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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >TFIIB dephosphorylation links transcription inhibition with the p53-dependent DNA damage response
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TFIIB dephosphorylation links transcription inhibition with the p53-dependent DNA damage response

机译：TFIIB去磷酸化将转录抑制与p53依赖性DNA损伤反应联系起来

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摘要

The general transcription factor IIB (TFIIB) plays a central role in both the assembly of the transcription complex at gene promoters and also in the events that lead to transcription initiation. TFIIB is phosphorylated at serine-65 at the promoters of several endogenous genes, and this modification is required to drive the formation of gene promoter-3' processing site contacts through the cleavage stimulation factor 3' (CstF 3')-processing complex. Here we demonstrate that TFIIB phosphorylation is dispensable for the transcription of genes activated by the p53 tumor suppressor. We find that the kinase activity of TFIIH is critical for the phosphorylation of TFIIB serine-65, but it is also dispensable for the transcriptional activation of p53-target genes. Moreover, we demonstrate that p53 directly interacts with CstF independent of TFIIB phosphorylation, providing an alternative route to the recruitment of 3 -processing complexes to the gene promoter. Finally, we show that DNA damage leads to a reduction in the level of phospho-ser65 TFIIB that leaves the p53 transcriptional response intact, but attenuates transcription at other genes. Our data reveal a mode of phospho-TFIIB-independent transcriptional regulation that prioritizes the transcription of p53-target genes during cellular stress.
机译：通用转录因子IIB（TFIIB）在基因启动子处的转录复合体组装以及导致转录起始的事件中都起着核心作用。 TFIIB在几个内源基因的启动子处的65位丝氨酸处被磷酸化，并且需要这种修饰来驱动基因启动子3'加工位点通过裂解刺激因子3'（CstF 3'）-加工复合物的形成。在这里，我们证明了TFIIB磷酸化对于p53肿瘤抑制因子激活的基因的转录是可有可无的。我们发现，TFIIH的激酶活性对于TFIIB丝氨酸65的磷酸化至关重要，但对于p53靶基因的转录激活也是必不可少的。此外，我们证明p53直接与CstF相互作用而独立于TFIIB磷酸化，提供了将3种加工复合物募集到基因启动子的替代途径。最后，我们表明DNA损伤导致磷酸化Ser65 TFIIB的水平降低，从而使p53转录反应保持完整，但减弱其他基因的转录。我们的数据揭示了一种磷-TFIIB独立的转录调控模式，该模式在细胞应激过程中优先处理p53-靶基因的转录。

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    Jayasha Shandilya; Yuming Wang; Stefan G. E. Roberts;

  • 作者单位

    Department of Biological Sciences, University at Buffalo, The State University of New York, Buffalo, NY 14260;

    Department of Biological Sciences, University at Buffalo, The State University of New York, Buffalo, NY 14260 Cancer Research UK, London Research Institute, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, United Kingdom;

    Department of Biological Sciences, University at Buffalo, The State University of New York, Buffalo, NY 14260;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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  • 正文语种 eng
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