REGγ 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 REGγ, an activator for the 20S proteasome-mediated protein degradation, interacts with Smurf1 and mediates its degradation. We provide evidence that depletion of REGγ stabilizes Smurf1 whereas overexpression of REGγ promotes the degradation of Smurf1. Interestingly both Smurf2 and Smurf1 are destabilized by the REGγ proteasome while the other members of Neural precursor cell-expressed developmentally downregulated gene 4 family were not affected. More importantly, we found that the REGγ proteasome-mediated degradation of Smurf1 results in degradation of Smad5. These findings reveal that the REGγ-proteasome targets a ubiquitin ligase for protein degradation.Structured summaryMINT-7894509: CKIP (uniprotkb:Q53GL0) binds (MI:0407) to Smurf1 (uniprotkb:Q9HCE7) by pull down (MI:0096)MINT-7894494: REG gamma (uniprotkb:P61289) binds (MI:0407) to Smurf1 (uniprotkb:Q9HCE7) by pull down (MI:0096)MINT-7894523, MINT-7894543, MINT-7894481: REG gamma (uniprotkb:P61289) physically interacts (MI:0915) with Smurf1 (uniprotkb:Q9HCE7) by anti tag coimmunoprecipitation (MI:0007)MINT-7894558: Smurf1 (uniprotkb:Q9HCE7) physically interacts (MI:0915) with REG gamma (uniprotkb:P61289) by two hybrid (MI:0018)