Cyclin A/cdk2 coordinates centrosomal and nuclear mitotic events

De Boer, L., Oakes, V., Beamish, H., Giles, N., Stevens, F., Somodevilla Torres, M., DeSouza, C. and Gabrielli, B. (2008) Cyclin A/cdk2 coordinates centrosomal and nuclear mitotic events. Oncogene, 27 31: 4261-4268. doi:10.1038/onc.2008.74


Author De Boer, L.
Oakes, V.
Beamish, H.
Giles, N.
Stevens, F.
Somodevilla Torres, M.
DeSouza, C.
Gabrielli, B.
Title Cyclin A/cdk2 coordinates centrosomal and nuclear mitotic events
Journal name Oncogene   Check publisher's open access policy
ISSN 0950-9232
1476-5594
Publication date 2008-07-17
Year available 2008
Sub-type Article (original research)
DOI 10.1038/onc.2008.74
Open Access Status
Volume 27
Issue 31
Start page 4261
End page 4268
Total pages 8
Place of publication London, U. K.
Publisher Nature Publishing Group
Language eng
Subject C1
060103 Cell Development, Proliferation and Death
920102 Cancer and Related Disorders
1103 Clinical Sciences
Abstract Cyclin A/cdk2 has a role in progression through Sphase, and a large pool is also activated in G(2) phase. Here we report that this G(2) 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 G(2) phase. The G(2) 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 G(2) phase after separation of the centrosomes but before the start of prophase. Thus G(2) 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.
Formatted abstract
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.
© 2008 Macmillan Publishers Limited All rights reserved
Keyword Cyclin A/cdk2
G2/M
Centrosome
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

 
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Created: Tue, 24 Mar 2009, 23:03:04 EST by Kylie Hengst on behalf of UQ Diamantina Institute