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    USP26 regulates TGF-ß signaling by deubiquitinating and stabilizing SMAD7

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    Fulltext not available
    Authors
    Kit Leng Lui, S.
    Iyengar, P.
    Jaynes, P.
    Isa, Z.
    Pang, B.
    Tan, T.
    Eichhorn, Pieter
    Date
    2017
    Type
    Journal Article
    
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    Citation
    Kit 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.
    Source Title
    EMBO Reports
    DOI
    10.15252/embr.201643270
    ISSN
    1469-221X
    School
    School of Pharmacy and Biomedical Sciences
    URI
    http://hdl.handle.net/20.500.11937/71914
    Collection
    • Curtin Research Publications
    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.

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