The Anaphase-Promoting Complex Mediates TGF-β Signaling by Targeting SnoN for Destruction

Abstract

Degradation of SnoN is thought to play an important role in the transactivation of TGF-β responsive genes. We demonstrate that the anaphase-promoting complex (APC) is a ubiquitin ligase required for the destruction of SnoN and that the APC pathway is regulated by TGF-β. The destruction box of SnoN is required for its degradation in response to TGF-β signaling. Furthermore, the APC activator CDH1 and Smad3 synergistically regulate SnoN degradation. 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-β signaling system.