title: Interplay between mitotic kinesins and the Aurora kinase-PP1 (protein phosphatase 1) axis.
abstract: Correct transmission of genetic information from mother to daughter cells is necessary for development and survival. Accurate segregation is achieved by bipolar attachment of sister kinetochores in each chromatid pair to spindle microtubules emanating from opposite spindle poles, a process known as chromosome bi-orientation. Achieving this requires dynamic interplay between kinetochore proteins, kinesin motor proteins and cell cycle regulators. Chromosome bi-orientation is monitored by a surveillance mechanism known as the SAC (spindle assembly checkpoint). The Aurora B kinase, which is bound to the inner centromere during early mitosis, plays a central role in both chromosome bi-orientation and the spindle checkpoint. The application of tension across centromeres establishes a spatial gradient of high phosphorylation activity at the inner centromere and low phosphorylation activity at the outer kinetochore. This gradient is further refined by the association of PP1 (protein phosphatase 1) to the outer kinetochore, which stabilizes kinetochore-microtubule interactions and silences the spindle checkpoint by dephosphorylating Aurora B kinase targets when chromosome bi-orientation is achieved. In the present review, I discuss emerging evidence that bidirectional cross-talk between mitotic kinesins and the Aurora kinase-PP1 axis is crucial for co-ordinating chromosome bi-orientation and spindle checkpoint signalling in eukaryotes.
authors.affiliation: *Division of Biomedical Cell Biology, Warwick Medical School, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, U.K.
authors.forename: John C
authors.initials: JC
authors.lastname: Meadows
mesh_terms: D064127:Aurora Kinases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D008938:Mitosis; D054645:Protein Phosphatase 1 / Q000235:genetics / Q000378:metabolism*; D015003:Yeasts / Q000166:cytology / Q000201:enzymology / Q000378:metabolism
chemical_list: D064127:Aurora Kinases; D054645:Protein Phosphatase 1; D016547:Kinesins