USP26 regulates TGF-ß signaling by deubiquitinating and stabilizing SMAD7
© 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 signali...
| Main Authors: | , , , , , , |
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| Format: | Journal Article |
| Published: |
Wiley-Blackwell Publishing Ltd.
2017
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| Online Access: | http://hdl.handle.net/20.500.11937/71914 |
| _version_ | 1848762608224567296 |
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| author | Kit Leng Lui, S. Iyengar, P. Jaynes, P. Isa, Z. Pang, B. Tan, T. Eichhorn, Pieter |
| author_facet | Kit Leng Lui, S. Iyengar, P. Jaynes, P. Isa, Z. Pang, B. Tan, T. Eichhorn, Pieter |
| author_sort | Kit Leng Lui, S. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | © 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. |
| first_indexed | 2025-11-14T10:50:16Z |
| format | Journal Article |
| id | curtin-20.500.11937-71914 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T10:50:16Z |
| publishDate | 2017 |
| publisher | Wiley-Blackwell Publishing Ltd. |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-719142020-06-01T23:46:48Z USP26 regulates TGF-ß signaling by deubiquitinating and stabilizing SMAD7 Kit Leng Lui, S. Iyengar, P. Jaynes, P. Isa, Z. Pang, B. Tan, T. Eichhorn, Pieter © 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. 2017 Journal Article http://hdl.handle.net/20.500.11937/71914 10.15252/embr.201643270 Wiley-Blackwell Publishing Ltd. restricted |
| spellingShingle | Kit Leng Lui, S. Iyengar, P. Jaynes, P. Isa, Z. Pang, B. Tan, T. Eichhorn, Pieter USP26 regulates TGF-ß signaling by deubiquitinating and stabilizing SMAD7 |
| title | USP26 regulates TGF-ß signaling by deubiquitinating and stabilizing SMAD7 |
| title_full | USP26 regulates TGF-ß signaling by deubiquitinating and stabilizing SMAD7 |
| title_fullStr | USP26 regulates TGF-ß signaling by deubiquitinating and stabilizing SMAD7 |
| title_full_unstemmed | USP26 regulates TGF-ß signaling by deubiquitinating and stabilizing SMAD7 |
| title_short | USP26 regulates TGF-ß signaling by deubiquitinating and stabilizing SMAD7 |
| title_sort | usp26 regulates tgf-ß signaling by deubiquitinating and stabilizing smad7 |
| url | http://hdl.handle.net/20.500.11937/71914 |