Graduate School of Biological Sciences, Nara Institute of Science and Technology, Nara, Japan.
FEBS Lett. 2010 Nov 19;584(22):4545-52. doi: 10.1016/j.febslet.2010.10.039. Epub 2010 Oct 26.
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.
COP9 信号小体（CSN）复合物对于哺乳动物细胞的增殖和存活至关重要，但尚不清楚 CSN 如何影响细胞周期。在这项研究中，使用 CRE-flox 系统生成了缺乏 CSN5/Jab1 的 MEF。在消除 CSN5/Jab1 后，MEF 停止增殖。挽救实验表明 CSN5/Jab1 的 JAMM 结构域是必需的。CSN5/Jab1 的消除增强了 cullin1 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 的消除在多个点抑制了细胞周期的进展，似乎启动了 p53 非依赖性衰老并增加了细胞的ploidy。因此，CSN5/Jab1 控制细胞周期的不同事件，防止衰老和内循环以及体细胞周期的正常进展。
