Cyclin A/cdk2 coordinates centrosomal and nuclear mitotic events.
Cyclin A/cdk2 has a role in progression through S phase, and a large pool is also activated in G2 phase. Here we report that this G2 phase pool regulates the timing of progression into mitosis. Knock down of cyclin A by siRNA or addition of a specific cdk2 small molecule inhibitor delayed entry into mitosis by delaying cells in G2 phase. The G2 phase-delayed cells contained elevated levels of inactive cyclin B/cdk1. However, increased microtubule nucleation at the centrosomes was observed, and the centrosomes stained for markers of cyclin B/cdk1 activity. Both microtubule nucleation at the centrosomes and the phosphoprotein markers were lost with short-term treatment of the cdk1/2 inhibitor roscovitine but not the Mek1/2 inhibitor U0126. Cyclin A/cdk2 localized at the centrosomes in late G2 phase after separation of the centrosomes but before the start of prophase. Thus G2 phase cyclin A/cdk2 controls the timing of entry into mitosis by controlling the subsequent activation of cyclin B/cdk1, but also has an unexpected role in coordinating the activation of cyclin B/cdk1 at the centrosome and in the nucleus.
De Boer
L
L
Cancer Biology Program, Diamantina Institute for Cancer, Immunology and Metabolic Medicine, University of Queensland, Princess Alexandra Hospital, Brisbane, Queensland, Australia.
Oakes
V
V
Beamish
H
H
Giles
N
N
Stevens
F
F
Somodevilla-Torres
M
M
Desouza
C
C
Gabrielli
B
B
D002070:Butadienes / Q000494:pharmacology; D002460:Cell Line; D002467:Cell Nucleus / Q000502:physiology*; D018385:Centrosome / Q000502:physiology*; D019925:Cyclin A / Q000502:physiology*; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016193:G1 Phase; D006367:HeLa Cells; D006801:Humans; D048369:MAP Kinase Kinase 1 / Q000378:metabolism; D048370:MAP Kinase Kinase 2 / Q000378:metabolism; D008938:Mitosis; D009570:Nitriles / Q000494:pharmacology; D011687:Purines / Q000494:pharmacology; D034741:RNA, Small Interfering; D000077546:Roscovitine
D002070:Butadienes; D019925:Cyclin A; D004791:Enzyme Inhibitors; D009570:Nitriles; D011687:Purines; D034741:RNA, Small Interfering; C113580:U 0126; D000077546:Roscovitine; C482128:MAP2K2 protein, human; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2