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 transactivation of TGF-beta 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-beta. The destruction box of SnoN is required for its degradation in response to TGF-beta 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-beta signaling system.
PubMed ID: 11741538
Article link: Mol Cell.
Grant support: GM26875-17 NIGMS NIH HHS , GM39023-08 NIGMS NIH HHS
Genes referenced: cdh1 smad3 tgfb1