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 Drosophila homeodomain protein Even-skipped (Eve) has previously been shown to function as a sequence-specific transcriptional repressor, and in vitro and in vivo experiments have shown that the protein can actively block basal transcription. However, the mechanism of repression is not known. Here, we present evidence establishing a direct interaction between Eve and the TATA-binding protein (TBP). Using cotransfection assays with minimal basal promoters whose activity can be enhanced by coexpression of TBP, we found that Eve could efficiently block, or squelch, this enhancement. Squelching did not require Eve DNA-binding sites on the reporter plasmids but was dependent on the presence of the Eve repression domain. Further support for an in vivo interaction between the Eve repression domain and TBP was derived from a two-hybrid-type assay with transfected cells. Evidence that Eve and TBP interact directly was provided by in vitro binding assays, which revealed a specific protein-protein interaction that required an intact Eve repression domain and the conserved C terminus of TBP. The Eve homeodomain was also required for these associations, suggesting that it may function in protein-protein interactions. We also show that a previously characterized artificial repression region behaves in a manner similar to that of the Eve repression domain, including its ability to squelch TBP-enhanced expression in vivo and to bind TBP specifically in vitro. Our results suggest a model for transcriptional repression that involves an interaction between Eve and TBP.
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PMID:The transcriptional repressor even-skipped interacts directly with TATA-binding protein. 765 19

The Drosophila homeodomain protein Even-skipped (Eve) is a well characterized transcriptional repressor. Here, we show that Eve's ability to function in vitro is negatively regulated by phosphorylation. DNA-binding activity was unaffected by phosphorylation, but phosphorylated Eve was unable to interact with the TATA-binding protein (TBP), a known target for repression. Unexpectedly, phosphorylation of the Eve N terminus, which is dispensable for repression and TBP binding, was necessary and sufficient to inactivate Eve. LiCl, which specifically inhibits glycogen synthase kinase-3 (GSK-3), reduced Eve phosphorylation in nuclear extract and blocked inhibition of repression. In addition, Eve was phosphorylated and inactivated by purified GSK-3 beta plus casein kinase II. Our results suggest a novel mechanism of transcriptional control involving phosphorylation-induced allosteric interference with a repressive protein-protein interaction.
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PMID:Allosteric regulation of even-skipped repression activity by phosphorylation. 1002 81

Four maternal systems are known to pattern the early Drosophila embryo. The key component of the anterior system is the homeodomain protein Bicoid (Bcd). Bcd needs the contribution of another anterior morphogen, Hunchback (Hb), to function properly: Bcd and Hb synergize to organize anterior development. A molecular mechanism for this synergy has been proposed to involve specific interactions of Bcd and Hb with TATA-binding protein-associated factors (TAFIIs) that are components of the general transcription machinery. Bcd contains three putative activation domains: a glutamine-rich region, which interacts in vitro with TAFII110; an alanine-rich domain, which targets TAFII60; and a C-terminal acidic region, which has an unknown role. We have generated flies carrying bcd transgenes lacking one or several of these domains to test their function in vivo. Surprisingly, a bcd transgene that lacks all three putative activation domains is able to rescue the bcdE1 null phenotype to viability. Moreover, the development of these embryos is not affected by the presence of dominant negative mutations in TAFII110 or TAFII60. This means that the interactions observed in vitro between Bcd and TAFII60 or TAFII110 aid transcriptional activation but are dispensable for normal development.
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PMID:Bicoid functions without its TATA-binding protein-associated factor interaction domains. 1020 Feb 84

Here the effect on DNA-mediated charge transport of binding by a variety of proteins is examined. DNA assemblies were constructed that contain a tethered rhodium intercalator, as photooxidant, as well as two 5'-GG-3' sites flanking the DNA-binding site for the different proteins. By monitoring the ratio of oxidative damage promoted at the guanine doublet situated distal to the protein-binding site versus that at the proximal site as a function of protein binding, the effects of binding the proteins on DNA-mediated charge transport were determined. Proteins examined included both the wild-type and mutant methyltransferase, M.HhaI, which are base-flipping enzymes, the restriction endonuclease R.PvuII, a TATA-binding protein, which kinks the DNA, and the transcription factor Antennapedia homeodomain protein, which binds DNA through a helix-turn-helix motif. In general, it was observed that yields of long-range oxidative damage correlate with protein-dependent alterations in DNA base stacking. Interactions that disturb the DNA pi-stack inhibit DNA charge transport. Alternatively, interactions that promote no helix distortion but, as a result of tight packing, may rigidify the pi-stack, serve instead to enhance the ability of the DNA base pairs to serve as a conduit for charge transport. Thus, protein binding to DNA modulates long-range charge transport both negatively and positively, depending upon the specific protein/DNA interactions in play. Long-range DNA charge transport and this modulation by protein binding may be important to consider physiologically.
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PMID:How different DNA-binding proteins affect long-range oxidative damage to DNA. 1133 Oct 21