Aurora Kinases and Protein Phosphatase 1 Mediate Chromosome Congression Through Regulation of CENP-E

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2010 Aug 10

PMID 20691903

Citations 149

Authors

Yumi Kim

Andrew J Holland

Weijie Lan

Don W Cleveland

Affiliations

Soon will be listed here.

Abstract

Opposing roles of Aurora kinases and protein phosphatase 1 (PP1) during mitosis have long been suggested. Here, we demonstrate that Aurora kinases A and B phosphorylate a conserved residue on the kinetochore motor CENP-E. PP1 binds CENP-E via a motif overlapping this phosphorylation site and binding is disrupted by Aurora phosphorylation. Phosphorylation of CENP-E by the Auroras is enriched at spindle poles, disrupting binding of PP1 and reducing CENP-E's affinity for individual microtubules. This phosphorylation is required for CENP-E-mediated towing of initially polar chromosomes toward the cell center. Kinetochores on such chromosomes cannot make subsequent stable attachment to spindle microtubules when dephosphorylation of CENP-E or rebinding of PP1 to CENP-E is blocked. Thus, an Aurora/PP1 phosphorylation switch modulates CENP-E motor activity as an essential feature of chromosome congression from poles and localized PP1 delivery by CENP-E to the outer kinetochore is necessary for stable microtubule capture by those chromosomes.

Citing Articles

Fibrous corona is reduced in cancer cell lines that attenuate microtubule nucleation from kinetochores.

Ishikawa Y, Fukue H, Iwakami R, Ikeda M, Iemura K, Tanaka K Cancer Sci. 2024; 116(2):420-431.

PMID: 39604214 PMC: 11786318. DOI: 10.1111/cas.16406.

Mutation of the SUMOylation site of Aurora-B disrupts spindle formation and chromosome alignment in oocytes.

Chen S, Li L, Yao B, Guo J, Lu P, Zhang H Cell Death Discov. 2024; 10(1):447.

PMID: 39438456 PMC: 11496499. DOI: 10.1038/s41420-024-02217-7.

A kinetochore-associated kinesin-7 motor cooperates with BUB3.3 to regulate mitotic chromosome congression in Arabidopsis thaliana.

Tang X, He Y, Tang Y, Chen K, Lin H, Liu B Nat Plants. 2024; 10(11):1724-1736.

PMID: 39414927 DOI: 10.1038/s41477-024-01824-7.

Contribution of AurkA/TPX2 Overexpression to Chromosomal Imbalances and Cancer.

Polverino F, Mastrangelo A, Guarguaglini G Cells. 2024; 13(16).

PMID: 39195284 PMC: 11353082. DOI: 10.3390/cells13161397.

Cross-Reactivity of N6AMT1 Antibodies with Aurora Kinase A: An Example of Antibody-Specific Non-Specificity.

Brumele B, Serova E, Lupp A, Suija M, Mutso M, Kurg R Antibodies (Basel). 2024; 13(2).

PMID: 38804301 PMC: 11130794. DOI: 10.3390/antib13020033.

References

Trinkle-Mulcahy L, Andersen J, Lam Y, Moorhead G, Mann M, Lamond A . Repo-Man recruits PP1 gamma to chromatin and is essential for cell viability. J Cell Biol. 2006; 172(5):679-92. PMC: 2063701. DOI: 10.1083/jcb.200508154. View

Cimini D, Wan X, Hirel C, Salmon E . Aurora kinase promotes turnover of kinetochore microtubules to reduce chromosome segregation errors. Curr Biol. 2006; 16(17):1711-8. DOI: 10.1016/j.cub.2006.07.022. View

Espeut J, Gaussen A, Bieling P, Morin V, Prieto S, Fesquet D . Phosphorylation relieves autoinhibition of the kinetochore motor Cenp-E. Mol Cell. 2008; 29(5):637-43. DOI: 10.1016/j.molcel.2008.01.004. View

Harrington E, Bebbington D, Moore J, Rasmussen R, Ajose-Adeogun A, Nakayama T . VX-680, a potent and selective small-molecule inhibitor of the Aurora kinases, suppresses tumor growth in vivo. Nat Med. 2004; 10(3):262-7. DOI: 10.1038/nm1003. View

Helenius J, Brouhard G, Kalaidzidis Y, Diez S, Howard J . The depolymerizing kinesin MCAK uses lattice diffusion to rapidly target microtubule ends. Nature. 2006; 441(7089):115-9. DOI: 10.1038/nature04736. View

Kim Y, Heuser J, Waterman C, Cleveland D . CENP-E combines a slow, processive motor and a flexible coiled coil to produce an essential motile kinetochore tether. J Cell Biol. 2008; 181(3):411-9. PMC: 2364708. DOI: 10.1083/jcb.200802189. View

CASE R, Pierce D, Hart C, Vale R . The directional preference of kinesin motors is specified by an element outside of the motor catalytic domain. Cell. 1997; 90(5):959-66. DOI: 10.1016/s0092-8674(00)80360-8. View

Marumoto T, Zhang D, Saya H . Aurora-A - a guardian of poles. Nat Rev Cancer. 2005; 5(1):42-50. DOI: 10.1038/nrc1526. View

Putkey F, Cramer T, Morphew M, Silk A, Johnson R, McIntosh J . Unstable kinetochore-microtubule capture and chromosomal instability following deletion of CENP-E. Dev Cell. 2002; 3(3):351-65. DOI: 10.1016/s1534-5807(02)00255-1. View

10.

Shaner N, Lin M, McKeown M, Steinbach P, Hazelwood K, Davidson M . Improving the photostability of bright monomeric orange and red fluorescent proteins. Nat Methods. 2008; 5(6):545-51. PMC: 2853173. DOI: 10.1038/nmeth.1209. View

11.

Cleveland D, Mao Y, Sullivan K . Centromeres and kinetochores: from epigenetics to mitotic checkpoint signaling. Cell. 2003; 112(4):407-21. DOI: 10.1016/s0092-8674(03)00115-6. View

12.

Berger B, Wilson D, Wolf E, Tonchev T, Milla M, Kim P . Predicting coiled coils by use of pairwise residue correlations. Proc Natl Acad Sci U S A. 1995; 92(18):8259-63. PMC: 41136. DOI: 10.1073/pnas.92.18.8259. View

13.

Tanaka T, Rachidi N, Janke C, Pereira G, Galova M, Schiebel E . Evidence that the Ipl1-Sli15 (Aurora kinase-INCENP) complex promotes chromosome bi-orientation by altering kinetochore-spindle pole connections. Cell. 2002; 108(3):317-29. DOI: 10.1016/s0092-8674(02)00633-5. View

14.

Okada Y, Hirokawa N . A processive single-headed motor: kinesin superfamily protein KIF1A. Science. 1999; 283(5405):1152-7. DOI: 10.1126/science.283.5405.1152. View

15.

Emanuele M, Lan W, Jwa M, Miller S, Chan C, Stukenberg P . Aurora B kinase and protein phosphatase 1 have opposing roles in modulating kinetochore assembly. J Cell Biol. 2008; 181(2):241-54. PMC: 2315672. DOI: 10.1083/jcb.200710019. View

16.

Weaver B, Bonday Z, Putkey F, Kops G, Silk A, Cleveland D . Centromere-associated protein-E is essential for the mammalian mitotic checkpoint to prevent aneuploidy due to single chromosome loss. J Cell Biol. 2003; 162(4):551-63. PMC: 2173788. DOI: 10.1083/jcb.200303167. View

17.

Sassoon I, Severin F, Andrews P, Taba M, Kaplan K, Ashford A . Regulation of Saccharomyces cerevisiae kinetochores by the type 1 phosphatase Glc7p. Genes Dev. 1999; 13(5):545-55. PMC: 316511. DOI: 10.1101/gad.13.5.545. View

18.

Liao H, Li G, Yen T . Mitotic regulation of microtubule cross-linking activity of CENP-E kinetochore protein. Science. 1994; 265(5170):394-8. DOI: 10.1126/science.8023161. View

19.

Hendrickx A, Beullens M, Ceulemans H, Abt T, Van Eynde A, Nicolaescu E . Docking motif-guided mapping of the interactome of protein phosphatase-1. Chem Biol. 2009; 16(4):365-71. DOI: 10.1016/j.chembiol.2009.02.012. View

20.

Kapoor T, Lampson M, Hergert P, Cameron L, Cimini D, Salmon E . Chromosomes can congress to the metaphase plate before biorientation. Science. 2006; 311(5759):388-91. PMC: 4768465. DOI: 10.1126/science.1122142. View