Mitotic Regulation of the Stability of Microtubule Plus-end Tracking Protein EB3 by Ubiquitin Ligase SIAH-1 and Aurora Mitotic Kinases

作者：Ban Reiko^*; Matsuzaki Hideki; Akashi Tomohiro; Sakashita Gyosuke; Taniguchi Hisaaki; Park Sam Yong; Tanaka Hirofumi; Furukawa Koichi; Urano Takeshi

来源：Journal of Biological Chemistry, 2009, 284(41): 28367-28381.

DOI：10.1074/jbc.M109.000273

Microtubule plus-end tracking proteins ( TIPs) control microtubule dynamics in fundamental processes such as cell cycle, intracellular transport, and cell motility, but how TIPs are regulated during mitosis remains largely unclear. Here we show that the endogenous end-binding protein family EB3 is stable during mitosis, facilitates cell cycle progression at prometaphase, and then is down-regulated during the transition to G, phase. The ubiquitin-protein isopeptide ligase SIAH-1 facilitates EB3 polyubiquitination and subsequent proteasome-mediated degradation, whereas SIAH-1 knockdown increases EB3 stability and steady-state levels. Two mitotic kinases, Aurora-A and Aurora-B, phosphorylate endogenous EB3 at Ser-176, and the phosphorylation triggers disruption of the EB3-SIAH-1 complex, resulting in EB3 stabilization during mitosis. Our results provide new insight into a regulatory mechanism of TIPs in cell cycle transition.

• 出版日期2009-10-9