Role of p97/VCP (Cdc48) in genome stability.
Role of p97/VCP (Cdc48) in genome stability.
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DOI：
10.3389/fgene.2013.00060
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发表时间：
2013
影响因子：
3.7
通讯作者：
Ramadan K
中科院分区：
文献类型：
--
作者：
Vaz B;Halder S;Ramadan K
泛素依赖性分子伴侣蛋白p97，又称含valosin-containing protein （VCP）或Cdc48，是一种参与蛋白质周转和降解的AAA atp酶。p97将其自身的atp酶水解转化为来自不同细胞位置和途径的无数泛素化底物的重塑活性。通过这种方式，p97介导从细胞区室或蛋白复合物中提取目标蛋白。从各种细胞环境中提取依赖p97的蛋白维持细胞蛋白稳态。近年来，从染色质中提取p97依赖性蛋白已成为维持基因组稳定的重要进化保守过程。p97分离酶活性的失活导致染色质上泛素化底物的积累，从而导致蛋白质诱导的染色质应激（PICHROS）。PICHROS直接影响多种DNA代谢过程，包括复制、损伤反应、有丝分裂和转录，导致基因毒性应激和基因组不稳定。通过总结和批判性评估p97在各种染色质相关蛋白降解过程中的功能的最新数据，我们提出将p97作为基因组看守者。
Ubiquitin-dependent molecular chaperone p97, also known as valosin-containing protein (VCP) or Cdc48, is an AAA ATPase involved in protein turnover and degradation. p97 converts its own ATPase hydrolysis into remodeling activity on a myriad of ubiquitinated substrates from different cellular locations and pathways. In this way, p97 mediates extraction of targeted protein from cellular compartments or protein complexes. p97-dependent protein extraction from various cellular environments maintains cellular protein homeostasis. In recent years, p97-dependent protein extraction from chromatin has emerged as an essential evolutionarily conserved process for maintaining genome stability. Inactivation of p97 segregase activity leads to accumulation of ubiquitinated substrates on chromatin, consequently leading to protein-induced chromatin stress (PICHROS). PICHROS directly and negatively affects multiple DNA metabolic processes, including replication, damage responses, mitosis, and transcription, leading to genotoxic stress and genome instability. By summarizing and critically evaluating recent data on p97 function in various chromatin-associated protein degradation processes, we propose establishing p97 as a genome caretaker.
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