title: The chromosomal passenger complex activates Polo kinase at centromeres.
abstract: The coordinated activities at centromeres of two key cell cycle kinases, Polo and Aurora B, are critical for ensuring that the two sister kinetochores of each chromosome are attached to microtubules from opposite spindle poles prior to chromosome segregation at anaphase. Initial attachments of chromosomes to the spindle involve random interactions between kinetochores and dynamic microtubules, and errors occur frequently during early stages of the process. The balance between microtubule binding and error correction (e.g., release of bound microtubules) requires the activities of Polo and Aurora B kinases, with Polo promoting stable attachments and Aurora B promoting detachment. Our study concerns the coordination of the activities of these two kinases in vivo. We show that INCENP, a key scaffolding subunit of the chromosomal passenger complex (CPC), which consists of Aurora B kinase, INCENP, Survivin, and Borealin/Dasra B, also interacts with Polo kinase in Drosophila cells. It was known that Aurora A/Bora activates Polo at centrosomes during late G2. However, the kinase that activates Polo on chromosomes for its critical functions at kinetochores was not known. We show here that Aurora B kinase phosphorylates Polo on its activation loop at the centromere in early mitosis. This phosphorylation requires both INCENP and Aurora B activity (but not Aurora A activity) and is critical for Polo function at kinetochores. Our results demonstrate clearly that Polo kinase is regulated differently at centrosomes and centromeres and suggest that INCENP acts as a platform for kinase crosstalk at the centromere. This crosstalk may enable Polo and Aurora B to achieve a balance wherein microtubule mis-attachments are corrected, but proper attachments are stabilized allowing proper chromosome segregation.
authors.affiliation: Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, Scotland, United Kingdom. mar.carmena@ed.ac.uk
authors.forename: Mar
authors.initials: M
authors.lastname: Carmena
authors.forename: Xavier
authors.initials: X
authors.lastname: Pinson
authors.forename: Melpi
authors.initials: M
authors.lastname: Platani
authors.forename: Zeina
authors.initials: Z
authors.lastname: Salloum
authors.forename: Zhenjie
authors.initials: Z
authors.lastname: Xu
authors.forename: Anthony
authors.initials: A
authors.lastname: Clark
authors.forename: Fiona
authors.initials: F
authors.lastname: Macisaac
authors.forename: Hiromi
authors.initials: H
authors.lastname: Ogawa
authors.forename: Ulrike
authors.initials: U
authors.lastname: Eggert
authors.forename: David M
authors.initials: DM
authors.lastname: Glover
authors.forename: Vincent
authors.initials: V
authors.lastname: Archambault
authors.forename: William C
authors.initials: WC
authors.lastname: Earnshaw
mesh_terms: D000818:Animals; D064107:Aurora Kinase B; D064127:Aurora Kinases; D018929:Cell Culture Techniques; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D020090:Chromosome Segregation / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000201:enzymology / Q000235:genetics; D004789:Enzyme Activation; D015971:Gene Expression Regulation, Enzymologic; D006367:HeLa Cells; D006801:Humans; D018386:Kinetochores / Q000201:enzymology*; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis / Q000235:genetics; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D008941:Spindle Apparatus / Q000235:genetics / Q000378:metabolism
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D029721:Drosophila Proteins; C512039:Incenp protein, Drosophila; C072004:polo protein, Drosophila; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases