2. Academic Validation
  3. TRAF6 triggers Mycobacterium-infected host autophagy through Rab7 ubiquitination

TRAF6 triggers Mycobacterium-infected host autophagy through Rab7 ubiquitination

  • Cell Death Discov. 2023 Nov 28;9(1):427. doi: 10.1038/s41420-023-01731-4.
Qinmei Ma 1 2,  Jialin Yu 1 2,  Li Liu 1 2,  Xiaoyan Ma 1 2,  Jiaxue Zhang 1 2,  Jiamei Zhang 1 2,  Xiaoping Wang 3,  Guangcun Deng 4 5,  Xiaoling Wu 6 7
Affiliations

Affiliations

  • 1 School of Life Science, Ningxia University, Yinchuan, NingXia, 750021, China.
  • 2 Key Lab of Ministry of Education for Protection and Utilization of Special Biological Resources in Western China, Ningxia University, Yinchuan, NingXia, 750021, China.
  • 3 The Fourth People's Hospital of Ningxia Hui Autonomous Region, Yinchuan, NingXia, 750021, China.
  • 4 School of Life Science, Ningxia University, Yinchuan, NingXia, 750021, China. dgc@nxu.edu.cn.
  • 5 Key Lab of Ministry of Education for Protection and Utilization of Special Biological Resources in Western China, Ningxia University, Yinchuan, NingXia, 750021, China. dgc@nxu.edu.cn.
  • 6 School of Life Science, Ningxia University, Yinchuan, NingXia, 750021, China. wuxiaol@nxu.edu.cn.
  • 7 Key Lab of Ministry of Education for Protection and Utilization of Special Biological Resources in Western China, Ningxia University, Yinchuan, NingXia, 750021, China. wuxiaol@nxu.edu.cn.
PMID: 38016969 DOI: 10.1038/s41420-023-01731-4
Abstract

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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