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https://doi.org/10.1038/srep14733
Title: | USP15 regulates SMURF2 kinetics through C-lobe mediated deubiquitination | Authors: | Iyengar, P.V Jaynes, P Rodon, L Lama, D Law, K.P Lim, Y.P Verma, C Seoane, J Eichhorn, P.J.A |
Keywords: | deubiquitinase lysine SMURF2 protein, human transforming growth factor beta ubiquitin protein ligase USP15 protein, human amino acid sequence cell motion HEK293 cell line human kinetics metabolism physiology protein degradation protein tertiary structure signal transduction ubiquitination Amino Acid Sequence Cell Movement HEK293 Cells Humans Kinetics Lysine Protein Structure, Tertiary Proteolysis Signal Transduction Transforming Growth Factor beta Ubiquitin-Protein Ligases Ubiquitin-Specific Proteases Ubiquitination |
Issue Date: | 2015 | Citation: | Iyengar, P.V, Jaynes, P, Rodon, L, Lama, D, Law, K.P, Lim, Y.P, Verma, C, Seoane, J, Eichhorn, P.J.A (2015). USP15 regulates SMURF2 kinetics through C-lobe mediated deubiquitination. Scientific Reports 5 : 14733. ScholarBank@NUS Repository. https://doi.org/10.1038/srep14733 | 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. | Source Title: | Scientific Reports | URI: | https://scholarbank.nus.edu.sg/handle/10635/175984 | ISSN: | 2045-2322 | DOI: | 10.1038/srep14733 |
Appears in Collections: | Elements Staff Publications |
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