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Mol Biol Cell July 1, 2008; 19 (7): 2752-65.
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Aurora A phosphorylates MCAK to control ran-dependent spindle bipolarity.

Zhang X , Ems-McClung SC , Walczak CE .

During mitosis, mitotic centromere-associated kinesin (MCAK) localizes to chromatin/kinetochores, a cytoplasmic pool, and spindle poles. Its localization and activity in the chromatin region are regulated by Aurora B kinase; however, how the cytoplasmic- and pole-localized MCAK are regulated is currently not clear. In this study, we used Xenopus egg extracts to form spindles in the absence of chromatin and centrosomes and found that MCAK localization and activity are tightly regulated by Aurora A. This regulation is important to focus microtubules at aster centers and to facilitate the transition from asters to bipolar spindles. In particular, we found that MCAK colocalized with NuMA and XMAP215 at the center of Ran asters where its activity is regulated by Aurora A-dependent phosphorylation of S196, which contributes to proper pole focusing. In addition, we found that MCAK localization at spindle poles was regulated through another Aurora A phosphorylation site (S719), which positively enhances bipolar spindle formation. This is the first study that clearly defines a role for MCAK at the spindle poles as well as identifies another key Aurora A substrate that contributes to spindle bipolarity.

PubMed ID: 18434591
PMC ID: PMC2441684
Article link: Mol Biol Cell
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: aurka aurkb ckap5 kif2c numa1 ran

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