REGgamma proteasome mediates degradation of the ubiquitin ligase Smurf1.

The ubiquitin ligase Smad ubiquitination regulatory factor 1 (Smurf1) targets many proteins including Smad1/5 for ubiquitin-dependent proteasomal degradation. However, how Smurf1 is degraded remains unclear. Here we show that REGgamma, an activator for the 20S proteasome-mediated protein degradation, interacts with Smurf1 and mediates its degradation. We provide evidence that depletion of REGgamma stabilizes Smurf1 whereas overexpression of REGgamma promotes the degradation of Smurf1. Interestingly both Smurf2 and Smurf1 are destabilized by the REGgamma proteasome while the other members of Neural precursor cell-expressed developmentally downregulated gene 4 family were not affected. More importantly, we found that the REGgamma proteasome-mediated degradation of Smurf1 results in degradation of Smad5. These findings reveal that the REGgamma-proteasome targets a ubiquitin ligase for protein degradation. Copyright 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.