Centrosome cohesion is regulated by a balance of kinase and phosphatase activities
- PMID: 11707526
- DOI: 10.1242/jcs.114.20.3749
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.
Similar articles
-
NIMA-related kinase 2 (Nek2), a cell-cycle-regulated protein kinase localized to centrosomes, is complexed to protein phosphatase 1.Biochem J. 2000 Jul 15;349(Pt 2):509-18. doi: 10.1042/0264-6021:3490509. Biochem J. 2000. PMID: 10880350 Free PMC article.
-
Inhibitor-2 regulates protein phosphatase-1 complexed with NimA-related kinase to induce centrosome separation.J Biol Chem. 2002 Nov 15;277(46):44013-20. doi: 10.1074/jbc.M208035200. Epub 2002 Sep 6. J Biol Chem. 2002. PMID: 12221103
-
Protein phosphatase-1alpha regulates centrosome splitting through Nek2.Cancer Res. 2007 Feb 1;67(3):1082-9. doi: 10.1158/0008-5472.CAN-06-3071. Cancer Res. 2007. PMID: 17283141
-
The Nek2 protein kinase: a novel regulator of centrosome structure.Oncogene. 2002 Sep 9;21(40):6184-94. doi: 10.1038/sj.onc.1205711. Oncogene. 2002. PMID: 12214248 Review.
-
Cell cycle regulation by protein kinases and phosphatases.Ernst Schering Res Found Workshop. 2001;(34):19-46. doi: 10.1007/978-3-662-04645-6_2. Ernst Schering Res Found Workshop. 2001. PMID: 11394046 Review. No abstract available.
Cited by
-
Rootletin interacts with C-Nap1 and may function as a physical linker between the pair of centrioles/basal bodies in cells.Mol Biol Cell. 2006 Feb;17(2):1033-40. doi: 10.1091/mbc.e05-10-0943. Epub 2005 Dec 7. Mol Biol Cell. 2006. PMID: 16339073 Free PMC article.
-
CDK2-dependent phosphorylation of Suv39H1 is involved in control of heterochromatin replication during cell cycle progression.Nucleic Acids Res. 2014 Jun;42(10):6196-207. doi: 10.1093/nar/gku263. Epub 2014 Apr 11. Nucleic Acids Res. 2014. PMID: 24728993 Free PMC article.
-
A novel interaction between kinase activities in regulation of cilia formation.BMC Cell Biol. 2017 Nov 15;18(1):33. doi: 10.1186/s12860-017-0149-5. BMC Cell Biol. 2017. PMID: 29141582 Free PMC article.
-
Reversine, a 2,6-disubstituted purine, as an anti-cancer agent in differentiated and undifferentiated thyroid cancer cells.Pharm Res. 2012 Jul;29(7):1990-2005. doi: 10.1007/s11095-012-0727-3. Epub 2012 Apr 4. Pharm Res. 2012. PMID: 22477067
-
Characterization of Cep85 - a new antagonist of Nek2A that is involved in the regulation of centrosome disjunction.J Cell Sci. 2015 Sep 1;128(17):3290-303. doi: 10.1242/jcs.171637. Epub 2015 Jul 28. J Cell Sci. 2015. PMID: 26220856 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous
