title: INCENP binds the Aurora-related kinase AIRK2 and is required to target it to chromosomes, the central spindle and cleavage furrow.
abstract: Cytoskeletal rearrangements during mitosis must be co-ordinated with chromosome movements. The 'chromosomal passenger' proteins [1], which include the inner centromere protein (INCENP [2]), the Aurora-related serine-threonine protein kinase AIRK2 [3,4] and the unidentified human autoantigen TD-60 [5], have been suggested to integrate mitotic events. These proteins are chromosomal until metaphase but subsequently transfer to the midzone microtubule array and the equatorial cortex during anaphase. Disruption of INCENP function affects both chromosome segregation and completion of cytokinesis [6,7], whereas interference with AIRK2 function primarily affects cytokinesis [3,8]. Here, we report that INCENP is stockpiled in Xenopus eggs in a complex with Xenopus AIRK2 (XAIRK2), and that INCENP and AIRK2 kinase bind one another in vitro. This association was found to be evolutionarily conserved. Sli15p, the binding partner of yeast Aurora kinase Ipl1p, can be recognized as an INCENP family member because of the presence of a conserved carboxy-terminal sequence region, which we term the IN box. This interaction between INCENP and Aurora kinase was found to be biologically relevant. INCENP and AIRK2 colocalized exactly in human cells, and INCENP was required to target AIRK2 correctly to centromeres and the central spindle.
authors.affiliation: Wellcome Institute for Cell Biology, Edinburgh, UK.
authors.forename: R R
authors.initials: RR
authors.lastname: Adams
authors.forename: S P
authors.initials: SP
authors.lastname: Wheatley
authors.forename: A M
authors.initials: AM
authors.lastname: Gouldsworthy
authors.forename: S E
authors.initials: SE
authors.lastname: Kandels-Lewis
authors.forename: M
authors.initials: M
authors.lastname: Carmena
authors.forename: C
authors.initials: C
authors.lastname: Smythe
authors.forename: D L
authors.initials: DL
authors.lastname: Gerloff
authors.forename: W C
authors.initials: WC
authors.lastname: Earnshaw
mesh_terms: D000595:Amino Acid Sequence; D064127:Aurora Kinases; D002503:Centromere / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry / Q000378:metabolism*; D002877:Chromosomes, Human; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D003598:Cytoskeletal Proteins; C083767:INCENP protein, human; C513185:Incenp protein, mouse; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases