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 APCCDH1 and SnoN play central roles in regulating growth through the TGF-β signaling system.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1027-1039 |
| Number of pages | 13 |
| Journal | Molecular cell |
| Volume | 8 |
| Issue number | 5 |
| DOIs | |
| State | Published - Nov 21 2001 |
Funding
We are grateful to the members of the Kirschner lab for their excellent advice and critical discussions, especially N. Ayad, O. Stemmann, and H. Zou. Dominant-negative CDH1 and carboxy-terminal CDH1(D173) plasmids were generously provided by Cathie M. Pfleger. The pCS2-Flag-Smad3 and pCS2-ALK3*HA were a kind gift from Malcolm Whitman. We thank Kunxin Luo for providing her manuscript in advance of publication. Y.W. is a Helen Hay Whitney fellow. This work is supported by grants GM26875-17 and GM39023-08 from the National Institutes of Health to M.W.K.
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology