title: A complex of Kif18b and MCAK promotes microtubule depolymerization and is negatively regulated by Aurora kinases.
abstract: BACKGROUND
  Spindle assembly requires tight control of microtubule (MT) dynamics. This is dependent on a variety of MT binding proteins and their upstream regulators. The Aurora kinases have several well-described functions during cell division, but it remains unclear whether they control global spindle microtubule dynamics.
  
  
  RESULTS
  Here, we find that simultaneous inhibition of Aurora A and B results in a dramatic decrease in spindle MT stability, and we identify the uncharacterized kinesin-8 Kif18b as a mediator of this effect. In interphase, Kif18b is nuclear, but upon nuclear envelope breakdown, Kif18b binds to astral MT plus ends through an interaction with EB1. Surprisingly, Kif18b also binds to the kinesin-13 motor MCAK, and this interaction is required for robust MT depolymerization. Furthermore, the Kif18b-MCAK interaction is negatively regulated by Aurora kinases through phosphorylation of MCAK, indicating that Aurora kinases regulate MT plus-end stability in mitosis through control of Kif18b-MCAK complex formation.
  
  
  CONCLUSIONS
  Together, these results uncover a novel role for Aurora kinases in regulating spindle MT dynamics through Kif18b-MCAK and suggest that the Kif18b-MCAK complex constitutes the major MT plus-end depolymerizing activity in mitotic cells.
authors.affiliation: Department of Experimental Oncology and Cancer Genomics Center, University Medical Center Utrecht, 3584 CG Utrecht, The Netherlands.
authors.forename: Marvin E
authors.initials: ME
authors.lastname: Tanenbaum
authors.forename: Libor
authors.initials: L
authors.lastname: Macurek
authors.forename: Babet
authors.initials: B
authors.lastname: van der Vaart
authors.forename: Matilde
authors.initials: M
authors.lastname: Galli
authors.forename: Anna
authors.initials: A
authors.lastname: Akhmanova
authors.forename: René H
authors.initials: RH
authors.lastname: Medema
mesh_terms: D064127:Aurora Kinases; D002460:Cell Line; D015853:Cysteine Proteinase Inhibitors / Q000378:metabolism; D006801:Humans; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D007976:Leupeptins / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism*; D008938:Mitosis / Q000502:physiology; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D015853:Cysteine Proteinase Inhibitors; C405804:EB1 microtubule binding proteins; C091489:KIF2C protein, human; D007976:Leupeptins; D008869:Microtubule-Associated Proteins; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; C552497:KIF18B protein, human; D016547:Kinesins; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde