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

SummaryOpposing 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.

Graphical AbstractFigure optionsDownload high-quality image (208 K)Download as PowerPoint slideHighlights
► PP1 binds CENP-E and binding is disrupted by Aurora phosphorylation
► Aurora kinases phosphorylate the kinetochore motor CENP-E at the spindle poles
► Phosphorylation of CENP-E is required for the congression of polar chromosomes
► Binding of PP1 to CENP-E is required for the stable attachment of these chromosomes