USP26 regulates TGF-β signaling by deubiquitinating and stabilizing SMAD7.

ABSTRACT: The amplitude of transforming growth factor-β (TGF-β) signal is tightly regulated to ensure appropriate physiological responses. As part of negative feedback loop SMAD7, a direct transcriptional target of downstream TGF-β signaling acts as a scaffold to recruit the E3 ligase SMURF2 to target the TGF-β receptor complex for ubiquitin-mediated degradation. Here, we identify the deubiquitinating enzyme USP26 as a novel integral component of this negative feedback loop. We demonstrate that TGF-β rapidly enhances the expression of USP26 and reinforces SMAD7 stability by limiting the ubiquitin-mediated turnover of SMAD7. Conversely, knockdown of USP26 rapidly degrades SMAD7 resulting in TGF-β receptor stabilization and enhanced levels of p-SMAD2. Clinically, loss of USP26 correlates with high TGF

SUBMITTER: Kit Leng Lui S 

PROVIDER: S-EPMC5412796 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature