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

作者：Senese Silvia; Cheung Keith; Lo Yu Chen; Gholkar Ankur A; Xia Xiaoyu; Wohlschlegel James A; Torres Jorge Z^*

来源：Molecular Biology of the Cell, 2015, 26(3): 440-452.

DOI：10.1091/mbc.E14-03-0829

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 similar to 50 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 SCF beta-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 SCF beta-TrCP to promote proper mitotic spindle assembly.

• 出版日期2015-2-1