Cdk5 levels oscillate during the neuronal cell cycle: Cdh1 Ubiquitination triggers proteosome-dependent degradation during S-phase

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	Cdk5 levels oscillate during the neuronal cell cycle: Cdh1 Ubiquitination triggers proteosome-dependent degradation during S-phase
	Zhang, J ; Li, Huifang ; Zhou, Tingwen ; Zhou, Jiechao ; Herrup, Karl ; Zhang J(张杰)
刊名	http://dx.doi.org/10.1074/jbc.M112.343152
	2012
关键词	Cell death Degradation Neurodegenerative diseases
英文摘要	When cell cycle re-activation occurs in post-mitotic neurons it places them at increased risk for death. The cell cycle/cell death association has been reported in many neurodegenerative diseases including Alzheimer disease (AD), yet the mechanisms by which a normal neuron suppresses the cycle remain largely unknown. Recently, our laboratory has shown that Cdk5 (cyclin-dependent kinase 5) is a key player in this protective function. When a neuron is under stress, Cdk5 is transported to the cytoplasm; this eliminates its cell cycle suppression activity and the neuron re-enters S-phase. In the current study we show that a similar principle applies during a normal cell cycle.Whena neuronal cell enters S phase, Cdk5 is transported to the cytoplasm where it is ubiquitinated by the E3 ligase APC-Cdh1. Ubiquitinated Cdk5 is then rapidly degraded by the proteasome. The ubiquitination site of Cdk5 appears to be in the p35 binding area; in the presence of high levels of p35, the ubiquitination of Cdk5 was blocked, and the degradation in S phase was attenuated. The data suggest an unsuspected role for Cdk5 during the progression of a normal cell cycle and offer new pharmaceutical targets for regulating neuronal cell cycling and cell death. 漏 2012 by The American Society for Biochemistry and Molecular Biology, Inc.
语种	英语
出版者	American Society for Biochemistry and Molecular Biology Inc.
内容类型	期刊论文
源URL	[http://dspace.xmu.edu.cn/handle/2288/93722]
专题	医学院－已发表论文
推荐引用方式 GB/T 7714	Zhang, J,Li, Huifang,Zhou, Tingwen,et al. Cdk5 levels oscillate during the neuronal cell cycle: Cdh1 Ubiquitination triggers proteosome-dependent degradation during S-phase[J]. http://dx.doi.org/10.1074/jbc.M112.343152,2012.
APA	Zhang, J,Li, Huifang,Zhou, Tingwen,Zhou, Jiechao,Herrup, Karl,&张杰.(2012).Cdk5 levels oscillate during the neuronal cell cycle: Cdh1 Ubiquitination triggers proteosome-dependent degradation during S-phase.http://dx.doi.org/10.1074/jbc.M112.343152.
MLA	Zhang, J,et al."Cdk5 levels oscillate during the neuronal cell cycle: Cdh1 Ubiquitination triggers proteosome-dependent degradation during S-phase".http://dx.doi.org/10.1074/jbc.M112.343152 (2012).