» Articles » PMID: 20660152

The Roles of Cyclin A2, B1, and B2 in Early and Late Mitotic Events

Overview
Journal Mol Biol Cell
Date 2010 Jul 28
PMID 20660152
Citations 87
Authors
Affiliations
Soon will be listed here.
Abstract

Here we have used siRNAs and time-lapse epifluorescence microscopy to examine the roles of various candidate mitotic cyclins in chromatin condensation in HeLa cells. Knocking down cyclin A2 resulted in a substantial (∼7 h) delay in chromatin condensation and histone H3 phosphorylation, and expressing an siRNA-resistant form of cyclin A2 partially rescued chromatin condensation. There was no detectable delay in DNA replication in the cyclin A2 knockdowns, arguing that the delay in chromatin condensation is not secondary to a delay in S-phase completion. Cyclin A2 is required for the activation and nuclear accumulation of cyclin B1-Cdk1, raising the possibility that cyclin B1-Cdk1 mediates the effects of cyclin A2. Consistent with this possibility, we found that chromatin condensation was tightly associated temporally with the redistribution of cyclin B1 to the nucleus. Moreover, a constitutively nuclear cyclin B1 rescued chromatin condensation in cyclin A2 knockdown cells. On the other hand, knocking down cyclin B1 delayed chromatin condensation by only about one hour. Our working hypothesis is that active, nuclear cyclin B1-Cdk1 normally cooperates with cyclin A2 to bring about early mitotic events. Because cyclin A2 is present only during the early stages of mitosis, we asked whether cyclin B knockdown might have more dramatic defects on late mitotic events. Consistent with this possibility, we found that cyclin B1- and cyclin B1/B2-knockdown cells had difficulty in maintaining a mitotic arrest in the presence of nocodazole. Taken together, these data suggest that cyclin A2 helps initiate mitosis, in part through its effects on cyclin B1, and that cyclins B1 and B2 are particularly critical for the maintenance of the mitotic state.

Citing Articles

Low Temperature Plasma Jet Treatment Promotes Skin Wound Healing by Enhancing Cell Proliferation via the PI3K-AKT and AMPK Pathways.

Zhu Y, Lian X, Li K, Zhang J, Wu W, Zhang X Int Wound J. 2025; 22(2):e70213.

PMID: 39934939 PMC: 11813701. DOI: 10.1111/iwj.70213.


Role of spindle assembly checkpoint proteins in gametogenesis and embryogenesis.

Pun R, North B Front Cell Dev Biol. 2025; 12:1491394.

PMID: 39911185 PMC: 11794522. DOI: 10.3389/fcell.2024.1491394.


Positively charged specificity site in cyclin B1 is essential for mitotic fidelity.

Heinzle C, Hofler A, Yu J, Heid P, Kremer N, Schunk R Nat Commun. 2025; 16(1):853.

PMID: 39833154 PMC: 11747444. DOI: 10.1038/s41467-024-55669-x.


Cyclin A/Cdk1 promotes chromosome alignment and timely mitotic progression.

Valles S, Bural S, Godek K, Compton D Mol Biol Cell. 2024; 35(11):ar141.

PMID: 39356777 PMC: 11617097. DOI: 10.1091/mbc.E23-12-0479.


Y-box binding protein 1/cyclin A1 axis specifically promotes cell cycle progression at G/M phase in ovarian cancer.

Murakami Y, Katsuchi D, Matsumoto T, Kanazawa K, Shibata T, Kawahara A Sci Rep. 2024; 14(1):21701.

PMID: 39289424 PMC: 11408696. DOI: 10.1038/s41598-024-72174-9.


References
1.
Lohka M, Hayes M, Maller J . Purification of maturation-promoting factor, an intracellular regulator of early mitotic events. Proc Natl Acad Sci U S A. 1988; 85(9):3009-13. PMC: 280132. DOI: 10.1073/pnas.85.9.3009. View

2.
Takenaka K, Moriguchi T, Nishida E . Activation of the protein kinase p38 in the spindle assembly checkpoint and mitotic arrest. Science. 1998; 280(5363):599-602. DOI: 10.1126/science.280.5363.599. View

3.
den Elzen N, Pines J . Cyclin A is destroyed in prometaphase and can delay chromosome alignment and anaphase. J Cell Biol. 2001; 153(1):121-36. PMC: 2185531. DOI: 10.1083/jcb.153.1.121. View

4.
Novak B, Tyson J . Numerical analysis of a comprehensive model of M-phase control in Xenopus oocyte extracts and intact embryos. J Cell Sci. 1993; 106 ( Pt 4):1153-68. DOI: 10.1242/jcs.106.4.1153. View

5.
Gu Y, Turck C, MORGAN D . Inhibition of CDK2 activity in vivo by an associated 20K regulatory subunit. Nature. 1993; 366(6456):707-10. DOI: 10.1038/366707a0. View