Cdk1 Regulates Centrosome Separation by Restraining Proteolysis of Microtubule-associated Proteins

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2006 May 12

PMID 16688214

Citations 45

Authors

Karen Crasta

Phillips Huang

Garry Morgan

Mark Winey

Uttam Surana

Affiliations

Soon will be listed here.

Abstract

In yeast, separation of duplicated spindle pole bodies (SPBs) (centrosomes in higher eukaryotes) is an indispensable step in the assembly of mitotic spindle and is triggered by severing of the bridge that connects the sister SPBs. This process requires Cdk1 (Cdc28) activation by Tyrosine 19 dephosphorylation. We show that cells that fail to activate Cdk1 are devoid of spindles due to persistently active APCCdh1, which targets microtubule-associated proteins Cin8, Kip1 and Ase1 for degradation. Tyrosine 19 dephosphorylation of Cdk1 is necessary to specifically prevent proteolysis of these proteins. Interestingly, SPB separation is dependent on the microtubule-bundling activity of Cin8 but not on its motor function. Since ectopic expression of proteolysis-resistant Cin8, Kip1 or Ase1 is sufficient for SPB separation even in the absence of Cdc28-Clb activity, we suggest that stabilization of these mechanical force-generating proteins is the predominant role of Cdc28-Clb in centrosome separation.

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References

Lane H, Nigg E . Antibody microinjection reveals an essential role for human polo-like kinase 1 (Plk1) in the functional maturation of mitotic centrosomes. J Cell Biol. 1996; 135(6 Pt 2):1701-13. PMC: 2133970. DOI: 10.1083/jcb.135.6.1701. View

Schuyler S, Liu J, Pellman D . The molecular function of Ase1p: evidence for a MAP-dependent midzone-specific spindle matrix. Microtubule-associated proteins. J Cell Biol. 2003; 160(4):517-28. PMC: 2173742. DOI: 10.1083/jcb.200210021. View

OToole E, Winey M, McIntosh J . High-voltage electron tomography of spindle pole bodies and early mitotic spindles in the yeast Saccharomyces cerevisiae. Mol Biol Cell. 1999; 10(6):2017-31. PMC: 25406. DOI: 10.1091/mbc.10.6.2017. View

Ubersax J, Woodbury E, Quang P, Paraz M, Blethrow J, Shah K . Targets of the cyclin-dependent kinase Cdk1. Nature. 2003; 425(6960):859-64. DOI: 10.1038/nature02062. View

Castro A, Bernis C, Vigneron S, Labbe J, Lorca T . The anaphase-promoting complex: a key factor in the regulation of cell cycle. Oncogene. 2005; 24(3):314-25. DOI: 10.1038/sj.onc.1207973. View

Glover D, Leibowitz M, McLean D, Parry H . Mutations in aurora prevent centrosome separation leading to the formation of monopolar spindles. Cell. 1995; 81(1):95-105. DOI: 10.1016/0092-8674(95)90374-7. View

Yeong F, Lim H, Wang Y, Surana U . Early expressed Clb proteins allow accumulation of mitotic cyclin by inactivating proteolytic machinery during S phase. Mol Cell Biol. 2001; 21(15):5071-81. PMC: 87233. DOI: 10.1128/MCB.21.15.5071-5081.2001. View

Blangy A, Lane H, dHerin P, Harper M, Kress M, Nigg E . Phosphorylation by p34cdc2 regulates spindle association of human Eg5, a kinesin-related motor essential for bipolar spindle formation in vivo. Cell. 1995; 83(7):1159-69. DOI: 10.1016/0092-8674(95)90142-6. View

Bishop A, Ubersax J, Petsch D, Matheos D, Gray N, Blethrow J . A chemical switch for inhibitor-sensitive alleles of any protein kinase. Nature. 2000; 407(6802):395-401. DOI: 10.1038/35030148. View

10.

Fitch I, Dahmann C, Surana U, Amon A, Nasmyth K, Goetsch L . Characterization of four B-type cyclin genes of the budding yeast Saccharomyces cerevisiae. Mol Biol Cell. 1992; 3(7):805-18. PMC: 275636. DOI: 10.1091/mbc.3.7.805. View

11.

Juang Y, Huang J, Peters J, McLaughlin M, Tai C, Pellman D . APC-mediated proteolysis of Ase1 and the morphogenesis of the mitotic spindle. Science. 1997; 275(5304):1311-4. DOI: 10.1126/science.275.5304.1311. View

12.

Winey M, Mamay C, OToole E, Mastronarde D, Giddings Jr T, McDonald K . Three-dimensional ultrastructural analysis of the Saccharomyces cerevisiae mitotic spindle. J Cell Biol. 1995; 129(6):1601-15. PMC: 2291174. DOI: 10.1083/jcb.129.6.1601. View

13.

Sawin K, Mitchison T . Mutations in the kinesin-like protein Eg5 disrupting localization to the mitotic spindle. Proc Natl Acad Sci U S A. 1995; 92(10):4289-93. PMC: 41929. DOI: 10.1073/pnas.92.10.4289. View

14.

Bullitt E, Rout M, Kilmartin J, Akey C . The yeast spindle pole body is assembled around a central crystal of Spc42p. Cell. 1997; 89(7):1077-86. DOI: 10.1016/s0092-8674(00)80295-0. View

15.

Gordon D, Roof D . Degradation of the kinesin Kip1p at anaphase onset is mediated by the anaphase-promoting complex and Cdc20p. Proc Natl Acad Sci U S A. 2001; 98(22):12515-20. PMC: 60085. DOI: 10.1073/pnas.231212498. View

16.

Hoyt M, He L, Loo K, Saunders W . Two Saccharomyces cerevisiae kinesin-related gene products required for mitotic spindle assembly. J Cell Biol. 1992; 118(1):109-20. PMC: 2289527. DOI: 10.1083/jcb.118.1.109. View

17.

Byers B, Goetsch L . Behavior of spindles and spindle plaques in the cell cycle and conjugation of Saccharomyces cerevisiae. J Bacteriol. 1975; 124(1):511-23. PMC: 235921. DOI: 10.1128/jb.124.1.511-523.1975. View

18.

Lim H, Goh P, Surana U . Spindle pole body separation in Saccharomyces cerevisiae requires dephosphorylation of the tyrosine 19 residue of Cdc28. Mol Cell Biol. 1996; 16(11):6385-97. PMC: 231640. DOI: 10.1128/MCB.16.11.6385. View

19.

Giet R, Uzbekov R, Cubizolles F, Le Guellec K, Prigent C . The Xenopus laevis aurora-related protein kinase pEg2 associates with and phosphorylates the kinesin-related protein XlEg5. J Biol Chem. 1999; 274(21):15005-13. DOI: 10.1074/jbc.274.21.15005. View

20.

Surana U, Robitsch H, Price C, Schuster T, Fitch I, Futcher A . The role of CDC28 and cyclins during mitosis in the budding yeast S. cerevisiae. Cell. 1991; 65(1):145-61. DOI: 10.1016/0092-8674(91)90416-v. View