Regulation of a Spindle Positioning Factor at Kinetochores by SUMO-Targeted Ubiquitin Ligases.

Dev Cell

Centre de Recherche de Biochimie Macromoléculaire (CRBM), CNRS UMR 5237, 1919 route de Mende, 34293 Montpellier Cedex 05, France; Biochemistry Centre Heidelberg (BZH), INF 328, 69120 Heidelberg, Germany; The Hartmut Hoffmann-Berling International Graduate School of Molecular and Cellular Biology, University of Heidelberg, 69117 Heidelberg, Germany. Electronic address:

Published: February 2016

Correct function of the mitotic spindle requires balanced interplay of kinetochore and astral microtubules that mediate chromosome segregation and spindle positioning, respectively. Errors therein can cause severe defects ranging from aneuploidy to developmental disorders. Here, we describe a protein degradation pathway that functionally links astral microtubules to kinetochores via regulation of a microtubule-associated factor. We show that the yeast spindle positioning protein Kar9 localizes not only to astral but also to kinetochore microtubules, where it becomes targeted for proteasomal degradation by the SUMO-targeted ubiquitin ligases (STUbLs) Slx5-Slx8. Intriguingly, this process does not depend on preceding sumoylation of Kar9 but rather requires SUMO-dependent recruitment of STUbLs to kinetochores. Failure to degrade Kar9 leads to defects in both chromosome segregation and spindle positioning. We propose that kinetochores serve as platforms to recruit STUbLs in a SUMO-dependent manner in order to ensure correct spindle function by regulating levels of microtubule-associated proteins.

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http://dx.doi.org/10.1016/j.devcel.2016.01.011DOI Listing

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