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The E3 ubiquitin ligase TRIM31 is involved in cerebral ischemic injury by promoting degradation of TIGAR
Tripartite motif (TRIM) 31 has been implicated in diverse biological and pathological conditions. However, whether TRIM31 plays a role in ischemic stroke progression is not clarified. Here we demonstrated that TRIM31 was significantly downregulated in the ischemic brain and the deficiency of TRIM31...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260875/ https://www.ncbi.nlm.nih.gov/pubmed/34218200 http://dx.doi.org/10.1016/j.redox.2021.102058 |
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author | Zeng, Shenglan Zhao, Ze Zheng, Shengnan Wu, Mengting Song, Xiaomeng Li, Yiquan Zheng, Yi Liu, Bingyu Chen, Lin Gao, Chengjiang Liu, Huiqing |
author_facet | Zeng, Shenglan Zhao, Ze Zheng, Shengnan Wu, Mengting Song, Xiaomeng Li, Yiquan Zheng, Yi Liu, Bingyu Chen, Lin Gao, Chengjiang Liu, Huiqing |
author_sort | Zeng, Shenglan |
collection | PubMed |
description | Tripartite motif (TRIM) 31 has been implicated in diverse biological and pathological conditions. However, whether TRIM31 plays a role in ischemic stroke progression is not clarified. Here we demonstrated that TRIM31 was significantly downregulated in the ischemic brain and the deficiency of TRIM31 alleviated brain injury induced by middle cerebral artery occlusion by reducing reactive oxygen species production and maintaining mitochondrial homeostasis. Mechanistically, we found that TRIM31 is an E3 ubiquitin ligase for TP53-induced glycolysis and apoptosis regulator (TIGAR), which confers protection against brain ischemia by increasing the pentose phosphate pathway flux and preserving mitochondria function. TRIM31 interacted with TIGAR and promoted the polyubiquitination of TIGAR, consequently facilitated its degradation in a proteasome-dependent pathway. Furthermore, TIGAR knockdown effectively abolished the protective effect of TRIM31 deficiency after cerebral ischemia. In conclusion, we identified that TRIM31 was a novel E3 ubiquitin ligase for TIGAR, played a critical role in regulating its protein level, and subsequently involved in the ischemic brain injury, suggesting TRIM31 as a potential therapeutic target for ischemic stroke. |
format | Online Article Text |
id | pubmed-8260875 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-82608752021-07-12 The E3 ubiquitin ligase TRIM31 is involved in cerebral ischemic injury by promoting degradation of TIGAR Zeng, Shenglan Zhao, Ze Zheng, Shengnan Wu, Mengting Song, Xiaomeng Li, Yiquan Zheng, Yi Liu, Bingyu Chen, Lin Gao, Chengjiang Liu, Huiqing Redox Biol Research Paper Tripartite motif (TRIM) 31 has been implicated in diverse biological and pathological conditions. However, whether TRIM31 plays a role in ischemic stroke progression is not clarified. Here we demonstrated that TRIM31 was significantly downregulated in the ischemic brain and the deficiency of TRIM31 alleviated brain injury induced by middle cerebral artery occlusion by reducing reactive oxygen species production and maintaining mitochondrial homeostasis. Mechanistically, we found that TRIM31 is an E3 ubiquitin ligase for TP53-induced glycolysis and apoptosis regulator (TIGAR), which confers protection against brain ischemia by increasing the pentose phosphate pathway flux and preserving mitochondria function. TRIM31 interacted with TIGAR and promoted the polyubiquitination of TIGAR, consequently facilitated its degradation in a proteasome-dependent pathway. Furthermore, TIGAR knockdown effectively abolished the protective effect of TRIM31 deficiency after cerebral ischemia. In conclusion, we identified that TRIM31 was a novel E3 ubiquitin ligase for TIGAR, played a critical role in regulating its protein level, and subsequently involved in the ischemic brain injury, suggesting TRIM31 as a potential therapeutic target for ischemic stroke. Elsevier 2021-06-29 /pmc/articles/PMC8260875/ /pubmed/34218200 http://dx.doi.org/10.1016/j.redox.2021.102058 Text en © 2021 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research Paper Zeng, Shenglan Zhao, Ze Zheng, Shengnan Wu, Mengting Song, Xiaomeng Li, Yiquan Zheng, Yi Liu, Bingyu Chen, Lin Gao, Chengjiang Liu, Huiqing The E3 ubiquitin ligase TRIM31 is involved in cerebral ischemic injury by promoting degradation of TIGAR |
title | The E3 ubiquitin ligase TRIM31 is involved in cerebral ischemic injury by promoting degradation of TIGAR |
title_full | The E3 ubiquitin ligase TRIM31 is involved in cerebral ischemic injury by promoting degradation of TIGAR |
title_fullStr | The E3 ubiquitin ligase TRIM31 is involved in cerebral ischemic injury by promoting degradation of TIGAR |
title_full_unstemmed | The E3 ubiquitin ligase TRIM31 is involved in cerebral ischemic injury by promoting degradation of TIGAR |
title_short | The E3 ubiquitin ligase TRIM31 is involved in cerebral ischemic injury by promoting degradation of TIGAR |
title_sort | e3 ubiquitin ligase trim31 is involved in cerebral ischemic injury by promoting degradation of tigar |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260875/ https://www.ncbi.nlm.nih.gov/pubmed/34218200 http://dx.doi.org/10.1016/j.redox.2021.102058 |
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