OTUD4 enhances TGFβ signalling through regulation of the TGFβ receptor complex
© 2020, The Author(s). Systematic control of the transforming growth factor-β (TGFβ) pathway is essential to keep the amplitude and the intensity of downstream signalling at appropriate levels. Ubiquitination plays a crucial role in the general regulation of this pathway. Here we identify the deubiq...
| Main Authors: | , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
| Published: |
2020
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| Online Access: | http://hdl.handle.net/20.500.11937/81588 |
| _version_ | 1848764390072909824 |
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| author | Jaynes, P.W. Iyengar, P.V. Lui, S.K.L. Tan, T.Z. Vasilevski, Natali Wright, Sarah Christine Elizabeth Verdile, Giuseppe Jeyasekharan, A.D. Eichhorn, Pieter |
| author_facet | Jaynes, P.W. Iyengar, P.V. Lui, S.K.L. Tan, T.Z. Vasilevski, Natali Wright, Sarah Christine Elizabeth Verdile, Giuseppe Jeyasekharan, A.D. Eichhorn, Pieter |
| author_sort | Jaynes, P.W. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | © 2020, The Author(s). Systematic control of the transforming growth factor-β (TGFβ) pathway is essential to keep the amplitude and the intensity of downstream signalling at appropriate levels. Ubiquitination plays a crucial role in the general regulation of this pathway. Here we identify the deubiquitinating enzyme OTUD4 as a transcriptional target of the TGFβ pathway that functions through a positive feedback loop to enhance overall TGFβ activity. Interestingly we demonstrate that OTUD4 functions through both catalytically dependent and independent mechanisms to regulate TGFβ activity. Specifically, we find that OTUD4 enhances TGFβ signalling by promoting the membrane presence of TGFβ receptor I. Furthermore, we demonstrate that OTUD4 inactivates the TGFβ negative regulator SMURF2 suggesting that OTUD4 regulates multiple nodes of the TGFβ pathway to enhance TGFβ activity. |
| first_indexed | 2025-11-14T11:18:35Z |
| format | Journal Article |
| id | curtin-20.500.11937-81588 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| language | eng |
| last_indexed | 2025-11-14T11:18:35Z |
| publishDate | 2020 |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-815882020-11-11T07:03:26Z OTUD4 enhances TGFβ signalling through regulation of the TGFβ receptor complex Jaynes, P.W. Iyengar, P.V. Lui, S.K.L. Tan, T.Z. Vasilevski, Natali Wright, Sarah Christine Elizabeth Verdile, Giuseppe Jeyasekharan, A.D. Eichhorn, Pieter © 2020, The Author(s). Systematic control of the transforming growth factor-β (TGFβ) pathway is essential to keep the amplitude and the intensity of downstream signalling at appropriate levels. Ubiquitination plays a crucial role in the general regulation of this pathway. Here we identify the deubiquitinating enzyme OTUD4 as a transcriptional target of the TGFβ pathway that functions through a positive feedback loop to enhance overall TGFβ activity. Interestingly we demonstrate that OTUD4 functions through both catalytically dependent and independent mechanisms to regulate TGFβ activity. Specifically, we find that OTUD4 enhances TGFβ signalling by promoting the membrane presence of TGFβ receptor I. Furthermore, we demonstrate that OTUD4 inactivates the TGFβ negative regulator SMURF2 suggesting that OTUD4 regulates multiple nodes of the TGFβ pathway to enhance TGFβ activity. 2020 Journal Article http://hdl.handle.net/20.500.11937/81588 10.1038/s41598-020-72791-0 eng http://creativecommons.org/licenses/by/4.0/. fulltext |
| spellingShingle | Jaynes, P.W. Iyengar, P.V. Lui, S.K.L. Tan, T.Z. Vasilevski, Natali Wright, Sarah Christine Elizabeth Verdile, Giuseppe Jeyasekharan, A.D. Eichhorn, Pieter OTUD4 enhances TGFβ signalling through regulation of the TGFβ receptor complex |
| title | OTUD4 enhances TGFβ signalling through regulation of the TGFβ receptor complex |
| title_full | OTUD4 enhances TGFβ signalling through regulation of the TGFβ receptor complex |
| title_fullStr | OTUD4 enhances TGFβ signalling through regulation of the TGFβ receptor complex |
| title_full_unstemmed | OTUD4 enhances TGFβ signalling through regulation of the TGFβ receptor complex |
| title_short | OTUD4 enhances TGFβ signalling through regulation of the TGFβ receptor complex |
| title_sort | otud4 enhances tgfβ signalling through regulation of the tgfβ receptor complex |
| url | http://hdl.handle.net/20.500.11937/81588 |