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

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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.