Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tax1 of human T-cell leukemia virus type 1 (HTLV-1) is a transcriptional activator for viral gene expression and is also a transforming protein through inducing the expression of several cellular genes under the control of mitogenic signals. We identified the CArG boxes as a Tax1-responsive cis-acting element for the cellular immediate early genes c-fos, egr-1, and egr-2. Using a chimeric protein consisting of the CArG-binding factor p67SRF and the heterologous DNA-binding domain of a yeast transcription factor GAL4, we demonstrated that Tax1 activates the transcriptional activity of p67SRF through the GAL4-binding site. The carboxy-terminal half of p67SRF, which lacks domains for DNA-binding, dimerization, and ternary complex formation with p62TCF, was sufficient for the activation by Tax1. Tax1 produced in Escherichia coli bound p67SRF in vitro. The complex formation in vivo was also indicated by the finding that the acidic activation domain of VP16, by fusion to p67SRF, can complement the transcriptional activation function of a mutant Tax1 in trans. Thus, Tax1 activates CArG-mediated transcription without mitogenic signals through interaction with a CArG-binding factor, p67SRF. This must be one of the primary steps by which Tax1 causes aberration in growth control of the infected cells.
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PMID:Interaction of HTLV-1 Tax1 with p67SRF causes the aberrant induction of cellular immediate early genes through CArG boxes. 142 72

Transcription of the skeletal alpha-actin gene is selectively activated in rat myocardiocytes undergoing hypertrophy both in vivo and in vitro. In most of these models, transient expression of certain proto-oncogene transcription factors precedes hypertrophy and sarcomeric gene induction. Using expression vectors encoding Fos and Jun, the main constituents of transcriptional activator protein AP-1, we analyzed the role of these oncoproteins in mediating the transcriptional induction of skeletal alpha-actin by adrenergic stimulation. Both c-fos and c-jun were induced early after beta-adrenergic stimulation, with peak mRNA levels preceding skeletal alpha-actin induction by several hours. A second peak of c-jun mRNA coincided with skeletal alpha-actin induction. Co-transfection assays in cardiac myocytes and P19 teratocarcinoma cells demonstrated that over-expression of c-jun, or c-fos plus c-jun, transactivated the skeletal alpha-actin promoter by about 5-fold. Comparable activation was not seen for alpha-myosin heavy chain or cardiac alpha-actin promoters. Skeletal alpha-actin promoter sequences between -153 and -36 were required for maximal transactivation by c-fos/c-jun, and purified Fos and Jun were bound specifically within this region. A direct physiological role is suggested for the AP-1 transcription factor complex in regulating skeletal alpha-actin gene expression and alpha-actin isoform switching during the onset of signal-mediated cardiac myocyte hypertrophy.
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PMID:Positive regulation of the skeletal alpha-actin gene by Fos and Jun in cardiac myocytes. 146 48

Several epidemiological studies have demonstrated a link between chronic B virus infection and primary hepatocellular carcinoma (PHC). HBV DNA sequence integrations into the host cell genome have often been observed in hepatocarcinoma tissues. However, since only in a few cases of PHC the target of HBV-DNA insertion has been identified, alternative mechanisms for HBV-induced hepatocyte transformation have been investigated. Like many other DNA viruses, the hepatitis B virus bears a transactivational potential. Both full length and truncated versions of HBV X protein are able to influence the expression of cellular nuclear protooncogenes c-fos and c-myc. A second transcriptional activator is encoded by the PreS/S region of HBV, but its activity on viral and cellular genes become evident only after dislocations from its downstream sequences. Thus, HBV is able to influence infected cell growth and differentiation using both native proteins, newly generated truncated proteins and virus-cell fusion polypeptides.
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PMID:Hepatitis B virus and hepatocellular carcinoma: a possible role for the viral transactivators. 166 93

Transcription of the human vasoactive intestinal peptide (VIP) gene is regulated by both cyclic AMP and phorbol esters. A 17-nucleotide enhancer element within the human VIP gene mediates transcriptional activation by both phorbol esters and forskolin. Mutations of this element decrease responses to both agents, suggesting that the trans-acting proteins that mediate both modes of transcriptional regulation have similar DNA-binding characteristics. The response of the VIP enhancer element to forskolin, but not to 12-O-tetradecanoylphorbol-13-acetate, was attenuated by treatment with a recombinant inhibitor of the cAMP-dependent protein kinase, suggesting that the cAMP-dependent protein kinase and protein kinase C second messenger pathways that converge on this single enhancer element are distinct. The transcriptional activator cAMP-responsive element-binding (CREB) proteins and the c-fos.c-Jun complex interact with the VIP enhancer. The dual second messenger responses of the VIP gene may result from the interaction of this second messenger enhancer with different transcriptional activator proteins.
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PMID:Cyclic AMP- and phorbol ester-induced transcriptional activation are mediated by the same enhancer element in the human vasoactive intestinal peptide gene. 184 91

We have cloned and sequenced a cDNA encoding gp34, a novel glycoprotein expressed in cells bearing human T-cell leukemia virus type I (HTLV-I). HTLV-I has a trans-acting transcriptional activator, p40tax, that is thought to be implicated in leukemogenesis through the activation of cellular enhancers. With a subline (JPX-9) of the human T-cell line Jurkat, in which p40tax is inducible, gp34 was shown to be of cellular origin and to be transcriptionally activated by p40tax. It was also demonstrated that two species of mRNA are generated from one copy of the gp34 gene and that these mRNAs encode the identical gp34 product and differ in the 3' untranslated region. Analysis of the deduced amino acid sequence of gp34 showed that it lacks typical signal peptides; however, it has a hydrophobic stretch for membrane anchoring and four possible N-linked glycosylation sites at the carboxy-terminal portion, indicating that it belongs to the family of membrane proteins whose carboxy-terminal portion protrudes out of the cell. The gp34 gene displayed relatively delayed induction compared with other genes activated by p40tax. Taken together with the observation of the dependence of gp34 expression on HTLV-I p40tax, unlike other p40tax-dependent genes such as those for the interleukin-2 receptor alpha chain and c-fos, which are expressed or induced under physiological conditions, we predict that the mechanism involved in the induction of gp34 expression by p40tax is distinct from and more intricate than those for the previously characterized genes.
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PMID:Molecular cloning and characterization of a novel glycoprotein, gp34, that is specifically induced by the human T-cell leukemia virus type I transactivator p40tax. 199 93

When expressed in Epstein-Barr virus (EBV) latently infected B cells, the EBV early protein EB1 trans-activates as many EBV early genes as does TPA. Several EB1 responsive elements (ZRE) have been identified in EBV early promoters and are located at relatively short distances from the TATA box. One of them (ZRE-M) overlaps with a consensus TPA responsive element (TRE) defined as an AP-1/c-jun/c-fos binding site and is located in an EBV promoter controlling the expression of the post-transcriptional activator EB2. Another (ZREZ) is located in the promoter controlling the expression of EB1 and does not respond to TPA. These two ZREs have no apparent sequence homology. Although EB1 activates transcription from the AP-1 enhancer sequence and from the ZREZ, the activation is severely impaired by distance, suggesting that EB1 is more likely to be a promoter factor than an enhancer factor. These properties also suggest that EB1 is not functionally related to c-jun and c-fos. However, since EB1 can activate transcription from AP-1 binding sites when properly positioned, the role of this factor in the oncogenic properties of EBV should be considered.
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PMID:The Epstein-Barr virus early protein EB1 activates transcription from different responsive elements including AP-1 binding sites. 254 44

The c-Myc protein is involved in cellular transformation and mitogenesis, but also works as a potent inducer of differentiation and programmed cell death. Max as an obligate heterodimeric partner for Myc mediates its functions as a specific transcriptional activator and a transforming protein. Mad and Mxi1 proteins both heterodimerize with Max and compete with each other for limiting amounts of Max. Transcriptional activation by Myc can be suppressed by increasing the amount of Mad or Mxi1. This report shows the expression pattern of these Myc related factors at the mRNA level in a small cell lung cancer (SCLC) cell line (GLC4) which is characterized by c-myc amplification and strong constitutive c-myc overexpression. We found these genes transcriptionally active but uninfluenced from high c-myc transcription. Max was constantly transcribed at a relatively low level during cell cycle progression. Mad and mxi1 mRNA was at a surprisingly high level in proliferating cells. Mad was further upregulated and mxi1 was downregulated to basal levels during serum starvation of the cells. We further analyzed the activity of c-fos, c-jun, c-myb and nm23 which are described to be involved in c-myc transcriptional activation, c-jun and c-fos were not constitutively activated and can be excluded as regulators. High steady state c-myc in contrast influences the serum stimulated transient activation mechanism of these two genes. We identified high copy number nm23 mRNA whose role as a putative c-myc transcriptional activator is under investigation. Our results indicate that constitutive overexpression of c-myc does not require the activity of the nuclear oncogenes tested and that the m-RNA expression pattern of functionally related proteins is not influenced.
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PMID:Coexpression pattern of c-myc associated genes in a small cell lung cancer cell line with high steady state c-myc transcription. 765 39

A few general transcription factors, in particular TFIID and TFIIB, have been found to bind transcriptional activators. Here we show that the general transcription factor TFIIF is also a target for a transcriptional activator, namely serum response factor (SRF), which binds to the c-fos promoter. Using a yeast interaction assay, we find that SRF binds the RAP74 subunit of TFIIF and that SRF's transcriptional activation domain is the region involved in this binding. Further, RAP74's central charged cluster domain is required for binding to SRF's activation domain. Deletion of this domain impairs RAP74's ability to support SRF-activated transcription in vitro but has little effect on the protein's basal transcription activity or its ability to support SP1-activated transcription. The correlation of SRF-RAP74 binding with transcriptional activation suggests that RAP74 is a critical target for SRF-activated transcription.
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PMID:Interaction with RAP74 subunit of TFIIF is required for transcriptional activation by serum response factor. 785 23

The c-fos serum response element (SRE) is necessary and sufficient for induction of the c-fos gene in response to serum and growth factors. This activation is dependent upon serum response factor (SRF), a transcriptional activator which binds the SRE. A factor, p62TCF, which binds in conjunction with SRF to the SRE and which is activated by mitogen-activated protein kinase, has also been implicated in c-fos regulation. By using a reporter gene system with weak SRE mutations that is dependent upon overexpression of SRF for serum induction, we have found that there are at least two pathways for serum induction that converge on the SRE. Loss of TCF binding by mutations in SRF and the SRE did not reduce serum induction of the reporter genes. We have found a pathway for serum induction that is sensitive to mutations in the A/T-containing central sequence of the SRE and which is independent of TCF. When this pathway was mutated, activation was dependent upon TCF binding, demonstrating that TCF can also function in serum induction. Both of the signalling pathways required a minimal domain of SRF. This domain, spanning SRF's DNA binding domain, was sufficient for serum induction when fused to a heterologous transcriptional activation domain.
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PMID:Two pathways for serum regulation of the c-fos serum response element require specific sequence elements and a minimal domain of serum response factor. 806 25

elk-1, an ets related gene codes for a sequence specific DNA binding transcriptional activator which in association with serum response factor (SRF) forms a ternary complex at the c-fos serum response element (SRE). Recently the C-terminal region of both elk-1 and delta elk-1 proteins was shown to undergo phosphorylation by MAP kinases and function as an activator of MAP kinases. Here we show that delta elk-1 and two other elk-1 related proteins SAP-1a and SAP-1b, like elk-1, can function as transcriptional activators. In this report we have localized the transcriptional activation domain of the SAP-1 proteins (STA) to a large portion of the carboxy terminal region and have identified two autonomous transcriptional activation domains in the elk-1 protein, one at the amino (ETA-1) and the other at the carboxy terminal region (ETA-2). delta elk-1 protein contains only the ETA-2 domain indicating differential usage of activation domains as a result of alternative splicing. We can speculate that the ETA-1 domain can function in vivo independent of ETA-2, but the ETA-2 domain can function either in the absence of ETA-1 (as seen in delta elk-1) or in the presence of accessory proteins like SRF. The role of SRF in the activation of the ternary complex might be to bind to the ETA-1 domain, somehow conceal it's activation domain and in the process unmask the ETA-2 domain (for phosphorylation by MAP kinases) and activate transcription. The ETA-1 domain may be functioning as a negative regulatory transcriptional activation domain for ETA-2. These observations suggest that the elk-1 family of proteins may not only regulate fos and MAP kinases but also other elk-1 target genes that are essential for cellular growth control.
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PMID:Transcriptional activation domains of elk-1, delta elk-1 and SAP-1 proteins. 824 51


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