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Abstract：
Maintenance of genome integrity under the stressed condition is paramount for normal functioning of cells in the multicellular organisms. Cells are programmed to protect their genome through specialized adaptive mechanisms which will help decide their fate under stressed conditions. These mechanisms are the outcome of activation of the intricate circuitries that are regulated by the p53 master protein. In this paper, we provided a comprehensive review on p53, p53 homologues and their isoforms, including a description about the ubiquitin-proteasome system emphasizing its role in p53 regulation. p53 induced E3(Ub)-ligases are an integral part of the ubiquitin-proteasome system. This review outlines the roles of important E3(Ub)-ligases and their splice variants in maintaining cellular p53 protein homeostasis. It also covers up-to-date and relevant information on small molecule Mdm2 inhibitors originated from different organizations. The review ends with a discussion on future prospects and investigation directives for the development of next-generation modulators as p53 therapeutics.
摘要：
在应激条件下维持基因组完整性对于多细胞生物体中细胞的正常功能至关重要。细胞被编程为通过专门的适应性机制保护其基因组，这将有助于在压力条件下决定其命运。这些机制是由p53主蛋白调节的复杂电路激活的结果。在本文中,我们对p53、p53同源物及其亚型进行了全面的综述，包括关于泛素-蛋白酶体系统的描述，强调其在p53调节中的作用。p53诱导的E3（Ub）-连接酶是泛素-蛋白酶体系统的组成部分。这篇综述概述了重要的E3（Ub）-连接酶及其剪接变体在维持细胞p53蛋白稳态中的作用。它还涵盖了来自不同组织的小分子Mdm2抑制剂的最新和相关信息。该综述以关于下一代调节剂作为p53疗法的开发的未来前景和研究指令的讨论结束。
