Abstract
© 2020, The Author(s). Systematic control of the transforming growth factor-β (TGFβ) 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 TGFβ pathway that functions through a positive feedback loop to enhance overall TGFβ activity. Interestingly we demonstrate that OTUD4 functions through both catalytically dependent and independent mechanisms to regulate TGFβ activity. Specifically, we find that OTUD4 enhances TGFβ signalling by promoting the membrane presence of TGFβ receptor I. Furthermore, we demonstrate that OTUD4 inactivates the TGFβ negative regulator SMURF2 suggesting that OTUD4 regulates multiple nodes of the TGFβ pathway to enhance TGFβ activity.
Keywords
cancer, Deubiquitylating enzymes, Transforming growth factor beta, Ubiquitylation
Document Type
Journal Article
Date of Publication
9-24-2020
Volume
10
Issue
1
PubMed ID
32973272
Publication Title
Scientific Reports
Publisher
Springer Nature
School
School of Medical and Health Sciences
RAS ID
35284
Funders
National Research Foundation Singapore
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Comments
Jaynes, P. W., Iyengar, P. V., Lui, S. K. L., Tan, T. Z., Vasilevski, N., Wright, S. C. E., ... & Eichhorn, P. J. A. (2020). OTUD4 enhances TGFβ signalling through regulation of the TGFβ receptor complex. Scientific Reports, 10(1), Article 15725. https://doi.org/10.1038/s41598-020-72791-0