternary complex factors (TCFs), such as Elk-1, indicating that p38-mediated induction through this element may take place independently of such TCFs. Although p38 did not phosphorylate SRF in vitro, it efficiently phosphorylated ATF6, a newly discovered SRF-binding protein that is believed to serve as a co-activator of SRF-inducible transcription at SREs. Expression of an ATF6 antisense RNA blocked p38-mediated ANF induction through the ANF SRE. Moreover, when fused to the Gal4 DNA-binding domain, an N-terminal 273-amino acid fragment of ATF6 was sufficient to support trans-activation of Gal4/luciferase expression in response to p38 but not the other stress kinase, N-terminal Jun kinase (JNK); p38-activating cardiac growth promoters also stimulated ATF6 trans-activation. These results indicate that through ATF6, p38 can augment SRE-mediated transcription independently of Ets-related TCFs, representing a novel mechanism of SRF-dependent transcription by MAP kinases.

Activating Transcription Factor 6↗
PubMed2000

A testis-specific transcription factor IIA (TFIIAtau) stimulates TATA-binding protein-DNA binding and transcription activation.

The general transcription factor IIA (TFIIA) stimulates RNA polymerase II-specific transcription by stabilizing the association of the TATA-binding protein (TBP) with promoter DNA, inhibiting repressors of TBP, and facilitating activator-dependent conformational changes in the preinitiation complex. TFIIA is encoded by two genes (alphabeta and gamma) that are highly conserved between human and yeast. Here, we report the molecular cloning of a novel human gene that shares significant sequence similarity to the evolutionarily conserved amino- and carboxyl-terminal domains of TFIIAalphabeta. The TFIIA-related protein (TFIIAtau) was cloned from a testis-specific cDNA library, and its mRNA is expressed predominantly in testis tissue as determined by expressed sequence tag data base analysis and Northern blotting analysis. The TFIIA complex reconstituted with the testis-specific subunit, TFIIA (tau+gamma), formed the TFIIA-TBP-TATA DNA (T-A) and TFIIA-TFIIB-TBP-TATA DNA (TAB) complexes indistinguishably from TFIIA (alphabeta+gamma). TFIIA (tau+gamma) supported basal and activated transcription for most activators in reactions reconstituted with TFIIA-depleted nuclear extracts. However, TFIIA (tau+gamma) was reduced relative to TFIIA (alphabeta+gamma) for stimulating transcription with at least one activator, suggesting that these two forms of TFIIA have activator specificity. These results suggest that TFIIAtau may be important for testis-specific transcription regulation.

Amino Acid Sequence↗
PubMed2000

Synergism between transcription factors TFE3 and Smad3 in transforming growth factor-beta-induced transcription of the Smad7 gene.

Activation of transforming growth factor-beta (TGF-beta) receptors triggers phosphorylation of Smad2 and Smad3. After binding to Smad4, the complex enters the nucleus and interacts with other transcription factors to activate gene transcription. Unlike other Smads, Smad7 inhibits phosphorylation of Smad2 and Smad3, and its transcription is induced by TGF-beta, suggesting a negative feedback loop. Here, we show that TFE3 and Smad3 synergistically mediate TGF-beta-induced transcription from the Smad7 promoter by binding to an E-box and two adjacent Smad binding elements (SBEs), respectively. A precise 3-base pair spacer between one SBE and the E-box is essential. Previously, we showed that a similar arrangement between a SBE and an E-box of an element is essential for TGF-beta-dependent transcription of the plasminogen activator inhibitor-1 gene (PAI-1) and that TGF-beta-induced phosphorylation of Smad3 triggers its association with TFE3. Thus, TFE3-Smad3 response elements may represent a common target for TGF-beta-induced gene expression.

Basic Helix-Loop-Helix Leucine Zipper Transcriptio↗
PubMed2002

The forkhead transcription factor AFX activates apoptosis by induction of the BCL-6 transcriptional repressor.

The activation of the AKT/protein kinase B kinases by mutation of the PTEN lipid phosphatase results in enhanced survival of a diversity of tumors. This resistance to apoptosis is partly accomplished by the inhibition of genetic programs induced by a subfamily of forkhead transcription factors including AFX. Here we describe an AFX-regulated pathway that appears to account for at least part of this apoptotic regulatory system. Cells induced to synthesize an active form of AFX die by activating the apoptotic death pathway. An analysis of genes regulated by AFX demonstrated that BCL-6, a transcriptional repressor, is up-regulated approximately 4-7-fold. An examination of the BCL-6 promoter demonstrated that AFX bound to specific target sites that could activate transcription. BCL-X(L), an anti-apoptotic protein, contains potential BCL-6 target sites in its promoter. An analysis of endogenous BCL-X(L) levels in AFX-expressing cells revealed enhanced down-regulation of the transcript ( approximately 1.3-1.7-fold) and protein, and BCL-6 directly binds to and suppresses the BCL-X(L) promoter. Finally, macrophages isolated from BCL-6-/- mice show enhanced survival in vitro. These results suggest that AFX regulates apoptosis in part by suppressing the levels of anti-apoptotic BCL-XL through the transcriptional repressor BCL-6.

Animals↗
PubMed2002

POZ domain transcription factor, FBI-1, represses transcription of ADH5/FDH by interacting with the zinc finger and interfering with DNA binding activity of Sp1.

The POZ domain is a protein-protein interaction motif that is found in many transcription factors, which are important for development, oncogenesis, apoptosis, and transcription repression. We cloned the POZ domain transcription factor, FBI-1, that recognizes the cis-element (bp -38 to -22) located just upstream of the core Sp1 binding sites (bp -22 to +22) of the ADH5/FDH minimal promoter (bp -38 to +61) in vitro and in vivo, as revealed by electrophoretic mobility shift assay and chromatin immunoprecipitation assay. The ADH5/FDH minimal promoter is potently repressed by the FBI-1. Glutathione S-transferase fusion protein pull-down showed that the POZ domains of FBI-1, Plzf, and Bcl-6 directly interact with the zinc finger DNA binding domain of Sp1. DNase I footprinting assays showed that the interaction prevents binding of Sp1 to the GC boxes of the ADH5/FDH promoter. Gal4-POZ domain fusions targeted proximal to the GC boxes repress transcription of the Gal4 upstream activator sequence-Sp1-adenovirus major late promoter. Our data suggest that POZ domain represses transcription by interacting with Sp1 zinc fingers and by interfering with the DNA binding activity of Sp1.

Aldehyde Oxidoreductases↗
PubMed2002

The transcriptional coactivator CREB-binding protein cooperates with STAT1 and NF-kappa B for synergistic transcriptional activation of the CXC ligand 9/monokine induced by interferon-gamma gene.

Signal transducers and activators of transcription 1 (STAT1) and NF-kappaB cooperatively regulate the expression of many inflammatory genes. In the present study, we demonstrate that the transcriptional coactivator CREB-binding protein (CBP) mediated the STAT1/NF-kappaB synergy for transcription of the gene for CXC ligand 9 (CXCL9), an interferon-gamma (IFN-gamma)-inducible chemokine. Reporter gene analysis showed that expression of CBP potentiated IFN-gamma and tumor necrosis factor (TNFalpha)-induced promoter activity and that the CBP-mediated synergy depended upon STAT1- and NF-kappaB-binding sites in the promoter. Experiments with CBP mutants indicated that the N-terminal and C-terminal regions were necessary for the transcriptional synergy, although the histone acetyltransferase activity of CBP was dispensable. A co-immunoprecipitation assay demonstrated that STAT1 and NF-kappaB RelA (p65) simultaneously associated with CBP in vivo. Furthermore, chromatin immunoprecipitation revealed that, although costimulation with IFN-gamma and TNFalpha did not cooperatively enhance the levels of acetylated histones, it did result in increased recruitment of STAT1, CBP, and RNA polymerase II at the promoter region of the CXCL 9 gene. Together, these results demonstrate that the STAT1/NF-kappaB-dependent transcriptional synergy could result from the enhanced recruitment of RNA polymerase II complex to the promoter via simultaneous interaction of CBP with STAT1 and NF-kappaB.

Acetylation↗
PubMed2003

Amino acid deprivation and endoplasmic reticulum stress induce expression of multiple activating transcription factor-3 mRNA species that, when overexpressed in HepG2 cells, modulate transcription by the human asparagine synthetase promoter.

Transcription from the ASNS (asparagine synthetase) gene is increased in response to either amino acid (amino acid response) or glucose (endoplasmic reticulum stress response) deprivation. These two independent pathways converge on the same set of genomic cis-elements within the ASNS promoter, referred to as nutrient-sensing response element-1 and -2. Chromatin immunoprecipitation analysis provides the first in vivo evidence for activating transcription factor (ATF)-3 binding to the proximal ASNS promoter containing the nutrient-sensing response element-1 sequence. Overexpression of the full-length ATF3 protein caused a concentration-dependent biphasic response in ASNS promoter-driven transcription. Both amino acid limitation and activation of the endoplasmic reticulum stress response by glucose deprivation caused an increase in ATF3 mRNA content. However, reverse transcriptase-PCR analysis revealed that the increase in the ATF3 mRNA species detected by Northern analysis actually encoded both full-length ATF3 and two predicted truncated ATF3 isoforms (ATF3deltaZip2c and ATF3deltaZip3). Based on sequence analysis, one of the predicted truncated proteins (ATF3deltaZip3) is likely incapable of binding DNA; and yet, exogenous expression of the cDNA enhanced starvation-induced or ATF4-activated ASNS transcription, possibly by sequestering corepressor proteins. Collectively, the results provide evidence for a potential role of multiple predicted ATF3 isoforms in the transcriptional regulation of the ASNS gene in response to nutrient deprivation.

Activating Transcription Factor 3↗
PubMed2003

A novel cysteine cluster in human metal-responsive transcription factor 1 is required for heavy metal-induced transcriptional activation in vivo.

Metal-responsive transcription factor 1 (MTF-1) specifically binds to metal response elements (MREs) associated with a number of metal- and stress-responsive genes. Human MTF-1 contains a cysteine-rich cluster, -632Cys-Gln-Cys-Gln-Cys-Ala-Cys638-, conserved from pufferfish to humans far removed from the MRE-binding zinc finger domain and just C-terminal to a previously mapped serine/threonine-rich transcriptional activation domain. MTF-1 proteins containing two Cys-->Ala substitutions (C632A/C634A) or a deletion in this region altogether (Delta(632-644)) are significantly impaired in their ability to induce Zn(II)- and Cd(II)-responsive transcription of a MRE-linked reporter gene in transiently transfected mouse dko7 (MTF-1-/-) cells in culture under moderate metal stress but retain the ability to drive basal levels of transcription in a MRE-dependent manner in vivo and in vitro. In addition, the mutated proteins respond to induction by Zn(II) or Cd(II) with nuclear translocation and MRE binding activities comparable with wild-type MTF-1. Attempts to rescue the Delta(632-644) deletion mutant phenotype by inserting similar Cys-rich sequences from Drosophila MTF-1 were unsuccessful, suggesting that the structure of this motif within intact human MTF-1, rather than the simple presence of multiple closely spaced Cys residues, is required for function. This cysteine cluster therefore functions at a step subsequent to nuclear translocation and MRE-binding DNA to naked promoter-containing DNA and appears to be specifically required for MTF-1 to activate transcription in the presence of inducing heavy metal ions.

Amino Acid Sequence↗
PubMed2006

The rate of c-fos transcription in vivo is continuously regulated at the level of elongation by dynamic stimulus-coupled recruitment of positive transcription elongation factor b.

In mammalian cells, multiple stimuli induce the expression of the immediate early gene c-fos. The specificity of c-fos transcriptional response depends on the activation of signaling protein kinases, transcription factors, and chromatin-modifying complexes but also on a regulated block to elongation in the first intron. Here we show by chromatin immunoprecipitation that finely tuned control of c-fos gene expression by distinct stimuli is associated with a dynamic regulation of transcription elongation and differential phosphorylation of the C-terminal domain of RNA polymerase II. Comparison of two stimuli of c-fos expression in the pituitary cell line GH4C1, namely the thyrotropin-releasing hormone versus depolarizing KCl, shows that both stimuli increase initiation, but only thyrotropin-releasing hormone is efficient to stimulate elongation and thus produce high transcription rates. To control elongation, the elongation factor P-TEFb is recruited to the 5'-end of the gene in a stimuli and time-dependent manner. Transition from initiation to elongation depends also on the dynamic recruitment of the initiation factors TFIIB and TFIIE but not TFIID, which remains constitutively bound on the promoter. It thus appears that tight coupling of signaling input to transcriptional output rate is achieved by c-fos gene-specific mechanisms, which control post-initiation steps rather than pre-initiation complex assembly.

Animals↗
PubMed1996

Transcriptional regulation of the Icam-1 gene in antigen receptor- and phorbol ester-stimulated B lymphocytes: role for transcription factor EGR1.

Intercellular adhesion molecule (ICAM) 1/CD54 plays an important role in T cell dependent B cell activation and for function of B lymphocytes as antigen-presenting cells. ICAM-1 expression is upregulated as a consequence of B lymphocyte antigen receptor (BCR) signaling, thereby serving to render antigen-stimulated B cells more receptive to T cell-mediated costimulatory signals. We have investigated BCR-induced expression of the Icam-1 gene in primary B cells and B cell lines and have found it to be dependent on BCR-induced expression of the transcription factor EGR1. Icam-1 transcription, induced by BCR cross-linking or bypassing the BCR with phorbol ester, is absent in a B cell line in which the EGR1-encoding gene (egr-1) is methylated and not expressed. A potential EGR1-binding site was located at -701 bp upstream of the murine Icam-1 gene transcription start site and shown by electrophoretic mobility shift assay to bind to murine EGR1. Mutation of this site in the context of 1.1 kb of the Icam-1 promoter significantly abrogated transcriptional induction by phorbol ester and anti-mu stimulation in primary B cells. A direct effect of EGR1 on the Icam-1 promoter is suggested by the ability of EGR1 expressed from an SV40-driven expression vector transactivate the wild-type Icam-1 promoter, whereas mutation of the EGR1 mutation of the EGR1 binding motif at -701 bp markedly compromises this induction. These data identify EGR1 as a signaling intermediate in BCR-stimulated B cell functional responses, specifically linking BCR signal transduction to induction of the Icam-1 gene. Furthermore, similar findings for BCR-induced CD44 gene induction (Maltzman, J.S., J.A. Carman, and J.G. Monroe. 1996. Role of EGR1 in regulation of stimulus-dependent CD44 transcription in B lymphocytes. Mol. Cell. Biol. In press) suggest that EGR1 may be an important signaling molecule for regulating levels of migration and adhesion molecules during humoral immune responses.

Animals↗