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)

The results presented describe the effects of various spectator ligands, attached to a platinum 1,2-intrastand d(GpG) cross-link in duplex DNA, on the binding of high mobility group box (HMGB) domains and the TATA-binding protein (TBP). In addition to cisplatin-modified DNA, 15-base pair DNA probes modified by [Pt(1R,2R-diaminocyclohexane)](2+), cis-[Pt(NH(3))(cyclohexylamine)](2+), [Pt(ethylenediamine)](2+), cis-[Pt(NH(3))(cyclobutylamine)](2+), and cis-[Pt(NH(3))(2-picoline)](2+) were examined. Electrophoretic mobility shift assays show that both the A and B domains of HMGB1 as well as TBP discriminate between different platinum-DNA adducts. HMGB1 domain A is the most sensitive to the nature of the spectator ligands on platinum. The effect of the spectator ligands on protein binding also depends highly on the base pairs flanking the platinated d(GpG) site. Double-stranded oligonucleotides containing the AG*G*C sequence, where the asterisks denote the sites of platination, with different spectator ligands are only moderately discriminated by the HMGB proteins and TBP, but the recognition of dsTG*G*A is highly dependent on the ligands. The effects of HMGB1 overexpression in a BG-1 ovarian cancer cell line, induced by steroid hormones, on the sensitivity of cells treated with [Pt(1R,2R-diaminocyclohexane)Cl(2)] and cis-[Pt(NH(3))(cyclohexylamine)Cl(2)] were also examined. The results suggest that HMGB1 protein levels influence the cellular processing of cis-[Pt(NH(3))- (cyclohexylamine)](2+), but not [Pt((1R,2R)-diaminocyclohexane)](2+), DNA lesions. This result is consistent with the observed binding of HMGB1a to platinum-modified dsTG*G*A probes but not with the binding affinity of HMGB1a and HMGB1 to platinum-damaged dsAG*G*C oligonucleotides. These experiments reinforce the importance of sequence context in platinum-DNA lesion recognition by cellular proteins.
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PMID:Effects of spectator ligands on the specific recognition of intrastrand platinum-DNA cross-links by high mobility group box and TATA-binding proteins. 1151 69

The TATA-binding protein (TBP) recognizes the TATA box element of transcriptional promoters and recruits other initiation factors. This essential protein binds selectively to cisplatin-damaged DNA. Electrophoretic mobility shift assays were performed to study the kinetics of TBP binding both to the TATA box and to cisplatin-damaged DNA in different sequence contexts. TBP binds with high affinity (K(d) = 0.3 nm) to DNA containing site-specific cisplatin 1,2-intrastrand d(GpG) cross-links. The k(on) and k(off) values for the formation of these TBP complexes are 1-3 x 10(5) m(-1) s(-1) and approximately 1-5 x 10(-4) s(-1), respectively, similar to the corresponding values for the formation of a TBP-TATA box complex. In electrophoretic mobility shift assay competition assays, cisplatin-damaged DNA extensively sequesters TBP from its natural binding site, the TATA box. Nine DNA probes were prepared to determine the flanking sequence dependence of TBP binding to cisplatin-modified DNA. TBP clearly displays sequence context selectivity for platinated DNA, very similar to but not as dramatic as that of the high mobility group protein HMGB1. When TBP was added to an in vitro nucleotide excision repair assay, it specifically shielded cisplatin-modified 1,2-(GpG) intrastrand cross-links from repair. These results indicate that TBP is likely to be a key protein in mediating the cytotoxicity of cisplatin.
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PMID:Kinetic studies of the TATA-binding protein interaction with cisplatin-modified DNA. 1156 87

Successful assembly of the transcriptional preinitiation complex (PIC) is prerequisite to transcriptional initiation. At each stage of PIC assembly, regulation may occur as repressors and activators compete with and influence the incorporation of general transcription factors (GTFs). Both TFIIA and HMGB1 bind individually to the TATA-binding protein (TBP) to increase the rate of binding and to stabilize TBP binding to the TATA element. The competitive binding between these two cofactors for TBP/TATA was examined to show that TFIIA binds preferentially to TBP and inhibits HMGB1 binding. TFIIA can also readily dissociate HMGB1 from the preestablished HMGB1/TBP/TATA complex. This suggests that TFIIA and HMGB1 may bind to the same or overlapping sites on TBP and/or compete for similar DNA sites that are 5' to the TATA element. In addition, EMSA studies show that adenovirus E1A(13S) oncoprotein is unable to disrupt either the preestablished TFIIA/TBP/TATA or TFIIA/TFIIB/TBP/TATA complexes, but does inhibit complex formation when all transcription factors were simultaneously added. The inhibitory effect of E1A(13S) on the assembly of the PIC is overcome when excess TBP is added back in the reaction, while addition of either excess TFIIA or TFIIB were ineffective. This shows that the main target for E1A(13S) is free TBP and emphasizes the primary competition between E1A and the TATA-element for unbound TBP. This may be the principal point, if not the only point, at which E1A can target TBP to exert its inhibitory effect. This work, coupled with previous findings in our laboratory, indicates that TFIIA is much more effective than TFIIB in reversing the inhibitory effect of HMGB1 binding in the early stages of PIC assembly, which is consistent with the in vitro transcription results.
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PMID:TFIIA abrogates the effects of inhibition by HMGB1 but not E1A during the early stages of assembly of the transcriptional preinitiation complex. 1281 28