Differential recognition of phosphorylated transactivation domains of p53 by different p300 domains
Differential recognition of phosphorylated transactivation domains of p53 by different p300 domains
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DOI：
10.1016/j.jmb.2007.11.082
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发表时间：
2008-02-08
影响因子：
5.6
通讯作者：
Roy, Siddhartha
中科院分区：
文献类型：
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作者：
Polley, Smarajit;Guha, Soumi;Roy, Siddhartha
组蛋白乙酰转移酶在将外源信号转导到转录的实际启动过程中起着至关重要的作用。通过p300与反式激活结构域不同残基上磷酸化的P53的相互作用，发生了大量的应激信号整合。这种相互作用如何激活不同的基因表达程序在很大程度上尚不清楚。P300至少包含五个已知与P53相互作用的结构域，但它们在转录调控中的作用尚不清楚。我们测量了不同磷酸化反式激活的结合亲和力。荧光各向异性分析p300的多个P53结合域。不同的P53磷酸化反式激活结构域与不同的p300结构域的结合亲和力相差几个数量级，这表明不同的翻译后修饰形式的P53可能通过不同的p300结构域发生相互作用。因此，不同的翻译后修饰的p53片段可能形成不同构型的转录启动复合体，导致不同的启动子和途径的激活。(C)2007爱思唯尔有限公司。保留所有权利。
Histone acetyltransferases form crucial links in transducing extrinsic signals to actual initiation of transcription. A multitude of stress signal integrations occur through the interaction of p300 with p53 phosphorylated at different residues of the transactivation domain. How such interactions activate different gene expression programs remains largely unknown. p300 contains at least five domains that are known to interact with p53, but their role in transcription regulation is not known. We measured the binding affinity of various phosphorylated transactivation. domains towards several p53 binding domains of p300 by fluorescence anisotropy. The binding affinities of different phosphorylated transactivation domains of p53 towards different domains of p300 vary by several orders of magnitude, indicating that interactions of different post-translationally modified forms of p53 may occur through different domains of p300. Thus, different post-translationally modified p53 fragments may form transcription-initiating complexes of different configurations, leading to the activation of different promoters and pathways. (C) 2007 Elsevier Ltd. All rights reserved.