机构：[1]Department of Obstetrics and Gynecology, West China Second University Hospital, Key Laboratory of Birth Defects and Related Diseases of Women andChildren, Ministry of Education, College of Life Sciences, State Key Laboratory of Biotherapy and Collaborative Innovation Center of Biotherapy, SichuanUniversity, 610041 Chengdu, China[2]Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, 610041Chengdu, China[3]Department of Pathology, Hospital 363 of Aviation Industry Corporation of China, 610041 Chengdu, China[4]Department of Pediatrics,West China Second University Hospital, Sichuan University, 610041 Chengdu, China[5]Center of Growth, Metabolism and Aging, Key Laboratory of Bio-Resource and Eco-Environment, Ministry of Education, College of Life Sciences, Sichuan University, 610064 Chengdu, China[6]Sichuan Cunde Therapeutics,610093 Chengdu, China[7]Key Laboratory of Stem Cell Biology, Chinese Academy of Sciences Center for Excellence in Molecular Cell Science, Institute ofHealth Sciences, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, 200031 Shanghai, China
The assembly of prereplicative complex (pre-RC) during G1 phase must be tightly controlled to sustain cell proliferation and maintain genomic stability. Mechanisms to prevent pre-RC formation in G2/M and S phases are well appreciated, whereas how cells ensure efficient pre-RC assembly during G1 is less clear. Here we report that cyclin K regulates pre-RC formation. We find that cyclin K expression positively correlates with cell proliferation, and knockdown of cyclin K or its cognate kinase CDK12 prevents the assembly of pre-RC in G1 phase. Mechanistically we uncover that cyclin K promotes pre-RC assembly by restricting cyclin E1 activity in G1. We identify a cyclin K-dependent, novel phosphorylation site in cyclin E1 that disrupts its interaction with CDK2. Importantly, this antagonistic relationship is largely recapitulated in cyclin E1-overexpressing tumors. We discuss the implications of our findings in light of recent reports linking cyclin K and CDK12 to human tumorigenesis.
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外文
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出版当年[2018]版：
大类|2 区综合性期刊
小类|2 区综合性期刊
最新[2023]版：
大类|1 区综合性期刊
小类|1 区综合性期刊
第一作者：
第一作者机构：[1]Department of Obstetrics and Gynecology, West China Second University Hospital, Key Laboratory of Birth Defects and Related Diseases of Women andChildren, Ministry of Education, College of Life Sciences, State Key Laboratory of Biotherapy and Collaborative Innovation Center of Biotherapy, SichuanUniversity, 610041 Chengdu, China
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推荐引用方式(GB/T 7714)：
Lei Tingjun,Zhang Peixuan,Zhang Xudong,et al.Cyclin K regulates prereplicative complex assembly to promote mammalian cell proliferation.[J].Nature communications.2018,9(1):1876.doi:10.1038/s41467-018-04258-w.
APA：
Lei Tingjun,Zhang Peixuan,Zhang Xudong,Xiao Xue,Zhang Jingli...&Li Qintong.(2018).Cyclin K regulates prereplicative complex assembly to promote mammalian cell proliferation..Nature communications,9,(1)
MLA：
Lei Tingjun,et al."Cyclin K regulates prereplicative complex assembly to promote mammalian cell proliferation.".Nature communications 9..1(2018):1876
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