PUBLICATION
Cyclin A2/cyclin-dependent kinase 1-dependent phosphorylation of Top2a is required for S phase entry during retinal development in zebrafish
- Authors
- Jin, M., Li, J., Hu, R., Xu, B., Huang, G., Huang, W., Chen, B., He, J., Cao, Y.
- ID
- ZDB-PUB-210410-2
- Date
- 2021
- Source
- Journal of genetics and genomics = Yi chuan xue bao 48(1): 63-74 (Journal)
- Registered Authors
- Cao, Ying, He, Jie
- Keywords
- Cdk1, Cyclin A2, Cyclin B1, IKNM, M phase, S phase entry, Top2a
- MeSH Terms
-
- Animals
- CDC2 Protein Kinase*/genetics
- CDC2 Protein Kinase*/metabolism
- Cyclin A2/metabolism
- Mice
- Phosphorylation
- S Phase/genetics
- Zebrafish*/genetics
- Zebrafish*/metabolism
- PubMed
- 33832859 Full text @ J. Genet. Genomics
Citation
Jin, M., Li, J., Hu, R., Xu, B., Huang, G., Huang, W., Chen, B., He, J., Cao, Y. (2021) Cyclin A2/cyclin-dependent kinase 1-dependent phosphorylation of Top2a is required for S phase entry during retinal development in zebrafish. Journal of genetics and genomics = Yi chuan xue bao. 48(1):63-74.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping