title: Cyclin-dependent kinase 2 (Cdk2) is required for centrosome duplication in mammalian cells.
abstract: Centrosome duplication is indispensable for the formation of the bipolar mitotic spindle. Surprisingly, even if DNA replication or mitosis is inhibited, centrosome duplication can still occur [1] [2] [3] [4] [5]. Thus, it remains unknown how centrosome duplication is coordinated with the cell cycle. Here, we show that centrosome duplication requires cyclin-dependent kinase 2 (Cdk2) in mammalian cells. We have found that in Chinese hamster ovary (CHO) cells, whereas centrosome duplication is not inhibited by hydroxyurea (HU) treatment, which arrests the cells in S phase, it is inhibited by mimosine treatment, which arrests the cells in late G1 phase. Cdk2 activity was higher in HU-treated cells than in mimosine-treated cells. Remarkably, inhibition of the Cdk2 activity in HU-treated cells with butyrolactone I or roscovitine [6], or by expression of the Cdk inhibitor p21(Waf1/Cip1), blocked the continued centrosome duplication. Moreover, overexpression of Cdk2 reversed the inhibition of centrosome duplication by mimosine treatment. These results indicate a requirement of Cdk2 activity for centrosome duplication and therefore suggest an underlying mechanism for the coordination of centrosome duplication with the cell cycle.
authors.affiliation: Department of Biophysics, Graduate School of Science, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: K
authors.initials: K
authors.lastname: Hayashi
authors.forename: E
authors.initials: E
authors.lastname: Nishida
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D042846:CDC2-CDC28 Kinases; D016466:CHO Cells / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D002453:Cell Cycle / Q000187:drug effects; D018385:Centrosome / Q000187:drug effects / Q000378:metabolism*; D006224:Cricetinae; D051357:Cyclin-Dependent Kinase 2; D050759:Cyclin-Dependent Kinase Inhibitor p21; D018844:Cyclin-Dependent Kinases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D016213:Cyclins / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016193:G1 Phase / Q000187:drug effects; D015870:Gene Expression; D006918:Hydroxyurea / Q000494:pharmacology; D008898:Mimosine / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D011687:Purines / Q000494:pharmacology; D000077546:Roscovitine; D016196:S Phase / Q000187:drug effects
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D011687:Purines; D000077546:Roscovitine; D008898:Mimosine; C082868:butyrolactone I; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases; D015107:4-Butyrolactone; D006918:Hydroxyurea