Aurora kinases and protein phosphatase 1 mediate chromosome congression through regulation of CENP-E.
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.
Kim
Yumi
Y
Ludwig Institute for Cancer Research, University of California, San Diego, La Jolla, CA 92093, USA.
Holland
Andrew J
AJ
Lan
Weijie
W
Cleveland
Don W
DW
D000595:Amino Acid Sequence; D000818:Animals; D064127:Aurora Kinases; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D002875:Chromosomes / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D018386:Kinetochores / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D008969:Molecular Sequence Data; D010766:Phosphorylation; D054645:Protein Phosphatase 1 / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D008941:Spindle Apparatus / Q000378:metabolism; D014982:Xenopus laevis / Q000378:metabolism*
D002868:Chromosomal Proteins, Non-Histone; C068688:centromere protein E; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D054645:Protein Phosphatase 1