CSN5/Jab1 controls multiple events in the mammalian cell cycle
CSN5/Jab1 controls multiple events in the mammalian cell cycle
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DOI：
10.1016/j.febslet.2010.10.039
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发表时间：
2010-11-19
期刊：
影响因子：
3.5
通讯作者：
Kato, Jun-ya
中科院分区：
文献类型：
--
作者：
Yoshida, Akihiro;Yoneda-Kato, Noriko;Kato, Jun-ya
COP9 信号体 (CSN) 复合物对于哺乳动物细胞增殖和存活至关重要，但尚不清楚 CSN 如何影响细胞周期。在本研究中，使用 CRE-flox 系统生成缺乏 CSN5/Jab1 的 MEF。消除 CSN5/Jab1 后，MEF 停止增殖。拯救实验表明 CSN5/Jab1 的 JAMM 结构域是必需的。 CSN5/Jab1 消除增强了 cullins 1 和 4 的 neddylation，并改变了许多因子的表达，包括细胞周期蛋白 E 和 p53。 CSN5/Jab1 消除在多个点抑制细胞周期的进展，似乎启动了不依赖于 p53 的衰老并增加了细胞的倍性。因此，CSN5/Jab1 控制细胞周期的不同事件，防止衰老和内周期以及体细胞周期的正常进展。 结构化摘要：MINT-8046253：Csn1 (uniprotkb:Q99LD4) 与 Csn5 (uniprotkb:O35864)、Csn8 物理相互作用 (MI:0914) (uniprotkb:Q8VBV7)、Csn3 (uniprotkb:O88543)、Csn7b (uniprotkb:Q8BV13) 和 Csn6 (uniprotkb:O88545)，通过抗诱饵共免疫沉淀 (MI: 0006) (C) 2010 年欧洲生化协会联合会。由 Elsevier B.V 出版。保留所有权利。
The COP9 signalosome (CSN) complex is critical for mammalian cell proliferation and survival, but it is not known how the CSN affects the cell cycle. In this study, MEFs lacking CSN5/Jab1 were generated using a CRE-flox system. MEFs ceased to proliferate upon elimination of CSN5/Jab1. Rescue experiments indicated that the JAMM domain of CSN5/Jab1 was essential. CSN5/Jab1-elimination enhanced the neddylation of cullins 1 and 4 and altered the expression of many factors including cyclin E and p53. CSN5/Jab1-elimination inhibited progression of the cell cycle at multiple points, seemed to initiate p53-independent senescence and increased the ploidy of cells. Thus, CSN5/Jab1 controls different events of the cell cycle, preventing senescence and endocycle as well as the proper progression of the somatic cell cycle.Structured summary: MINT-8046253: Csn1 (uniprotkb:Q99LD4) physically interacts (MI:0914) with Csn5 (uniprotkb:O35864), Csn8 (uniprotkb:Q8VBV7), Csn3 (uniprotkb:O88543), Csn7b (uniprotkb:Q8BV13) and Csn6 (uniprotkb:O88545) by anti bait coimmunoprecipitation (MI: 0006) (C) 2010 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.