Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20226 (TATA-binding protein)
 1,297 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Infection of HeLa cells with poliovirus leads to rapid shut-off of host cell transcription by RNA polymerase II. Previous results have suggested that both the basal transcription factor TBP (TATA-binding protein) and transcription activator proteins such as CREB (cyclic AMP-responsive element-binding protein) and Oct-1 (the octamer-binding factor) are cleaved by the viral-encoded protease, 3C(Pro). Here we demonstrate that the transcriptional activator (and tumor suppressor) p53 is degraded by the viral protease 3C both in vivo and in vitro. Unlike other transcription factors that are directly cleaved by 3C(pro), degradation of p53 requires a HeLa cell activity in addition to 3C(Pro). The degradation of p53 by 3C(Pro) does not appear to involve the ubiquitin pathway of protein degradation. Vaccinia virus infection of HeLa cells leads to inactivation of the cellular activity required for 3C(Pro)-mediated degradation of p53. The vaccinia-encoded protein (CrmA) is known to inhibit caspase I (ICE protease) that converts inactive IL-1beta to an active secreted form. Incubation of HeLa cells with caspase I inhibitor Z-VAD-fmk does not interfere with 3C(Pro)-mediated degradation of p53. The cellular activity present in extracts of HeLa cells can be fractionated through phosphocellulose. A partially purified fraction that elutes at 0.6 M KCl from phosphocellulose contains the activity that degrades p53 in a 3C(Pro)-dependent manner. These results suggest that both poliovirus-encoded protease 3C(Pro) and a cellular activity are required for the degradation of p53 observed in cells infected with poliovirus.
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PMID:Poliovirus 3C protease-mediated degradation of transcriptional activator p53 requires a cellular activity. 1187 95

Expression of the prosurvival Bcl-2 homologue Bfl-1/A1 is induced by NF-kappa B-activating stimuli, while B and T cells from c-rel knockout mice show an absolute defect in bfl-1/a1 gene activation. Here, we demonstrate NF-kappa B-dependent assembly of an enhanceosome-like complex on the promoter region of bfl-1. Binding of NF-kappa B subunit c-Rel to DNA nucleated the concerted binding of transcription factors AP-1 and C/EBP beta to the 5'-regulatory region of bfl-1. Optimal stability of the complex was dependent on proper orientation and phasing of the NF-kappa B site. Chromatin immunoprecipitation analyses demonstrated that T-cell activation triggers in vivo binding of endogenous c-Rel, c-Jun, C/EBP beta, and HMG-IC to the bfl-1 regulatory region, coincident with selective recruitment of coactivators TAFII250 and p300, SWI/SNF chromatin remodeling factor component BRG-1, and basal transcription factors TATA-binding protein (TBP) and TFIIB, as well as hyperacetylation of histones H3 and H4. These results highlight a critical role for NF-kappa B in bfl-1 transcription and point to the need for a complex and precise regulatory network to control bfl-1 expression. To our knowledge, this is the first demonstration of enhanceosome-mediated regulation of a cell death inhibitor.
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PMID:NF-kappa B-dependent assembly of an enhanceosome-like complex on the promoter region of apoptosis inhibitor Bfl-1/A1. 1266 76

Drug resistance as a result of overexpression of drug transporter genes presents a major obstacle in the treatment of cancers and infections. The molecular mechanisms underlying transcriptional up-regulation of drug transporter genes remains elusive. Employing Saccharomyces cerevisiae as a model, we analyzed here transcriptional regulation of the drug transporter gene PDR5 in a drug-resistant pdr1-3 strain. This mutant bears a gain-of-function mutation in PDR1, which encodes a transcriptional activator for PDR5. Similar to the well studied model gene GAL1, we provide evidence showing that PDR5 belongs to a group of genes whose transcription requires the Spt-Ada-Gcn5 acetyltransferase (SAGA) complex. We also show that the drugindependent PDR5 transcription is associated with enhanced promoter occupancy of coactivator complexes, including SAGA, Mediator, chromatin remodeling SWI/SNF complex, and TATA-binding protein. Analyzed by chromatin immunoprecipitations, loss of contacts between histones and DNA occurs at both promoter and coding sequences of PDR5. Consistently, micrococcal nuclease susceptibility analysis revealed altered chromatin structure at the promoter and coding sequences of PDR5. Our data provide molecular description of the changes associated with constitutive PDR5 transcription, and reveal the molecular mechanism underlying drug-independent transcriptional up-regulation of PDR5.
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PMID:On the mechanism of constitutive Pdr1 activator-mediated PDR5 transcription in Saccharomyces cerevisiae: evidence for enhanced recruitment of coactivators and altered nucleosome structures. 1529 7

We use chromatin immunoprecipitation assays to show that the Gcn5 histone acetyltransferase in SAGA is required for SWI/SNF association with the HO promoter and that binding of SWI/SNF and SAGA are interdependent. Previous results showed that SWI/SNF binding to HO was Gcn5 independent, but that work used a strain with a mutation in the Ash1 daughter-specific repressor of HO expression. Here, we show that Ash1 functions as a repressor that inhibits SWI/SNF binding and that Gcn5 is required to overcome Ash1 repression in mother cells to allow HO transcription. Thus, Gcn5 facilitates SWI/SNF binding by antagonizing Ash1. Similarly, a mutation in SIN3, like an ash1 mutation, allows both HO expression and SWI/SNF binding in the absence of Gcn5. Although Ash1 has recently been identified in a Sin3-Rpd3 complex, our genetic analysis shows that Ash1 and Sin3 have distinct functions in regulating HO. Analysis of mutant strains shows that SWI/SNF binding and HO expression are correlated and regulated by histone acetylation. The defect in HO expression caused by a mutant SWI/SNF with a Swi2(E834K) substitution can be partially suppressed by ash1 or spt3 mutation or by a gain-of-function V71E substitution in the TATA-binding protein (TBP). Spt3 inhibits TBP binding at HO, and genetic analysis suggests that Spt3 and TBP(V71E) act in the same pathway, distinct from that of Ash1. We have detected SWI/SNF binding at the HO TATA region, and our results suggest that SWI/SNF, either directly or indirectly, facilitates TBP binding at HO.
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PMID:SWI/SNF binding to the HO promoter requires histone acetylation and stimulates TATA-binding protein recruitment. 1670 63

While studying gene expression of the rudivirus SIRV1 in cells of its host, the hyperthermophilic crenarchaeon Sulfolobus, a novel archaeal transcriptional regulator was isolated. The 14 kDa protein, termed Sulfolobus transcription activator 1, Sta1, is encoded on the host chromosome. Its activating effect on transcription initiation from viral promoters was demonstrated in in vitro transcription experiments using a reconstituted host system containing the RNA polymerase, TATA-binding protein (TBP) and transcription factor B (TFB). Most pronounced activation was observed at low concentrations of either of the two transcription factors, TBP or TFB. Sta1 was able to bind viral promoters independently of any component of the host pre-initiation complex. Two binding sites were revealed by footprinting, one located in the core promoter region and the second approximately 30 bp upstream of it. Comparative modeling, NMR and circular dichroism of Sta1 indicated that the protein contained a winged helix-turn-helix motif, most probably involved in DNA binding. This strategy of the archaeal virus to co-opt a host cell regulator to promote transcription of its genes resembles eukaryal virus-host relationships.
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PMID:A novel archaeal regulatory protein, Sta1, activates transcription from viral promoters. 1697 99

The gene encoding ribonucleotide reductase 3 (RNR3) is strongly induced in response to DNA damage. Its expression is strictly dependent upon the TAF(II) subunits of TFIID, which are required for the recruitment of SWI/SNF and nucleosome remodeling. However, full activation of RNR3 also requires GCN5, the catalytic subunit of the SAGA histone acetyltransferase complex. Thus, RNR3 is dependent upon both TFIID and SAGA, two complexes that deliver TATA-binding protein (TBP) to promoters. Furthermore, unlike the majority of TFIID-dominated genes, RNR3 contains a consensus TATA-box, a feature of SAGA-regulated core promoters. Although a large fraction of the genome can be characterized as either TFIID- or SAGA-dominant, it is expected that many genes utilize both. The mechanism of activation and the relative contributions of SAGA and TFIID at genes regulated by both complexes have not been examined. Here we delineated the role of SAGA in the regulation of RNR3 and contrast it to that of TFIID. We find that SAGA components fulfill distinct functions in the regulation of RNR3. The core promoter of RNR3 is SAGA-dependent, and we provide evidence that SAGA, not TAF(II)s within TFIID, are largely responsible for TBP recruitment. This taken together with our previous work provides evidence that SAGA recruits TBP, whereas TFIID mediates chromatin remodeling. Thus, we described an unexpected shift in the division of labor between these two complexes and provide the first characterization of a gene that requires both SAGA and TFIID.
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PMID:Dissection of coactivator requirement at RNR3 reveals unexpected contributions from TFIID and SAGA. 1868 87

We previously reported that BRG1, an ATPase subunit of SWI/SNF chromatin remodelling complexes, is constitutively expressed and that the alternative ATPase subunit (BRM) is inducibly expressed through differentiation in mammalian cells. In the present study, the regulatory elements that confer constitutive expression on brg1 were explored. First, we analysed the promoter proximal region surrounding its transcriptional start site. Using computer-aided analysis, a TATA-less, GC-rich promoter containing four putative binding sites for Sp1/3 was predicted. One of the putative Sp1/3-binding sites (from -21 to -15 bp) overlapped with a putative YY1-binding site. A gel-shift assay showed that YY1 but not Sp1/3 bound to this sequence and that Sp3 but not Sp1 bound to the other three predicted binding sites. Furthermore, chromatin immunoprecipitation analysis showed that Sp3 and YY1 bound to the promoter region together with TATA-binding protein in vivo. In vivo and in vitro binding assays showed that Sp3 and YY1 interacted with each other. Together, these results suggest that Sp3 and YY1 recruit general transcription factors and facilitate the assembly of a preinitiation complex.
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PMID:Constitutive expression of the brg1 gene requires GC-boxes near to the transcriptional start site. 2114 56

Nasopharyngeal carcinoma (NPC) is notorious for its high invasiveness and metastatic ability. In this study, we identified a differential hypermethylated transcription repressor, Homeobox A2 (HOXA2), which may render NPC cells invasive and metastatic. Aberrant hypermethylation of HOXA2 led to low RNA expression in NPC tumors and cells. Addition of methylation inhibitor 5'Aza restored HOXA2 RNA expression in NPC cells. Methylated HOXA2 promoter reduces the binding affinity of the transcriptional co-activator p300, causing transcriptional repression of HOXA2. In NPC cells, re-expression of ectopic HOXA2 was correlated with decreased invasive ability and reduced metalloproteinase MMP-9 RNA and protein expression. Promoter, ChIP and DNA-pull down assays indicated that HOXA2 competes with the transcription activator, TATA-box binding protein (TBP) for a recognition sequence near the MMP-9 transcription start site, and suppresses MMP-9 transcription. Thus, HOXA2 acts as a suppressor or TBP-antagonist to inhibit MMP-9 expression; while methylation-mediated inactivation of HOXA2 in NPC derepresses MMP-9 production and increases invasion of NPC cells. In NPC plasma samples, increased plasma EBV copy number was correlated with increased in cell-free HOXA2 hypermethylation and elevated MMP-9 levels. Plasma EBV DNA and methylated cell-free HOXA2 can be used as biomarkers for monitoring NPC treatment.
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PMID:Aberrantly hypermethylated Homeobox A2 derepresses metalloproteinase-9 through TBP and promotes invasion in Nasopharyngeal carcinoma. 2424 17

In eukaryotes, transcription of protein encoding genes is initiated by the controlled deposition of the TATA-box binding protein TBP onto gene promoters, followed by the ordered assembly of a pre-initiation complex. The SAGA co-activator is a 19-subunit complex that stimulates transcription by the action of two chromatin-modifying enzymatic modules, a transcription activator binding module, and by delivering TBP. Recent cryo electron microscopy structures of yeast SAGA with bound nucleosome or TBP reveal the architecture of the different functional domains of the co-activator. An octamer of histone fold domains is found at the core of SAGA. This octamer, which deviates considerably from the symmetrical analogue forming the nucleosome, establishes a peripheral site for TBP binding where steric hindrance represses interaction with spurious DNA. The structures point to a mechanism for TBP delivery and release from SAGA that requires TFIIA and whose efficiency correlates with the affinity of DNA to TBP. These results provide a structural basis for understanding specific TBP delivery onto gene promoters and the role played by SAGA in regulating gene expression. The properties of the TBP delivery machine harboured by SAGA are compared with the TBP loading device present in the TFIID complex and show multiple similitudes.
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PMID:Architecture of the multi-functional SAGA complex and the molecular mechanism of holding TBP. 3294 70


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