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dc.contributor.authorKit Leng Lui, S.
dc.contributor.authorIyengar, P.
dc.contributor.authorJaynes, P.
dc.contributor.authorIsa, Z.
dc.contributor.authorPang, B.
dc.contributor.authorTan, T.
dc.contributor.authorEichhorn, Pieter
dc.identifier.citationKit Leng Lui, S. and Iyengar, P. and Jaynes, P. and Isa, Z. and Pang, B. and Tan, T. and Eichhorn, P. 2017. USP26 regulates TGF-ß signaling by deubiquitinating and stabilizing SMAD7. EMBO Reports. 18 (5): pp. 797-808.

© 2017 The Authors. Published under the terms of the CC BY 4.0 license The amplitude of transforming growth factor-ß (TGF-ß) signal is tightly regulated to ensure appropriate physiological responses. As part of negative feedback loop SMAD7, a direct transcriptional target of downstream TGF-ß signaling acts as a scaffold to recruit the E3 ligase SMURF2 to target the TGF-ß receptor complex for ubiquitin-mediated degradation. Here, we identify the deubiquitinating enzyme USP26 as a novel integral component of this negative feedback loop. We demonstrate that TGF-ß rapidly enhances the expression of USP26 and reinforces SMAD7 stability by limiting the ubiquitin-mediated turnover of SMAD7. Conversely, knockdown of USP26 rapidly degrades SMAD7 resulting in TGF-ß receptor stabilization and enhanced levels of p-SMAD2. Clinically, loss of USP26 correlates with high TGF-ß activity and confers poor prognosis in glioblastoma. Our data identify USP26 as a novel negative regulator of the TGF-ß pathway and suggest that loss of USP26 expression may be an important factor in glioblastoma pathogenesis.

dc.publisherWiley-Blackwell Publishing Ltd.
dc.titleUSP26 regulates TGF-ß signaling by deubiquitinating and stabilizing SMAD7
dc.typeJournal Article
dcterms.source.titleEMBO Reports
curtin.departmentSchool of Pharmacy and Biomedical Sciences
curtin.accessStatusFulltext not available

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