The role of Anaphase-Promoting Co mplex(APC)Activator Cdh1 on cell motility

Cdh 1是后期促进复合物/环体的激活剂，并通过靶向细胞周期蛋白进行降解来促进有丝分裂退出和G1期维持。在这里，我们发现了Cdh 1作为Rho调节剂的新功能。GTP结合的活性Rho蛋白在Cdh 1缺失的细胞中明显减少。Cdh 1与p190蛋白（Rho的主要GAP）形成物理复合物，并在体外和体内刺激p190的有效泛素化。Cdh 1耗尽细胞的运动性受损，然而，共同耗尽p190拯救了这些细胞的迁移活性。此外，纯合Cdh 1基因捕获的小鼠胚胎表现出类似的表型Rho相关激酶I和II基因敲除小鼠观察到的，这表明Cdh 1/p190/Rho轴在体内的意义。

Cdh1 is an activator of the anaphase-promoting complex/cyclosome and contributes to mitotic exit and G1 maintenance by targeting cell-cycle proteins for degradation. Here, we found a novel function for Cdh1 as a regulator of Rho. The GTP-bound active Rho protein was apparently decreased in the Cdh1-depleted cells. Cdh1 formed a physical complex with the p190 protein, a major GAP for Rho, and stimulated the efficient ubiquitination of p190, both in in vitro and in vivo. The motility of Cdh1-depleted cells was impaired ; however, co-depletion of p190 rescued the migration activity of these cells. Moreover, homozygous Cdh1 gene-trapped mouse embryos exhibited similar phenotypes to those observed for Rho-associated kinase I and II knockout mice, suggesting the in vivo significance of Cdh1/p190/Rho axis.