A unique insertion in STARD9's motor domain regulates its stability.

Mol. Biol. Cell. 2015 Feb 1;26(3):440-52. Epub 2014 Dec 10

Silvia Senese ¹ , Keith Cheung ¹ , Yu-Chen Lo ² , Ankur A Gholkar ¹ , Xiaoyu Xia ¹ ,

Silvia Senese ¹ , Keith Cheung ¹ , Yu-Chen Lo ² , Ankur A Gholkar ¹ , Xiaoyu Xia ¹ , James A Wohlschlegel ³ , Jorge Z Torres ⁴

+ et al

Author information

¹ Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095.
² Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095 Program in Bioengineering, University of California, Los Angeles, Los Angeles, CA 90095.
³ Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095 Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095 Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095.
⁴ Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095 Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095 Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095 torres@chem.ucla.edu.

摘要

STARD9 is a largely uncharacterized mitotic kinesin and putative cancer target that is critical for regulating pericentriolar material cohesion during bipolar spindle assembly. To begin to understand the mechanisms regulating STARD9 function and their importance to cell division, we took a multidisciplinary approach to define the cis and trans factors that regulate the stability of the STARD9 motor domain. We show that, unlike the other â¼50 mammalian kinesins, STARD9 contains an insertion in loop 12 of its motor domain (MD). Working with the STARD9-MD, we show that it is phosphorylated in mitosis by mitotic kinases that include Plk1. These phosphorylation events are important for targeting a pool of STARD9-MD for ubiquitination by the SCFÎ²-TrCP ubiquitin ligase and proteasome-dependent degradation. Of interest, overexpression of nonphosphorylatable/nondegradable STARD9-MD mutants leads to spindle assembly defects. Our results with STARD9-MD imply that in vivo the protein levels of full-length STARD9 could be regulated by Plk1 and SCFÎ²-TrCP to promote proper mitotic spindle assembly.

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基因

PLK1, STARD9

原始数据

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Sample name	Organism	Experiment title	Sample type	Library instrument