Please use this identifier to cite or link to this item: https://scholarbank.nus.edu.sg/handle/10635/151859
Title: THE DEUBIQUITINATING ENZYME OTUD4 IS A NOVEL MODULATOR OF TGF? SIGNALING
Authors: JAYNES PATRICK WILLIAM
Keywords: ubiquitin, deubiquitination, DUB, TGFbeta, OTUD4, SMURF2
Issue Date: 23-Aug-2018
Citation: JAYNES PATRICK WILLIAM (2018-08-23). THE DEUBIQUITINATING ENZYME OTUD4 IS A NOVEL MODULATOR OF TGF? SIGNALING. ScholarBank@NUS Repository.
Abstract: Ubiquitination is a post translational modification with wide ranging cellular consequences. Deubiquitinating enzymes (DUBs) function to oppose this modification. The transforming growth factor beta (TGFbeta) pathway plays an important role in development and adult tissue homeostasis and is extensively regulated by ubiquitination. However, the roles of DUBs involved in the regulation of this pathway are not comprehensively known. Through a TGFbeta-responsive luciferase screen depleting all known DUBs, we have identified OTUD4 as a potent modulator of TGFbeta activity. Further biochemical analysis has elucidated that OTUD4 regulates TGFbeta receptor activity via two seemingly independent mechanisms. Firstly, the catalytic activity of this DUB regulates the presence of the TGFbeta receptor complex at the plasma membrane. Secondly, OTUD4 stabilizes TGFbeta receptor II independently of its catalytic activity. In addition, OTUD4 modulates the TGFbeta pathway by facilitating the inactivation of HECT E3 ligase, SMURF2. The resultant consequence of OTUD4 activity is increased TGFbeta signaling.
URI: http://scholarbank.nus.edu.sg/handle/10635/151859
Appears in Collections:Ph.D Theses (Open)

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