Posttranslational Modification of p53: Cooperative Integrators of Function
Posttranslational Modification of p53: Cooperative Integrators of Function
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DOI：
10.1101/cshperspect.a000950
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发表时间：
2009-12-01
影响因子：
7.2
通讯作者：
Anderson, Carl W.
中科院分区：
文献类型：
--
作者：
Meek, David W.;Anderson, Carl W.
p53蛋白被多达50个单独的翻译后修饰。其中许多是对遗传毒性或非遗传毒性胁迫的反应，并表现出相互依赖性，因此一种或多种修饰可以成为后续事件的核心。这种相互依赖的本质表明，这种途径是通过多个合作事件来运作的，而不是通过单独的、孤立的修改来实现不同的功能。这一概念得到了最近的研究的支持，这些研究提供了各种修饰如何以合作的方式介导精确的蛋白质-蛋白质相互作用的精细细节，这可能解释了为什么在一个或几个修饰位点上表达p53蛋白的敲入小鼠通常只对p53功能产生微妙的影响。本文重点介绍了最近令人兴奋的进展，并提出了这样一种观点，即p53功能的改变是通过集体和综合事件实现的。
The p53 protein is modified by as many as 50 individual posttranslational modifications. Many of these occur in response to genotoxic or nongenotoxic stresses and show interdependence, such that one or more modifications can nucleate subsequent events. This interdependent nature suggests a pathway that operates through multiple cooperative events as opposed to distinct functions for individual, isolated modifications. This concept, supported by recent investigations, which provide exquisite detail as to how various modifications mediate precise protein-protein interactions in a cooperative manner, may explain why knockin mice expressing p53 proteins substituted at one or just a few sites of modification typically show only subtle effects on p53 function. The present article focuses on recent, exciting progress and develops the idea that the impact of modification on p53 function is achieved through collective and integrated events.