Cyclin A/cdk2 coordinates centrosomal and nuclear mitotic events
doi: 10.1038/onc.2008.74
pmid: 18372919
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.
- Queensland University of Technology Australia
- The Ohio State University United States
- University of Queensland Australia
- Princess Alexandra Hospital Australia
- University of Queensland Australia
571, MAP Kinase Kinase 2, MAP Kinase Kinase 1, Mitosis, Proliferation and Death, Cyclin A, Cell Line, cyclin A/cdk2, C1, Nitriles, Butadienes, Roscovitine, 920102 Cancer and Related Disorders, Humans, Enzyme Inhibitors, RNA, Small Interfering, Cyclin A/cdk2, Cell Nucleus, Centrosome, G2/M, Cyclin-Dependent Kinase 2, G1 Phase, 1103 Clinical Sciences, 060103 Cell Development, centrosome, Purines, HeLa Cells
571, MAP Kinase Kinase 2, MAP Kinase Kinase 1, Mitosis, Proliferation and Death, Cyclin A, Cell Line, cyclin A/cdk2, C1, Nitriles, Butadienes, Roscovitine, 920102 Cancer and Related Disorders, Humans, Enzyme Inhibitors, RNA, Small Interfering, Cyclin A/cdk2, Cell Nucleus, Centrosome, G2/M, Cyclin-Dependent Kinase 2, G1 Phase, 1103 Clinical Sciences, 060103 Cell Development, centrosome, Purines, HeLa Cells
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