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

The retinoblastoma tumor suppressor protein has been shown to bind directly and inhibit a transcriptionally-important amino-terminal kinase domain of TATA-binding protein-associated factor TAFII250. Cyclin D1 also is able to associate with the amino terminus of TAFII250 in a region very similar to or overlapping the Rb-binding site. In this study, we have examined whether cyclin D1 affects the functional interaction between Rb and TAFII250. We observed that when cyclin D1 is coincubated with Rb and TAFII250, the ability of Rb to inhibit TAFII250 kinase activity is effectively blocked. However, cyclin D1 by itself has no apparent effect on TAFII250 kinase activity. We further found that the Rb-related protein p107 can inhibit TAFII250 kinase activity, and this inhibition is likewise alleviated by cyclin D1. Cyclin D1 prevents the kinase-inhibitory effect of an Rb mutant unable to bind to D-type cyclins, indicating that it is acting through its association with TAFII250 and not with Rb. However, we found no evidence of TAFII250-binding competition between Rb and cyclin D1 in vitro. The adenovirus E1A protein, which also binds to both Rb and TAFII250, exhibited a suppressive effect on Rb-mediated kinase inhibition similar to that seen with cyclin D1. Our results suggest a novel means by which cyclin D1 may be able to independently regulate the activity of Rb.
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PMID:Cyclin D1 suppresses retinoblastoma protein-mediated inhibition of TAFII250 kinase activity. 1112 56

Transcription factor IIA (TFIIA) is a positive acting general factor that contacts the TATA-binding protein (TBP) and mediates an activator-induced conformational change in the transcription factor IID (TFIID) complex. Previously, we have found that phosphorylation of yeast TFIIA stimulates TFIIA.TBP.TATA complex formation and transcription activation in vivo. We now show that human TFIIA is phosphorylated in vivo on serine residues that are partially conserved between yeast and human TFIIA large subunits. Alanine substitution mutation of serine residues 316 and 321 in TFIIA alphabeta reduced TFIIA phosphorylation significantly in vivo. Additional alanine substitutions at serines 280 and 281 reduced phosphorylation to undetectable levels. Mutation of all four serine residues reduced the ability of TFIIA to stimulate transcription in transient transfection assays with various activators and promoters, indicating that TFIIA phosphorylation is required globally for optimal function. In vitro, holo-TFIID and TBP-associated factor 250 (TAF(II)250) phosphorylated TFIIA on the beta subunit. Mutation of the four serines required for in vivo phosphorylation eliminated TFIID and TAF(II)250 phosphorylation in vitro. The NH(2)-terminal kinase domain of TAF(II)250 was sufficient for TFIIA phosphorylation, and this activity was inhibited by full-length retinoblastoma protein but not by a retinoblastoma protein mutant defective for TAF(II)250 interaction or tumor suppressor activity. TFIIA phosphorylation had little effect on the TFIIA.TBP.TATA complex in electrophoretic mobility shift assay. However, phosphorylation of TFIIA containing a gamma subunit Y65A mutation strongly stimulated TFIIA.TBP.TATA complex formation. TFIIA-gammaY65A is defective for binding to the beta-sheet domain of TBP identified in the crystal structure. These results suggest that TFIIA phosphorylation is important for strengthening the TFIIA.TBP contact or creating a second contact between TFIIA and TBP that was not visible in the crystal structure.
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PMID:Taf(II) 250 phosphorylates human transcription factor IIA on serine residues important for TBP binding and transcription activity. 1127 96

Retinoblastoma-binding protein 2 (Rbp2) was originally identified as a retinoblastoma protein (RB) pocket domain-binding protein. Although Rbp2 has been shown to interact with RB, p107, TATA-binding protein, and T-cell oncogene rhombotin-2, the physiological function of Rbp2 remains unclear. Here we demonstrate that Rbp2 not only binds to nuclear receptors (NRs) but also enhances the transcription mediated by them. Rbp2 interacts with the DNA-binding domains of NRs and potentiates NR-mediated transcription in an AF-2-dependent manner. Both the N-terminal and C-terminal domains of Rbp2 are critical for the transactivation activity of Rbp2 on NRs. The C terminus is the NR-interacting region. In addition, RB functions in maximizing the effect of Rbp2 on the transcription by NRs. These results suggest that Rbp2 is a coregulator of NRs and define a potential role for Rbp2 in NR-mediated transcription.
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PMID:Retinoblastoma-binding protein 2 (Rbp2) potentiates nuclear hormone receptor-mediated transcription. 1135 60

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


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