title: Centrosome cohesion is regulated by a balance of kinase and phosphatase activities.
abstract: Centrosome cohesion and separation are regulated throughout the cell cycle, but the underlying mechanisms are not well understood. Since overexpression of a protein kinase, Nek2, is able to trigger centrosome splitting (the separation of parental centrioles), we have surveyed a panel of centrosome-associated kinases for their ability to induce a similar phenotype. Cdk2, in association with either cyclin A or E, was as effective as Nek2, but several other kinases tested did not significantly interfere with centrosome cohesion. Centrosome splitting could also be triggered by inhibition of phosphatases, and protein phosphatase 1 alpha (PP1 alpha) was identified as a likely physiological antagonist of Nek2. Furthermore, we have revisited the role of the microtubule network in the control of centrosome cohesion. We could confirm that microtubule depolymerization by nocodazole causes centrosome splitting. Surprisingly, however, this drug-induced splitting also required kinase activity and could specifically be suppressed by a dominant-negative mutant of Nek2. These studies highlight the importance of protein phosphorylation in the control of centrosome cohesion, and they point to Nek2 and PP1 alpha as critical regulators of centrosome structure.
authors.affiliation: Department of Cell Biology, Max-Planck-Institute for Biochemistry, D-82152 Martinsried, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Meraldi
authors.forename: E A
authors.initials: EA
authors.lastname: Nigg
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D064127:Aurora Kinases; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins; D018385:Centrosome / Q000378:metabolism* / Q000648:ultrastructure; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D015638:Cytochalasin D / Q000494:pharmacology; D003599:Cytoskeleton / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008387:Marine Toxins; D008870:Microtubules / Q000378:metabolism; D000072379:NIMA-Related Kinases; D015739:Nocodazole / Q000494:pharmacology; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D019319:Okadaic Acid / Q000494:pharmacology; D010080:Oxazoles / Q000494:pharmacology; D017239:Paclitaxel / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010766:Phosphorylation; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D054645:Protein Phosphatase 1; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D014162:Transfection; D014407:Tumor Cells, Cultured; D029867:Xenopus Proteins; D000097869:Polo-Like Kinase 1
chemical_list: D000970:Antineoplastic Agents; D064127:Aurora Kinases; D018797:Cell Cycle Proteins; D018844:Cyclin-Dependent Kinases; D016213:Cyclins; D015638:Cytochalasin D; D004791:Enzyme Inhibitors; D008387:Marine Toxins; D000072379:NIMA-Related Kinases; D015739:Nocodazole; D019384:Nucleic Acid Synthesis Inhibitors; D019319:Okadaic Acid; D010080:Oxazoles; D017239:Paclitaxel; D010749:Phosphoprotein Phosphatases; D011494:Protein Kinases; D054645:Protein Phosphatase 1; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D029867:Xenopus Proteins; D000097869:Polo-Like Kinase 1; C059041:calyculin A; C112134:AURKA protein, Xenopus; C089441:NEK2 protein, human