p53-mediated repression of nuclear factor-kappaB RelA via the transcriptional integrator p300.
p53-mediated repression of nuclear factor-kappaB RelA via the transcriptional integrator p300.
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发表时间：
1998-10
期刊：
影响因子：
11.2
通讯作者：
R. Ravi;B. Mookerjee;Y. V. Hensbergen;Gauri C. Bedi;Antonio Giordano;W. El-Deiry;E. Fuchs;A. Bedi
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文献类型：
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作者：
R. Ravi;B. Mookerjee;Y. V. Hensbergen;Gauri C. Bedi;Antonio Giordano;W. El-Deiry;E. Fuchs;A. Bedi
P53抑癌基因在参与细胞应激反应的靶基因的转录调控中起着重要作用。依赖于p53的反式激活和反式转录需要它与p300/CBP相互作用，p300/CBP是一种共激活因子，也与核因子-kappaB的relA亚单位相互作用。我们发现，P53抑制RelA依赖的反式激活，而不改变relA的表达或诱导的kappaB-DNA结合。P53介导的对relA的抑制可以通过p300的过表达来缓解，而由p53缺失导致的relA活性的增加可以被与relA结合的反式激活结构域缺陷的p300片段或IkappaBα的跨显性突变体所抵消。我们的结果表明，P53可以调节多种依赖kappaB的细胞反应。
The p53 tumor suppressor gene plays an instrumental role in transcriptional regulation of target genes involved in cellular stress responses. p53-dependent transactivation and transrepression require its interaction with p300/CBP, a coactivator that also interacts with the RelA subunit of nuclear factor-kappaB. We find that p53 inhibits RelA-dependent transactivation without altering RelA expression or inducible kappaB-DNA binding. p53-mediated repression of RelA is relieved by p300 overexpression and the increased RelA activity conferred by p53-deficiency is counteracted by either transactivation domain-deficient p300 fragments that bind RelA or a transdominant mutant of IkappaB alpha. Our results suggest that p53 can regulate diverse kappaB-dependent cellular responses.