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TRAF6 triggers Mycobacterium-infected host autophagy through Rab7 ubiquitination

Tumor necrosis factor receptor-associated factor 6 (TRAF6) is an E3 ubiquitin ligase that is extensively involved in the autophagy process by interacting with diverse autophagy initiation and autophagosome maturation molecules. However, whether TRAF6 interacts with lysosomal proteins to regulate Myc...

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Autores principales: Ma, Qinmei, Yu, Jialin, Liu, Li, Ma, Xiaoyan, Zhang, Jiaxue, Zhang, Jiamei, Wang, Xiaoping, Deng, Guangcun, Wu, Xiaoling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10684575/
https://www.ncbi.nlm.nih.gov/pubmed/38016969
http://dx.doi.org/10.1038/s41420-023-01731-4
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author Ma, Qinmei
Yu, Jialin
Liu, Li
Ma, Xiaoyan
Zhang, Jiaxue
Zhang, Jiamei
Wang, Xiaoping
Deng, Guangcun
Wu, Xiaoling
author_facet Ma, Qinmei
Yu, Jialin
Liu, Li
Ma, Xiaoyan
Zhang, Jiaxue
Zhang, Jiamei
Wang, Xiaoping
Deng, Guangcun
Wu, Xiaoling
author_sort Ma, Qinmei
collection PubMed
description Tumor necrosis factor receptor-associated factor 6 (TRAF6) is an E3 ubiquitin ligase that is extensively involved in the autophagy process by interacting with diverse autophagy initiation and autophagosome maturation molecules. However, whether TRAF6 interacts with lysosomal proteins to regulate Mycobacterium-induced autophagy has not been completely characterized. Herein, the present study showed that TRAF6 interacted with lysosomal key proteins Rab7 through RING domain which caused Rab7 ubiquitination and subsequently ubiquitinated Rab7 binds to STX17 (syntaxin 17, a SNARE protein that is essential for mature autophagosome), and thus promoted the fusion of autophagosomes and lysosomes. Furthermore, TRAF6 enhanced the initiation and formation of autophagosomes in Mycobacterium-induced autophagy in both BMDMs and RAW264.7 cells, as evidenced by autophagic flux, colocalization of LC3 and BCG, autophagy rates, and autophagy-associated protein expression. Noteworthy to mention, TRAF6 deficiency exacerbated lung injury and promoted BCG survival. Taken together, these results identify novel molecular and cellular mechanisms by which TRAF6 positively regulates Mycobacterium-induced autophagy.
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spelling pubmed-106845752023-11-30 TRAF6 triggers Mycobacterium-infected host autophagy through Rab7 ubiquitination Ma, Qinmei Yu, Jialin Liu, Li Ma, Xiaoyan Zhang, Jiaxue Zhang, Jiamei Wang, Xiaoping Deng, Guangcun Wu, Xiaoling Cell Death Discov Article Tumor necrosis factor receptor-associated factor 6 (TRAF6) is an E3 ubiquitin ligase that is extensively involved in the autophagy process by interacting with diverse autophagy initiation and autophagosome maturation molecules. However, whether TRAF6 interacts with lysosomal proteins to regulate Mycobacterium-induced autophagy has not been completely characterized. Herein, the present study showed that TRAF6 interacted with lysosomal key proteins Rab7 through RING domain which caused Rab7 ubiquitination and subsequently ubiquitinated Rab7 binds to STX17 (syntaxin 17, a SNARE protein that is essential for mature autophagosome), and thus promoted the fusion of autophagosomes and lysosomes. Furthermore, TRAF6 enhanced the initiation and formation of autophagosomes in Mycobacterium-induced autophagy in both BMDMs and RAW264.7 cells, as evidenced by autophagic flux, colocalization of LC3 and BCG, autophagy rates, and autophagy-associated protein expression. Noteworthy to mention, TRAF6 deficiency exacerbated lung injury and promoted BCG survival. Taken together, these results identify novel molecular and cellular mechanisms by which TRAF6 positively regulates Mycobacterium-induced autophagy. Nature Publishing Group UK 2023-11-28 /pmc/articles/PMC10684575/ /pubmed/38016969 http://dx.doi.org/10.1038/s41420-023-01731-4 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Ma, Qinmei
Yu, Jialin
Liu, Li
Ma, Xiaoyan
Zhang, Jiaxue
Zhang, Jiamei
Wang, Xiaoping
Deng, Guangcun
Wu, Xiaoling
TRAF6 triggers Mycobacterium-infected host autophagy through Rab7 ubiquitination
title TRAF6 triggers Mycobacterium-infected host autophagy through Rab7 ubiquitination
title_full TRAF6 triggers Mycobacterium-infected host autophagy through Rab7 ubiquitination
title_fullStr TRAF6 triggers Mycobacterium-infected host autophagy through Rab7 ubiquitination
title_full_unstemmed TRAF6 triggers Mycobacterium-infected host autophagy through Rab7 ubiquitination
title_short TRAF6 triggers Mycobacterium-infected host autophagy through Rab7 ubiquitination
title_sort traf6 triggers mycobacterium-infected host autophagy through rab7 ubiquitination
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10684575/
https://www.ncbi.nlm.nih.gov/pubmed/38016969
http://dx.doi.org/10.1038/s41420-023-01731-4
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