Document Type

Journal Article

Publication Title

Scientific Reports

Volume

10

Issue

1

PubMed ID

32973272

Publisher

Springer Nature

School

School of Medical and Health Sciences

RAS ID

35284

Funders

National Research Foundation Singapore

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

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.

DOI

10.1038/s41598-020-72791-0

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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