The anaphase-promoting complex mediates TGF-beta signaling by targeting SnoN for destruction

Degradation of SnoN is thought to play an important role in the transactiva tion of TGF-P responsive genes. We demonstrate that the anaphase-promoting complex (APC) is a ubiquitin ligase required for the destruction of SnoN an d that the APC pathway is regulated by TGF-beta. The destruction box of Sno N is required for its degradation in response to TGF-P signaling. Furthermo re, the APC activator CDH1 and Smad3 synergistically regulate SnoN degradat ion. Under these circumstances, CDH1 forms a quaternary complex with SnoN, Smad3, and APC. These results suggest that APC(CDH1) and SnoN play central roles in regulating growth through the TGF-beta signaling system.