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XB-ART-40193
Curr Biol May 12, 2009; 19 (9): 758-63.
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ICIS and Aurora B coregulate the microtubule depolymerase Kif2a.

Knowlton AL , Vorozhko VV , Lan W , Gorbsky GJ , Stukenberg PT .


Abstract
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.

PubMed ID: 19327998
PMC ID: PMC2775053
Article link: Curr Biol
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: aurkb incenp kif2a kif2c kin mtus1 nuf2
Antibodies: Aurkb Ab1

References [+] :
Andrews, Aurora B regulates MCAK at the mitotic centromere. 2004, Pubmed