Jingyu Li
Ruikun Hu
Baijie Xu
Guanliang Huang
Weilai Huang
Bo Chen
Jie He
Ying Cao
aDepartment of Clinical Laboratory Medicine of Shanghai Tenth People’s Hospital, Tongji University School of Life Sciences and Technology, Shanghai 200092, China
bInstitute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China
cUniversity of Chinese Academy of Sciences, Beijing 100049, China
More InformationCorresponding author: E-mail address: yingcao@tongji.edu.cn (Ying Cao)
Publish Date:2021-01-20
Abstract
Abstract
Cyclin-dependent kinase 1 (CDK1) plays an essential role in cell cycle regulation. However, as mouse Cdk1 embryos 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 ccna2 mutants, but not in ccnb1 mutants. Furthermore, overexpression of TOP2AS1213D, 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.Keywords: Cdk1,
Cyclin A2,
Cyclin B1,
Top2a,
M phase,
S phase entry,
IKNM
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http://www.jgenetgenomics.org/article/exportPdf?id=23302004-363f-45a8-89bf-f56097ab995c&language=en
