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Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transcription of a eukaryotic structural gene by RNA polymerase II requires the ordered assembly of general transcription factors on the promoter to form a pre-initiation complex. Here we analyze affinity-purified complexes at various stages of assembly to determine the mechanism of action of an acidic transcriptional activator. We show that the activator can function in the absence of ATP and stimulates transcription by increasing the number of functional preinitiation complexes. The activator effects this increase by recruiting the general transcription factor TFIIB to the promoter. Using protein affinity chromatography we demonstrate a specific interaction between an acidic activating region and TFIIB. Based on these combined results, we propose that TFIIB is a direct target of an acidic activator.
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PMID:Mechanism of action of an acidic transcriptional activator in vitro. 200 92

To investigate the mechanisms of transcriptional regulation of Drosophila heat shock genes we studied the activity of a heat shock promoter in vitro after reconstitution into chromatin. Increasing the duration of nucleosome assembly progressively inactivated a plasmid template when it was transcribed with extracts of either unshocked or heat-shocked Drosophila embryos, despite induction of the transcriptional activator heat shock factor. Addition of the general transcription factor IID (TFIID) before nucleosome assembly did not significantly relieve nucleosomal inhibition, but TFIID potentiated the promoter to be responsive to activation by heat shock factor in the heat shock transcription extract. The potentiation by TFIID could be related to the nucleosome-free, hypersensitive state of heat shock promoters previously observed in vivo before heat shock induction and may be necessitated by the need to expedite activation of heat shock genes in response to environmental stress.
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PMID:Heat shock-regulated transcription in vitro from a reconstituted chromatin template. 203 56

The protein kinase MO15/CDK7 has recently been shown to be associated with the general transcription factor TFIIH and to be capable of phosphorylating the RNA polymerase II carboxy-terminal domain. Here, we show that a monoclonal MO15/CDK7 antibody coimmunoprecipitates, from a rat liver nuclear extract, all components of the RNA polymerase II transcription apparatus required for initiation at the albumin and adenovirus major late promoters. The immunoprecipitate includes RNA polymerase II, TFIID, TFIIB, TFIIH, TFIIF, and TFIIE, but is devoid of transcriptional activator proteins, such as HNF1, HNF4, and C/EBP alpha. The finding of an autonomously initiating RNA polymerase II holoenzyme in mammalian cells suggests conceptual similarities between transcription initiation in prokaryotes and eukaryotes.
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PMID:A mammalian RNA polymerase II holoenzyme containing all components required for promoter-specific transcription initiation. 755 66

The mechanism by which human immunodeficiency virus type 1 Tat transactivates the long terminal repeat promoter is not understood. It is generally believed that Tat has one or more transcription factors as its cellular target. One might expect a cellular target for Tat to possess several properties, including (i) the ability to bind to the Tat activation region, (ii) the possession of a transcriptional activation domain, and (iii) the ability to contact the cellular transcription machinery. Here we describe the cloning, expression, and characterization of a human protein, termed TAP (Tat-associated protein), which possesses some of these properties. TAP is highly conserved in eukaryotes and is expressed in a variety of human tissues. The major intracellular species of TAP is a highly acidic 209-amino-acid protein that likely is formed by removal of a highly basic 70-amino-acid N-terminal segment from a primary translation product. By deletion analysis, we have identified a TAP C-terminal region rich in acidic amino acids and leucine residues which acts as a strong transcriptional activator when bound through GAL4 sites upstream of the core long terminal repeat promoter, as well as flanking sequences that mask the activation function. Amino acid substitution of two leucine residues within the core activation region results in loss of the TAP activation function. Two lines of evidence suggest that Tat interacts with TAP in vivo. First, promoter-bound Tat can recruit a TAP/VP16 fusion protein to the promoter. Second, transiently expressed Tat is found associated with endogenous TAP, as demonstrated by coimmuno-precipitation analysis. As shown in an accompanying report, the TAP activation region binds the Tat core activation region and general transcription factor TFIIB (L. Yu, P.M. Loewenstein, Z. Zhang, and M. Green, J. Virol. 69:3017-3023, 1995). These combined results suggest the hypothesis that TAP may function as a coactivator that bridges Tat to the general transcription machinery of the cell via TFIIB.
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PMID:Molecular cloning and characterization of a cellular protein that interacts with the human immunodeficiency virus type 1 Tat transactivator and encodes a strong transcriptional activation domain. 770 27

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 carboxy-terminal domain (CTD) of the largest subunit of RNA polymerase II consists of tandem repeats of a heptapeptide with the consensus YSPTSPS. It has been shown that the heptapeptide repeat interacts directly with the general transcription factor TFIID. We report here that the CTD activates transcription when fused to the DNA-binding domain of GAL4. More importantly, we find that the proline-rich transcriptional activation domain of the CCAAT-box-binding factor CTF/NF1 contains a sequence with striking similarity to the heptapeptide repeats of the CTD. We show that this CTD-like motif is essential for the transcriptional activator function of the proline-rich domain of CTF/NF1. Deletion of and point mutations in this CTD-like motif abolish the transcriptional activator function of the proline-rich domain, while natural CTD repeats from RNA polymerase II are fully functional in place of the CTD-like motif. We further show that the proline-rich activation domain of CTF/NF1 interacts directly with the TATA-box-binding protein (TBP), and that a mutation in the CTD-like motif that abolishes transcriptional activation reduces the affinity of the proline-rich domain for TBP. These results demonstrate that a class of proline-rich activator proteins and RNA polymerase II possess a common structural and functional component which can interact with the same target in the general transcription machinery. We discuss the implications of these results for the mechanisms of transcriptional activation in eucaryotes.
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PMID:The upstream activator CTF/NF1 and RNA polymerase II share a common element involved in transcriptional activation. 802 1

The p53 tumor suppressor gene product, a sequence-specific DNA-binding protein, has been shown to act as a transcriptional activator and repressor both in vitro and in vivo. Consistent with its role in regulating transcription are recent observations that the N-terminal acidic domain of p53 binds directly to the TATA box-binding protein subunit of the general transcription factor, TF IID. It is now demonstrated that wild-type p53 (wt-p53) inhibits human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR)-directed chloramphenicol acetyltransferase activity in a cotransfection assay system. Importantly, this effect of wt-p53 on the HIV-1 LTR was also demonstrated by in vitro transcription assays. In addition, the Sp1 sites and the TATA box of the HIV-1 LTR are demonstrated to be the primary sites involved with p53-induced effects on this viral promoter. The upstream elements of the HIV-1 LTR, including the nuclear factor kappa B (NF-kappa B) binding sites, decrease the p53-induced inhibitory effects on viral transcription. In the presence of the HIV-1 TAR sequence and Tat protein, the HIV-1 LTR also becomes less sensitive to wt-p53-induced inhibition. By using a retroviral vector delivery system, mutant forms of p53 genes were expressed in two HIV-1 latently infected cell lines, ACH-2 and U1. In the ACH-2 cell line, which is now demonstrated to contain an endogenous mutant form of p53 (amino acid 248, Arg to Gln), additional mutant p53 proteins did not alter HIV-1 replication. In U1 cells, which completely lack endogenous p53, overexpression of mutant p53 led to an increase in HIV-1 replication. Thus, these data indicate a possible functional role for wt-p53 and mutant p53 proteins in the control of HIV-1 replication patterns and proviral latency.
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PMID:The tumor suppressor protein p53 strongly alters human immunodeficiency virus type 1 replication. 820 5

A yeast protein has been identified that stimulates basal transcription by RNA polymerase II, binds both single- and double-stranded DNA, and interacts with both a general transcription factor and a transcriptional activator. Phosphorylation appears to regulate these interactions. The gene for the transcriptional stimulatory protein, termed TSP1, was cloned and found to be dispensable for yeast cell viability. The deduced amino acid sequence is similar to that of mammalian coactivator protein PC4.
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PMID:A yeast transcriptional stimulatory protein similar to human PC4. 870 84

The transcriptional activator p53 is known to interact with components of the general transcription factor TFIID in vitro. To examine the relevance of these associations to transcriptional activation in vivo, plasmids expressing a p53-GAL4 chimera and Drosophila TATA-binding protein (dTBP) were transfected into Drosophila Schneider cells. p53-GAL4 and dTBP displayed a markedly synergistic effect on activated transcription from a GAL4 site-containing reporter that was at least 10-fold greater than observed with other activators tested. A mutant p53 previously shown to be defective in both transcriptional activation in vivo and in binding to TBP-associated factors (TAFs) in vitro, although still capable of binding dTBP, did not cooperate with dTBP, suggesting that TAFs may contribute to this synergy. Providing further support for this possibility, transfected dTBP assembled into rapidly sedimenting complexes and could be immunoprecipitated with anti-TAF antibodies. While overexpression of any of several TAFs did not affect basal transcription, in either the presence or the absence of cotransfected dTBP, overexpression of TAFII230 inhibited transcriptional activation mediated by p53-GAL4 as well as by GAL4-VP16 and Sp1. Overexpression of TAFII40 and TAFII60 also inhibited activation by p53-GAL4 but had negligible effects on activation by GAL4-VP16 and Sp1, while TAFII110 did not affect any of the activators. TAF-mediated inhibition of activated transcription could be rescued by high levels of exogenous dTBP, which also restored full synergy. These data demonstrate for the first time that functional interactions can occur in vivo between TBP, TAFs, and p53.
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PMID:Functional interaction between p53, the TATA-binding protein (TBP), andTBP-associated factors in vivo. 875 30

The general transcription factor TFIID is composed of the TATA-box-binding protein (TBP) and a set of TBP-associated factors (TAFIIs). In vitro, TAFIIs are required for activated transcription, and have been proposed to be obligatory targets of transcriptional activator proteins (activators)2. The function of TAFIIs has not been investigated systematically in vivo. A Saccharomyces cerevisiae TAFII complex (yTAFII complex) has been identified that shares functional and structural similarities with higher eukaryotic TFIID. In particular, most yTAFIIs are the homologue of a higher eukaryotic TAFII. Here we report that inactivation or depletion of six different yTAFIIs, including the core yTAFII, that contacts TBP, does not compromise transcriptional activation. We conclude that in vivo, activated transcription of many genes can occur in the absence of functional yTAFIIS, and that in these instances another transcription component(s) must be the target of the activator.
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PMID:Transcription activation in cells lacking TAFIIS. 877 74


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