A Journal of Postdoctoral Research.
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Role of the Spindle and kinetochore associated (Ska) protein complex in mitotic progressi
Sushama Sivakumar, Ph.D.
1University of Texas Southwestern Medical Center
UTSMC, Dallas, TX, 75390 USA.

The Spindle and Kinetochore Associated (Ska) protein complex is a heterotrimeric complex involved in mitotic progression. Depletion of Ska1, Ska2 or Ska3 by RNAi causes delays in chromosome alignment followed by a long metaphase arrest that results in Cohesion fatigue. Ska1 and Ska3 have been shown to bind microtubules both in vitro and in vivo. Ska1 directly recruits the protein phosphatase PP1 to kinetochores during mitosis. The Ska complex has also been implicated is regulating the localization of Anaphase promoting complex/cyclosome (APC/C) to chromosomes. Aurora B kinase has been shown to phosphorylate and regulate kinetochore recruitment of Ska proteins. The Ska complex, in addition to being substrate of Aurora B, also directly activates Aurora B and regulates kinetochore microtubule stability to ensure proper chromosome bi-orientation. The master mitotic kinase Cdk1 phosphorylates Ska3 and regulates Ska complex localization to kinetochores. Cdk1 kinase does not affect spindle localization of the Ska complex suggesting that distinct pathways exist to recruit Ska complex to defined mitotic substructures. Herein we discuss these findings and postulate their implications on Ska complex function during mitosis.    


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