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)

Serum response factor (SRF), a transcription factor that binds to the serum response element (SRE) of the c-fos proto-oncogene, activates transcription of an SRE-containing reporter plasmid in vitro. We describe here preincubation experiments which indicate that SRF activates transcription by facilitating the formation of active preinitiation complexes. Full activation by SRF occurred if SRF was preincubated with the general transcription factors. However, if the general transcription factors were preincubated and SRF was added subsequently, only poor activation of transcription was observed. This suggests that SRF must be present during preinitiation complex formation and that this complex is refractory to activation if SRF is absent during its formation. We have fractionated the general transcription factors and found that only a highly purified fraction containing the TATA-binding factor TFIID (and other unidentified components) must be present during preincubation for maximal transcriptional induction by SRF. This supports a model in which SRF activates transcription by affecting the conformation of TFIID bound to the promoter. Also of interest was the finding that recombinant human TFIID expressed in bacteria cannot mediate SRF-activated transcription, although it does support basal transcription. These results suggest that SRF may affect TFIID via a cofactor or coactivator.
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PMID:Serum response factor affects preinitiation complex formation by TFIID in vitro. 190 74

Previous experiments have demonstrated that transcription of the human c-fos oncogene is activated through the action of the 289-amino acid adenovirus E1A gene product. In this study we have utilized a series of c-fos promoter deletion and substitution mutants to define regulatory sequences that allow the induction by E1A. Although the deletion of upstream promoter sequences has varying degrees of effect on overall promoter activity, these deletions retain inducibility by E1A. This includes the deletion of the serum response element and two elements that bind the ATF transcription factor. In fact, a c-fos promoter deleted to position -53, which leaves the TATA element but no other known functional element, retains inducibility, indicating a role for the TATA element in E1A control. Indeed, substitution of the c-fos TATA element (TATAA) with a TATA sequence from the simian virus 40 early promoter (TATTTAT) abolishes E1A inducibility; this promoter does retain responsiveness to cAMP induction, however, demonstrating that this TATTTAT substitution is functional. We conclude that the E1A-dependent activation of c-fos transcription is mediated through an effect on a TATA-binding protein that has specificity for the TATAA sequence.
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PMID:E1A-dependent trans-activation of the c-fos promoter requires the TATAA sequence. 213 44

Large T antigen (T antigen), the early gene product of simian virus 40 (SV40), is a potent transcriptional activator of both cellular and viral genes. Recently we have shown that T antigen is tightly associated with TFIID and, in this position, performs a TATA-binding protein (TBP)-associated factor (TAF)-like function. Based on this observation, we asked whether T antigen affected steps in preinitiation complex assembly. Using purified components in in vitro complex assembly assays, we found that T antigen specifically enhances the formation of the TBP-TFIIA complex on the TATA element. T antigen accomplishes this by increasing the rate of formation of the TBP-TFIIA complex on the TATA element and by stabilizing the complexes after they are formed on the promoter. In addition, DNA immunoprecipitation experiments indicate that T antigen is associated with the stabilized TBP-TFIIA complexes bound to the DNA. In this regard, it has previously been shown that T antigen interacts with TBP; in the present study, we show that T antigen also interacts with TFIIA in vitro. In testing the ability of T antigen to stabilize the TBP-TFIIA complex, we found that stabilization is highly sensitive to the specific sequence context of the TATA element. Previous studies showed that T antigen could activate simple promoters containing the TATA elements from the hsp70 and c-fos gene promoters but failed to significantly activate similar promoters containing the TATA elements from the promoters of the SV40 early and adenovirus E2a genes. We find that the ability to stabilize the TBP-TFIIA complex on the hsp70 and c-fos TATA elements, and not on the SV40 early and E2A TATA elements, correlates with the ability or inability to activate promoters containing these TATA elements.
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PMID:Simian virus 40 large T antigen stabilizes the TATA-binding protein-TFIIA complex on the TATA element. 963 77

The lack of direct targets for TATA-binding protein (TBP)-like factors (TLFs) confounds the understanding of their role in gene expression. Here we report that human TLF (also called TBP-related factor 2 [TRF2]) activates a number of different genes, including the neurofibromatosis type 1 (NF1) gene. The overexpression of TLF increases the amount of NF1 mRNA in cells. In vivo, TLF binds to and upregulates transcription from a fragment of the NF1 promoter. In vitro, purified TLF-TFIIA binds directly to the same NF1 promoter fragment that is required for TLF responsiveness in cells. Furthermore, targeted deletion of TLF in mice reduces NF1 levels. In contrast, TLF inhibits transcription driven by a fragment from the TATA-containing c-fos promoter by sequestering TFIIA. TBP affects the NF1 and c-fos promoters in a manner reciprocal to that of TLF, stimulating the c-fos promoter and inhibiting NF1 transcription. We conclude that TLF is a functional regulator of transcription with targets distinct from those of TBP.
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PMID:TATA-binding protein (TBP)-like factor (TLF) is a functional regulator of transcription: reciprocal regulation of the neurofibromatosis type 1 and c-fos genes by TLF/TRF2 and TBP. 1576 69

FOXM1c transactivates the c-myc promoter via the P1 and P2 TATA boxes using a new mechanism. Whereas the P1 TATA box TATAATGC requires its sequence context to be FOXM1c responsive, the P2 TATA box TATAAAAG alone is sufficient to confer FOXM1c responsiveness to any minimal promoter. FOXM1c transactivates by binding to the TATA box as well as directly to TATA-binding protein, transcription factor IIB and transcription factor IIA. This new transactivation mechanism is clearly distinguished from the function of FOXM1c as a conventional transcription factor. The central domain of FOXM1c functions as an essential domain for activation via the TATA box, but as an inhibitory domain (retinoblastoma protein-independent transrepression domain and retinoblastoma protein-recruiting negative regulatory domain) for transactivation via conventional FOXM1c-binding sites. Each promoter with the P2 TATA box TATAAAAG is postulated to be transactivated by FOXM1c. This was demonstrated for the promoters of c-fos, hsp70 and histone H2B/a. A database search revealed almost 300 probable FOXM1c target genes, many of which function in proliferation and tumorigenesis. Accordingly, dominant-negative FOXM1c proteins reduced cell growth approximately threefold, demonstrating a proliferation-stimulating function for wild-type FOXM1c.
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PMID:FOXM1c transactivates the human c-myc promoter directly via the two TATA boxes P1 and P2. 1696 35

The epidermal growth factor receptor (EGFR) family regulates essential biological processes. Various epithelial tumors are linked to EGFR overexpression or expression of variant forms, such as the EGFR1 variant, EGFRvIII. Perturbations in expression of the transcription initiation factor, TATA-binding protein (TBP), alter cellular growth properties. Here we demonstrate that EGFR1 and EGFRvIII, but not HER2, induce TBP expression at a transcriptional level through distinct mechanisms. EGFR1 enhances the phosphorylation and function of Elk-1, recruiting it to the TBP promoter. In contrast, EGFRvIII robustly induces c-jun expression, stimulating recruitment of c-fos/c-jun to an overlapping AP-1 site. Enhancing c-jun expression alone induces TBP promoter activity through the AP-1 site. To determine the underlying mechanism for differences in Elk-1 function and c-jun expression by these receptors, we inhibited the internalization of EGFR1. Persistent EGFR1 cell surface occupancy mimics EGFRvIII-mediated effects on Elk-1 and c-jun and switches the requirement of Elk-1 to AP-1 for TBP promoter induction. Together, these studies define a new molecular mechanism for the regulation of TBP expression. In addition, we identify distinct molecular targets of EGFR1 and EGFRvIII and demonstrate the importance of receptor internalization in distinguishing their specific functions.
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PMID:Epidermal growth factor receptor 1 (EGFR1) and its variant EGFRvIII regulate TATA-binding protein expression through distinct pathways. 1871 Sep 43