Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Zeng, Shenglan, Zhao, Ze, Zheng, Shengnan, Wu, Mengting, Song, Xiaomeng, Li, Yiquan, Zheng, Yi, Liu, Bingyu, Chen, Lin, Gao, Chengjiang, Liu, Huiqing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
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
_version_ 1783718901372157952
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
work_keys_str_mv AT zengshenglan thee3ubiquitinligasetrim31isinvolvedincerebralischemicinjurybypromotingdegradationoftigar
AT zhaoze thee3ubiquitinligasetrim31isinvolvedincerebralischemicinjurybypromotingdegradationoftigar
AT zhengshengnan thee3ubiquitinligasetrim31isinvolvedincerebralischemicinjurybypromotingdegradationoftigar
AT wumengting thee3ubiquitinligasetrim31isinvolvedincerebralischemicinjurybypromotingdegradationoftigar
AT songxiaomeng thee3ubiquitinligasetrim31isinvolvedincerebralischemicinjurybypromotingdegradationoftigar
AT liyiquan thee3ubiquitinligasetrim31isinvolvedincerebralischemicinjurybypromotingdegradationoftigar
AT zhengyi thee3ubiquitinligasetrim31isinvolvedincerebralischemicinjurybypromotingdegradationoftigar
AT liubingyu thee3ubiquitinligasetrim31isinvolvedincerebralischemicinjurybypromotingdegradationoftigar
AT chenlin thee3ubiquitinligasetrim31isinvolvedincerebralischemicinjurybypromotingdegradationoftigar
AT gaochengjiang thee3ubiquitinligasetrim31isinvolvedincerebralischemicinjurybypromotingdegradationoftigar
AT liuhuiqing thee3ubiquitinligasetrim31isinvolvedincerebralischemicinjurybypromotingdegradationoftigar
AT zengshenglan e3ubiquitinligasetrim31isinvolvedincerebralischemicinjurybypromotingdegradationoftigar
AT zhaoze e3ubiquitinligasetrim31isinvolvedincerebralischemicinjurybypromotingdegradationoftigar
AT zhengshengnan e3ubiquitinligasetrim31isinvolvedincerebralischemicinjurybypromotingdegradationoftigar
AT wumengting e3ubiquitinligasetrim31isinvolvedincerebralischemicinjurybypromotingdegradationoftigar
AT songxiaomeng e3ubiquitinligasetrim31isinvolvedincerebralischemicinjurybypromotingdegradationoftigar
AT liyiquan e3ubiquitinligasetrim31isinvolvedincerebralischemicinjurybypromotingdegradationoftigar
AT zhengyi e3ubiquitinligasetrim31isinvolvedincerebralischemicinjurybypromotingdegradationoftigar
AT liubingyu e3ubiquitinligasetrim31isinvolvedincerebralischemicinjurybypromotingdegradationoftigar
AT chenlin e3ubiquitinligasetrim31isinvolvedincerebralischemicinjurybypromotingdegradationoftigar
AT gaochengjiang e3ubiquitinligasetrim31isinvolvedincerebralischemicinjurybypromotingdegradationoftigar
AT liuhuiqing e3ubiquitinligasetrim31isinvolvedincerebralischemicinjurybypromotingdegradationoftigar