ICIS and Aurora B coregulate the microtubule depolymerase Kif2a

Curr Biol. 2009 May 12;19(9):758-63. doi: 10.1016/j.cub.2009.03.018. Epub 2009 Mar 26.


Kinesins in the mitotic spindle play major roles in determining spindle shape, size, and bipolarity, although specific regulation of these kinesins at distinct locations on the spindle is poorly understood. So that the forces that are required for spindle bipolarity are balanced, microtubule-depolymerizing kinesins are tightly regulated. Aurora B kinase phosphorylates the neck regions of the kinesin-13 family microtubule depolymerases Kif2a and mitotic centromere-associated kinesin (MCAK) and inhibits their depolymerase activities. How they are reactivated and how this is controlled independently on different kinetochore fibers is unknown. We show that inner centromere Kin-I stimulator (ICIS), which stimulates the related depolymerase MCAK, can reactivate Kif2a after Aurora B inhibition. When antibodies that block the ability of ICIS to activate Kif2a are injected into cells, monopolar spindles are generated. This phenotype is rescued by coinjection of anti-Nuf2 antibodies. We have performed a structure-function analysis of the ICIS protein and find that the N terminus of ICIS binds Aurora B and its regulators INCENP and TD60, whereas a central region binds MCAK, Kif2a, and microtubules, suggesting a scaffold function for ICIS. These data argue that ICIS and the chromosomal passenger complex (CPC) regulate Kif2a depolymerase activity.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Aurora Kinase B
  • Cell Line
  • Cloning, Molecular
  • DNA Primers / genetics
  • DNA, Complementary / genetics
  • Gene Expression Regulation / physiology*
  • Humans
  • Immunohistochemistry
  • Kinesin / genetics
  • Kinesin / metabolism*
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism*
  • Microtubules / metabolism*
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / metabolism*
  • Xenopus Proteins / genetics
  • Xenopus Proteins / metabolism*
  • Xenopus laevis


  • DNA Primers
  • DNA, Complementary
  • MTUS1 protein, Xenopus
  • Microtubule-Associated Proteins
  • Xenopus Proteins
  • Aurora Kinase B
  • Protein-Serine-Threonine Kinases
  • KIF2 protein, Xenopus
  • Kinesin