The emerging role of deubiquitinating enzymes in genomic integrity, diseases, and therapeutics.
The emerging role of deubiquitinating enzymes in genomic integrity, diseases, and therapeutics.
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DOI：
10.1186/s13578-016-0127-1
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发表时间：
2016
影响因子：
7.5
通讯作者：
Wan Y
中科院分区：
文献类型：
--
作者：
He M;Zhou Z;Shah AA;Zou H;Tao J;Chen Q;Wan Y
在DNA损伤信号的作用下，信号蛋白上的泛素单链或多聚链的加入被认为是促进DNA损伤位点识别、检查点功能激活、终止和检查点反应以及DNA修复蛋白募集的关键事件。尽管有泛素修饰剂，但通过去泛素化酶（DUBs）从功能蛋白质中去除泛素在协调DNA损伤反应以及DNA修复过程中起着重要作用。去调节的泛素化和去泛素化可能导致基因组不稳定，进而导致肿瘤发生。最近的TCGA研究进一步揭示了DUB改变中的突变与各种类型肿瘤之间的联系。此外，基于DUBs的新兴药物设计为抗癌治疗提供了新的途径。本文综述了DUBs的去泛素化作用和特异性，以及DUBs在泛素介导的DNA损伤反应和DNA损伤修复中的作用。我们将进一步讨论DUBs参与肿瘤的发生，以及作为一种新的抗癌治疗策略的去泛素化的拦截。
The addition of mono-ubiquitin or poly-ubiquitin chain to signaling proteins in response to DNA damage signal is thought to be a critical event that facilitates the recognition of DNA damage lesion site, the activation of checkpoint function, termination and checkpoint response and the recruitment of DNA repair proteins. Despite the ubiquitin modifiers, removal of ubiquitin from the functional proteins by the deubiquitinating enzymes (DUBs) plays an important role in orchestrating DNA damage response as well as DNA repair processes. Deregulated ubiquitination and deubiquitination could lead to genome instability that in turn causes tumorigenesis. Recent TCGA study has further revealed the connection between mutations in alteration of DUBs and various types of tumors. In addition, emerging drug design based on DUBs provides a new avenue for anti-cancer therapy. In this review, we will summarize the role of deubiquitination and specificity of DUBs, and highlight the recent discoveries of DUBs in the modulation of ubiquitin-mediated DNA damage response and DNA damage repair. We will furthermore discuss the DUBs involved in the tumorigenesis as well as interception of deubiquitination as a novel strategy for anti-cancer therapy.
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影响因子：
11.2
作者：
Chernikova SB;Razorenova OV;Higgins JP;Sishc BJ;Nicolau M;Dorth JA;Chernikova DA;Kwok S;Brooks JD;Bailey SM;Game JC;Brown JM
通讯作者：
Brown JM
影响因子：
4.3
作者：
Aressy, Bernadette;Jullien, Denis;Ducommun, Bernard
通讯作者：
Ducommun, Bernard
影响因子：
12.4
作者：
Bohgaki, M.;Hakem, A.;Hakem, R.
通讯作者：
Hakem, R.
影响因子：
11.4
作者：
Cooper, Eric M.;Cutcliffe, Colleen;Cohen, Robert E.
通讯作者：
Cohen, Robert E.
影响因子：
16
作者：
Chen X;Walters KJ
通讯作者：
Walters KJ