Biomedical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, UK.
Cold Spring Harb Perspect Biol. 2009 Dec;1(6):a000950. doi: 10.1101/cshperspect.a000950. Epub 2009 Oct 28.
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.
p53 蛋白可被多达 50 种不同的翻译后修饰。这些修饰中的许多都是在应对遗传毒性或非遗传毒性应激时发生的，并且表现出相互依存性，即一种或多种修饰可以引发随后的事件。这种相互依存的性质表明存在一种途径，该途径通过多个协同事件起作用，而不是单个、孤立的修饰具有不同的功能。这一概念得到了最近研究的支持，这些研究详细说明了各种修饰如何以协同方式介导精确的蛋白质-蛋白质相互作用，这可能解释了为什么表达一种或几种修饰位点被取代的 p53 蛋白的 knockin 小鼠通常对 p53 功能只有微小的影响。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，即修饰对 p53 功能的影响是通过集体和综合事件来实现的。
