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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.date.accessioned2018-12-13T09:11:44Z
dc.date.available2018-12-13T09:11:44Z
dc.date.created2018-12-12T02:47:06Z
dc.date.issued2017
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.
dc.identifier.urihttp://hdl.handle.net/20.500.11937/71914
dc.identifier.doi10.15252/embr.201643270
dc.description.abstract

© 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.volume18
dcterms.source.number5
dcterms.source.startPage797
dcterms.source.endPage808
dcterms.source.issn1469-221X
dcterms.source.titleEMBO Reports
curtin.departmentSchool of Pharmacy and Biomedical Sciences
curtin.accessStatusFulltext not available


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