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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A DNA fragment of the rat embryonic myosin heavy-chain promoter (MHCemb) has been found to specifically bind a nuclear factor (NFe) present in extracts prepared from mouse C2 myoblasts, myotubes, and HeLa cells. The nucleotide sequence of the binding site (BSe) has been identified as 5'-GTGTCAGTCA-3' and was located between -93 and -84. Transient expression studies on MHCemb promoter deletion constructs in C2 myoblasts and C2 myotubes suggested that NFe is a transcriptional factor. Deletion of the NFe-binding site resulted in four- to sixfold and twofold reduction of promoter activity in C2 myotubes and C2 myoblasts, respectively. Furthermore, point mutations at the BSe not only abolished the NFe-binding activity of the MHCemb promoter but also resulted in reduction of the promoter activity to levels similar to those of the deletion constructs in C2 myotubes, myoblasts, and Hela cells (four- to sixfold). Although BSe and the binding site of the recently identified transcriptional factors AP-1 and ATF share significant homology, the results from competition binding assays indicated that NFe is different from both AP-1 and ATF.
Mol Cell Biol 1989 May
PMID:Interaction of nuclear proteins with a positive cis-acting element of rat embryonic myosin heavy-chain promoter: identification of a new transcriptional factor. 274 36

The adenovirus early region 3 (E3) promoter is an early viral promoter which is strongly induced by the adenovirus transactivator protein E1A. DNase I footprinting with HeLa cell extracts has identified four factor-binding domains which appear to be involved in basal and E1A-induced transcriptional regulation. These binding domains may bind TATA region-binding factors (site I), the CREB/ATF protein (site II), the AP-1 protein (site III), and nuclear factor I/CTF (site IV). Recently, it has been shown that the DNA-binding domain of transcription factor AP-1 has homology with the yeast transcription factor GCN4 and that the yeast transactivator protein GAL4 is able to stimulate transcription in HeLa cells from promoters containing GAL4-binding sites. These results suggest an evolutionary conservation of both transcription factors and the mechanisms responsible for transcriptional activation in Saccharomyces cerevisiae and higher eucaryotic organisms. To determine whether similar patterns of transcriptional regulation were seen with the E3 promoter in HeLa and yeast cells, the E3 promoter fused to the chloramphenicol acetyltransferase (cat) gene was cloned into a high-copy-number plasmid and stably introduced into yeast cells. S1 analysis revealed that similar E3 promoter mRNA start sites were found in yeast and HeLa cells. DNase I footprinting with partially purified yeast extracts revealed that four regions of the E3 promoter were protected. Several of these regions were similar to binding sites determined by using HeLa cell extracts. Oligonucleotide mutagenesis of these binding domains indicated their importance in the transcriptional regulation of the E3 promoter in yeast cells. These results suggest that similar cellular transcription factor-binding sites may be involved in the regulation of promoters in both yeast and mammalian cells.
Mol Cell Biol 1988 Sep
PMID:Adenovirus transcriptional regulatory regions are conserved in mammalian cells and Saccharomyces cerevisiae. 297 53

When an in vitro assay system and radioimmunoassays specific for juvenile hormones (JH) I and III were used to probe the effect of co-incubating pupal brains with last instar larval corpora allata (CA) from the tobacco hornworm, Manduca sexta, a selective activation of JH III synthesis by the CA was observed. This homolog-specific activation suggested the presence of an allatotropic factor for the synthesis of JH III (JH III ATF), and its presence was demonstrated by the ability of a postmicrosomal supernatant of a day 0 pupal brain homogenate to activate the CA in vitro in a dose-dependent manner. This moiety appears to be a protein, based on its heat lability and protease sensitivity, and has an apparent molecular size of 40 kD and an isoelectric point of 5.5 JH III ATF activity is localized in specific neural tissues of the day 0 pupa, the brain and first three abdominal ganglia, with the brain containing 4 times the activity in the ganglia. The existence of this factor suggests that JH III synthesis by the CA of Manduca is regulated by a neuropeptide.
Mol Cell Endocrinol 1984 Oct
PMID:Activation of Manduca sexta corpora allata in vitro by a cerebral neuropeptide. 650 Jan 72

The X-ray structure of the GCN4-bZIP protein bound to DNA containing the ATF/CREB recognition sequence has been refined at 2.2 A. The water-mediated interactions between the basic domain and DNA are revealed, and combined with a more accurate description of the direct contacts, further clarify how binding specificity is achieved. Water molecules extend the interactions of both invariant basic domain residues, asparagine 235 and arginine 243, beyond their direct base contacts. The slight bending of the basic domain alpha-helix around the DNA facilitates the linking of arginine 241, 243 and 245 to main-chain carbonyl oxygen atoms via water molecules, apparently stabilizing interactions with the DNA.
J Mol Biol 1995 Dec 08
PMID:Crystal structure of a bZIP/DNA complex at 2.2 A: determinants of DNA specific recognition. 750 Mar 40

Cytokine-induced expression of the E-selectin gene requires the promoter binding and interaction of the transcription factors NF-kappa B and ATF. Here we have further analyzed the E-selectin promoter and revealed an additional region (nucleotides -140 to -105 [-140/-105]) which is essential in controlling promoter activation by cytokines. We identified high-mobility-group protein I(Y) [HMG-I(Y)] interacting specifically at two sites within this region. We noted that one of the HMG-I(Y)-binding sites overlaps a sequence element (-127/-118) diverging at only one position from the NF-kappa B consensus binding sequence. This led us to ask whether the -127/-118 element represents a second functional NF-kappa B-binding site within the E-selectin promoter. Using specific antisera, we show that p50, p65, and, interestingly, RelB are components of the complex interacting at this site. Mutational analysis of the -127/-118 NF-kappa B site indicates that both NF-kappa B and HMG-I(Y) binding at this site are essential for interleukin-1 induction of the promoter. We demonstrate that the binding affinity of the p50 subunit of NF-kappa B to both NF-kappa B sites within the E-selectin promoter is significantly enhanced by HMG-I(Y). In addition, an essential role for cooperative interaction between the two NF-kappa B complexes is shown by the requirement for both NF-kappa B sites to mediate E-selectin promoter activation by interleukin-1 and p50/p65 expression. We conclude that HMG-I(Y) mediates binding of a distinct NF-kappa B complex at two sites within the E-selectin promoter. Furthermore, a unique cooperativity between these NF-kappa B complexes is essential for induced E-selectin expression. These results suggest mechanisms by which NF-kappa B complexes are involved in specific gene activation.
Mol Cell Biol 1994 Sep
PMID:Cooperativity between two NF-kappa B complexes, mediated by high-mobility-group protein I(Y), is essential for cytokine-induced expression of the E-selectin promoter. 752 May 24

Transcription of the endothelial leukocyte adhesion molecule 1 (E-selectin or ELAM-1) gene is induced by the inflammatory cytokines interleukin-1 beta and tumor necrosis factor alpha (TNF-alpha). In this report, we identify four positive regulatory domains (PDI to PDIV) in the E-selectin promoter that are required for maximal levels of TNF-alpha induction in endothelial cells. In vitro DNA binding studies reveal that two of the domains contain novel adjacent binding sites for the transcription factor NF-kappa B (PDIII and PDIV), a third corresponds to a recently described CRE/ATF site (PDII), and a fourth is a consensus NF-kappa B site (PDI). Mutations that decrease the binding of NF-kappa B to any one of the NF-kappa B binding sites in vitro abolished cytokine-induced E-selectin gene expression in vivo. Previous studies demonstrated a similar correlation between ATF binding to PDII and E-selectin gene expression. Here we show that the high-mobility-group protein I(Y) [HMG I(Y)] also binds specifically to the E-selectin promoter and thereby enhances the binding of both ATF-2 and NF-kappa B to the E-selectin promoter in vitro. Moreover, mutations that interfere with HMG I(Y) binding decrease the level of cytokine-induced E-selectin expression. The organization of the TNF-alpha-inducible element of the E-selectin promoter is remarkably similar to that of the virus-inducible promoter of the human beta interferon gene in that both promoters require NF-kappa B, ATF-2, and HMG I(Y). We propose that HMG I(Y) functions as a key architectural component in the assembly of inducible transcription activation complexes on both promoters.
Mol Cell Biol 1994 Oct
PMID:A striking similarity in the organization of the E-selectin and beta interferon gene promoters. 752 51

Embryonal carcinoma (EC) cells and embryonic stem (ES) cells provide useful model systems for studying differentiation during early mammalian development. Previous studies have demonstrated that differentiation of two restricted mouse EC cell lines is accompanied by activation of the TGF-beta 2 gene. Moreover, one negative and two positive regulatory regions upstream of the transcription start site were identified, which appear to play key roles in the transcriptional regulation of the human TGF-beta 2 gene. In this report, we demonstrate that the same three regulatory regions strongly influence the activity of the TGF-beta 2 promoter in differentiated cells derived from the multipotent human EC cell line, NT2/D1, and from the murine totipotent ES cell line, CCE. We also determined that the same three regions are active in the regulation of the TGF-beta 2 gene in the murine parietal endoderm-like cell line, PYS-2. However, an additional negative regulatory region appears to contribute to the regulation of the TGF-beta 2 gene in PYS-2 cells. Last, mutation of a CRE/ATF element located just upstream of the transcription start site of the TGF-beta 2 gene reduces significantly the activity of the TGF-beta 2 promoter in the differentiated cells. However, in contrast to our previous findings, our gel mobility shift analyses demonstrate that this CRE/ATF element is bound by similar proteins in nuclear extracts prepared from undifferentiated and differentiated mouse EC cells as well as from undifferentiated human EC cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Reprod Dev 1995 Jun
PMID:Cis-regulatory elements and transcription factors involved in the regulation of the transforming growth factor-beta 2 gene. 765 67

Glucocorticoid induction of the tyrosine aminotransferase gene deviates from that of many glucocorticoid-responsive genes by having a lower EC50 and displaying more agonist activity with a given antiglucocorticoid. A cis-acting element, located 3646 base pairs upstream of the start of tyrosine aminotransferase gene transcription, has been found to be sufficient to reproduce these variations with heterologous genes and promoters (Oshima, H., and Simons, S.S., Jr. (1992) Mol. Endocrinol. 6, 416-428). This element has been called a glucocorticoid modulatory element, or GME. Others have called this sequence a cyclic AMP-responsive element (CRE) due to the binding of the cyclic AMP response element binding protein (CREB). We now report the partial purification and characterization of two new proteins (GMEB1 and -2) of 88 and 67 kDa that bind to the GME/CRE as a heteromeric complex. This purification was followed by the formation of a previously characterized, biologically relevant band in gel shift assays. By several biochemical criteria, the GMEBs differed from many of the previously described CREB/CREM/ATF family members. Partial peptide sequencing revealed that the sequences of these two proteins have not yet been described. Size exclusion chromatography and molecular weight measurements of the gel-shifted band demonstrated that the GMEBs bound to the GME as a macromolecular complex of about 550 kDa that could be dissociated by deoxycholate. Similar experiments showed that CREB bound to the GME as heteromeric complexes of about 310 and 360 kDa. As determined from gel shift assays, GMEB1 and -2 are not restricted to rat liver cells but appear to be ubiquitous. Thus, these novel GMEBs may participate in a similar modulation of other glucocorticoid-inducible genes in a variety of cells.
 ...
PMID:The factor binding to the glucocorticoid modulatory element of the tyrosine aminotransferase gene is a novel and ubiquitous heteromeric complex. 766 13

We previously reported that NF-kappa B and a complex we referred to as NF-ELAM1 play a central role in cytokine-induced expression of the E-selectin gene. In this study we identify cyclic AMP (cAMP)-independent members of the ATF family binding specifically to the NF-ELAM1 promoter element. The NF-ELAM1 element (TGACATCA) differs by a single nucleotide substitution from the cAMP-responsive element consensus sequence. We demonstrate that this sequence operates in a cAMP-independent manner to induce transcription and thus define it as a non-cAMP-responsive element (NCRE). We show that ATFa is a component of the NF-ELAM1 complex and its overexpression activates the E-selectin promoter. In addition, ATFa, ATF2, and ATF3 interact directly with NF-kappa B in vitro, linking two unrelated families of transcription factors in a novel protein-protein interaction. Furthermore, we demonstrate that the ability of overexpressed NF-kappa B to transactivate the E-selectin promoter in vivo is dependent on the NF-ELAM1 complex. Our results suggest that a direct interaction between ATFs and NF-kappa B is, at least in part, the mechanism by which these factors specifically regulate E-selectin promoter activity.
Mol Cell Biol 1993 Nov
PMID:Cyclic AMP-independent ATF family members interact with NF-kappa B and function in the activation of the E-selectin promoter in response to cytokines. 769 36

Previous studies demonstrated that differentiation of embryonal carcinoma (EC) cells increases the expression of the TGF-beta 2 gene and identified a CRE/ATF-like motif in the TGF-beta 2 promoter that is necessary for its activity. This suggested that differentiation may increase the transcription of this gene by differential binding of transcription factors to the CRE/ATF-like motif. To test this possibility, we performed gel mobility shift analysis using double-stranded oligodeoxynucleotides containing the TGF-beta 2 CRE/ATF-like motif and nuclear extracts prepared from F9 EC cells and F9-differentiated cells. We determined that the DNA/protein complexes formed by the EC nuclear extracts, but not the complexes formed by differentiated cell nuclear extracts, are recognized and supershifted by an ATF-1 specific antibody. This observation is consistent with our Western immunoblot analysis that detects AFT-1 in the EC cells, but not in their differentiated counterparts. In addition, we provide evidence that protein phosphorylation influences the formation of complexes between F9 nuclear proteins and the CRE/ATF-like motif. Together, our studies identify a likely role for the CRE/ATF-like motif in the regulation of TGF-beta 2 and suggest that this site binds one set of nuclear proteins in EC cells, where the gene is not expressed, and a different set of nuclear proteins in the differentiated cells, where the gene is expressed.
Mol Reprod Dev 1995 Feb
PMID:Regulation of the transforming growth factor-beta 2 gene promoter in embryonal carcinoma cells and their differentiated cells: differential utilization of transcription factors. 776 6


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