Please use this identifier to cite or link to this item: https://doi.org/10.15252/embr.201643270
Title: USP26 regulates TGF-β signaling by deubiquitinating and stabilizing SMAD7
Authors: Kit Leng Lui, S 
Iyengar, P.V 
Jaynes, P 
Isa, Z.F.B.A 
Pang, B 
Tan, T.Z 
Eichhorn, P.J.A 
Keywords: deubiquitinase
Smad7 protein
transforming growth factor beta
ubiquitin specific protease 26
unclassified drug
cysteine proteinase
deubiquitinase
DNA binding protein
Smad2 protein
SMAD2 protein, human
Smad7 protein
SMAD7 protein, human
SMURF2 protein, human
transactivator protein
transforming growth factor beta
ubiquitin
ubiquitin protein ligase
USP26 protein, human
Article
cancer prognosis
controlled study
glioblastoma
human
human cell
negative feedback
priority journal
protein analysis
protein degradation
protein expression
protein metabolism
protein protein interaction
protein stability
signal transduction
ubiquitination
deficiency
genetics
metabolism
pathophysiology
prognosis
protein processing
signal transduction
Cysteine Endopeptidases
Deubiquitinating Enzymes
DNA-Binding Proteins
Glioblastoma
Humans
Prognosis
Protein Processing, Post-Translational
Signal Transduction
Smad2 Protein
Smad7 Protein
Trans-Activators
Transforming Growth Factor beta
Ubiquitin
Ubiquitin-Protein Ligases
Issue Date: 2017
Publisher: Wiley-VCH Verlag
Citation: Kit Leng Lui, S, Iyengar, P.V, Jaynes, P, Isa, Z.F.B.A, Pang, B, Tan, T.Z, Eichhorn, P.J.A (2017). USP26 regulates TGF-β signaling by deubiquitinating and stabilizing SMAD7. EMBO Reports 18 (5) : 797-808. ScholarBank@NUS Repository. https://doi.org/10.15252/embr.201643270
Abstract: The amplitude of transforming growth factor-β (TGF-β) signal is tightly regulated to ensure appropriate physiological responses. As part of negative feedback loop SMAD7, a direct transcriptional target of downstream TGF-β signaling acts as a scaffold to recruit the E3 ligase SMURF2 to target the TGF-β 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-? 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-β receptor stabilization and enhanced levels of p-SMAD2. Clinically, loss of USP26 correlates with high TGF-β activity and confers poor prognosis in glioblastoma. Our data identify USP26 as a novel negative regulator of the TGF-β pathway and suggest that loss of USP26 expression may be an important factor in glioblastoma pathogenesis. © 2017 The Authors. Published under the terms of the CC BY 4.0 license
Source Title: EMBO Reports
URI: https://scholarbank.nus.edu.sg/handle/10635/173847
ISSN: 1469221X
DOI: 10.15252/embr.201643270
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