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Title: USP15 regulates SMURF2 kinetics through C-lobe mediated deubiquitination
Authors: Iyengar, Prasanna Vasudevan
Jaynes, Patrick
Rodon, Laura
Lama, Dilraj
Law, Kai Pong
Lim, Yoon Pin
Verma, Chandra
Seoane, Joan
Eichhorn, Pieter Johan Adam
Issue Date: 2015
Source: Iyengar, P. V., Jaynes, P., Rodon, L., Lama, D., Law, K. P., Lim, Y. P., et al. (2015). USP15 regulates SMURF2 kinetics through C-lobe mediated deubiquitination. Scientific Reports, 5, 14733-.
Series/Report no.: Scientific Reports
Abstract: Ubiquitin modification of the TGF-β pathway components is emerging as a key mechanism of TGF-β pathway regulation. To limit TGF-β responses, TGF-β signaling is regulated through a negative feedback loop whereby the E3 ligase SMURF2 targets the TGF-β receptor (TβR) complex for ubiquitin-mediated degradation. Counteracting this process, a number of deubiquitinating (DUBs) enzymes have recently been identified that deubiquitinate and stabilize the TβR. However the precise mechanism by which these DUBs act on TβR function remains poorly defined. Here, we demonstrate that apart from targeting the TβR complex directly, USP15 also deubiquitinates SMURF2 resulting in enhanced TβR stability and downstream pathway activation. Through proteomic analysis, we show that USP15 modulates the ubiquitination of Lys734, a residue required for SMURF2 catalytic activity. Our results show that SMURF2 is a critical target of USP15 in the TGF-β pathway and may also explain how USP15 and SMURF2 target multiple complementary protein complexes in other pathways.
ISSN: 2045-2322
DOI: 10.1038/srep14733
Schools: School of Biological Sciences 
Rights: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

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