Cyclin A2/cyclin-dependent kinase 1-dependent phosphorylation of Top2a is required for S phase entry during retinal development in zebrafish  

作　　者：Miaomiao Jin Jingyu Li Ruikun Hu Baijie Xu Guanliang Huang Weilai Huang Bo Chen Jie He Ying Cao 

机构地区：[1]Department of Clinical Laboratory Medicine of Shanghai Tenth People’s Hospital,Tongji University School of Life Sciences and Technology,Shanghai 200092,China [2]Institute of Neuroscience,State Key Laboratory of Neuroscience,CAS Center for Excellence in Brain Science and Intelligence Technology,Chinese Academy of Sciences,Shanghai 200031,China [3]University of Chinese Academy of Sciences,Beijing 100049,China

出　　处：《Journal of Genetics and Genomics》2021年第1期63-74,共12页遗传学报（英文版）

基　　金：supported by grants from the National Key Research and Development Program of China (2017YFA0104600);the National Natural Science Foundation of China (31970767, 31771597 and 31571515);the National Basic Research Program of China (973 Program 2012CB966601 and 2013CB945300);the Ministry of Science and Technology of the People’s Republic of China (2011DFB30010)。

摘　　要：Cyclin-dependent kinase 1 (CDK1) plays an essential role in cell cycle regulation.However,as mouse Cdk1embryos die early,the role of CDK1 in regulating the cell cycle and embryo development remains unclear.Here,we showed that zebrafish cdk1^(-/-)embryos exhibit severe microphthalmia accompanied by multiple defects in S phase entry,M phase progression,and cell differentiation but not in interkinetic nuclear migration.We identified Top2a as a potential downstream target and cyclin A2 and cyclin B1 as partners of Cdk1 in cell cycle regulation via an in silico analysis.While depletion of either cyclin A2 or Top2a led to the decreased S phase entry in zebrafish retinal cells,the depletion of cyclin B1 led to M phase arrest.Moreover,phosphorylation of Top2a at serine 1213 (S1213) was nearly abolished in both cdk1 and ccna2mutants,but not in ccnb1 mutants.Furthermore,overexpression of TOP2A^(S1213D),the phosphomimetic form of human TOP2A,rescued S phase entry and alleviated the microphthalmia defects in both cdk1^(-/-)and ccna2^(-/-)embryos.Taken together,our data suggest that Cdk1 interacts with cyclin A2 to regulate S phase entry partially through Top2a phosphorylation and interacts with cyclin B1 to regulate M phase progression.

关 键 词：CDK1 Cyclin A2 Cyclin B1 Top2a M phase S phase entry IKNM 

分 类 号：Q952[生物学—动物学]