OTUD4 enhances TGF? signalling through regulation of the TGF? receptor complex.

ABSTRACT: Systematic control of the transforming growth factor-? (TGF?) pathway is essential to keep the amplitude and the intensity of downstream signalling at appropriate levels. Ubiquitination plays a crucial role in the general regulation of this pathway. Here we identify the deubiquitinating enzyme OTUD4 as a transcriptional target of the TGF? pathway that functions through a positive feedback loop to enhance overall TGF? activity. Interestingly we demonstrate that OTUD4 functions through both catalytically dependent and independent mechanisms to regulate TGF? activity. Specifically, we find that OTUD4 enhances TGF? signalling by promoting the membrane presence of TGF? receptor I. Furthermore, we demonstrate that OTUD4 inactivates the TGF? negative regulator SMURF2 suggesting that OTUD4 regulates multiple nodes of the TGF? pathway to enhance TGF? activity.

SUBMITTER: Jaynes PW 

PROVIDER: S-EPMC7519109 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature