Transcriptional repression by p53 involves molecular interactions distinct from those with the TATA box binding protein
Transcriptional repression by p53 involves molecular interactions distinct from those with the TATA box binding protein
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DOI：
10.1093/nar/24.21.4281
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发表时间：
1996-11-01
影响因子：
14.9
通讯作者：
Prives, C
中科院分区：
文献类型：
--
作者：
Farmer, G;Friedlander, P;Prives, C
除了作为DNA结合依赖性转录激活因子的作用外，已经报道p53抑制多种缺乏p53结合位点的启动子。最近的研究数据表明，这种活性是通过p53和TATA盒结合蛋白（TBP）之间的相互作用介导的。为了研究这种相互作用在体内的功能相关性，我们在果蝇Schneider细胞中进行了瞬时转染试验，发现野生型p53抑制由GAL 4-VP 16、GAL 4-ftzQ或Sp1激活的含TATA盒启动子的表达，但不抑制起始子（Inr）的表达，突变体p53（（His 175）），DNA结合和转录激活缺陷的p53也抑制由Sp1激活的TATA依赖性转录，然而，p53不能抑制由TBP过表达激活的基础TATA启动子。此外，TBP的过表达未能挽救p53介导的对活化转录的抑制，并且其N-末端TBP相互作用结构域完整的p53突变体，但在转录激活和与TBP相关因子（TAF）的结合方面有缺陷，在转录抑制方面同样有缺陷，这些数据表明，p53-TBP相互作用不足以通过p53进行转录抑制，并且抑制涉及p53和其他因子之间的相互作用，如TAF，它们是激活转录而非基础转录所需的。我们认为p53介导的抑制是由于抑制了一种限制TATA启动子而不是含Inr启动子激活转录的因子。
In addition to serving a role as a DNA binding-dependent transcriptional activator, p53 has been reported to repress a variety of promoters that lack p53 binding sites, Data from recent studies have suggested that this activity is mediated via an interaction between p53 and the TATA box binding protein (TBP), To investigate the functional relevance of this interaction in vivo, we have performed transient transfection assays in Drosophila Schneider cells, Wild-type p53 was found to repress expression from TATA box- but not initiator (Inr)-containing promoters activated by GAL4-VP16, GAL4-ftzQ or Sp1, A mutant p53((His175)), defective in DNA binding and transcriptional activation, also inhibited TATA-dependent transcription activated by Sp1, However, p53 was unable to repress a basal TATA promoter stimulated by overexpression of TBP, Furthermore, overexpression of TBP failed to rescue the p53-mediated repression of activated transcription and a p53 mutant with its N-terminal TBP interaction domain intact, but defective in transcriptional activation and binding to TBP-associated factors (TAFs), was similarly defective in transcriptional repression, These data suggest that a p53-TBP interaction is not sufficient for transcriptional repression by p53 and that repression involves an interaction between p53 and other factors, such as TAFs, that are required for activated but not basal transcription, We suggest that p53-mediated repression results from squelching of a factor limiting for activated transcription from TATA- but not Inr-containing promoters.