HSP70 promotes amino acid-dependent mTORC1 signaling by mediating CHIP-induced NPRL2 ubiquitination and degradation.

Autor:	Gao J; Hunan Provincial Key Laboratory of Animal Intestinal Function and Regulation, Hunan International Joint Laboratory of Animal Intestinal Ecology and Health, School of Life Sciences, Hunan Normal University, Changsha, Hunan, China., Lin M; Hunan Provincial Key Laboratory of Animal Intestinal Function and Regulation, Hunan International Joint Laboratory of Animal Intestinal Ecology and Health, School of Life Sciences, Hunan Normal University, Changsha, Hunan, China., Qing J; Hunan Provincial Key Laboratory of Animal Intestinal Function and Regulation, Hunan International Joint Laboratory of Animal Intestinal Ecology and Health, School of Life Sciences, Hunan Normal University, Changsha, Hunan, China., Li H; Hunan Provincial Key Laboratory of Animal Intestinal Function and Regulation, Hunan International Joint Laboratory of Animal Intestinal Ecology and Health, School of Life Sciences, Hunan Normal University, Changsha, Hunan, China., Zeng X; Hunan Provincial Key Laboratory of Animal Intestinal Function and Regulation, Hunan International Joint Laboratory of Animal Intestinal Ecology and Health, School of Life Sciences, Hunan Normal University, Changsha, Hunan, China., Yuan W; Hunan Provincial Key Laboratory of Animal Intestinal Function and Regulation, Hunan International Joint Laboratory of Animal Intestinal Ecology and Health, School of Life Sciences, Hunan Normal University, Changsha, Hunan, China., Li T; Hunan Provincial Key Laboratory of Animal Intestinal Function and Regulation, Hunan International Joint Laboratory of Animal Intestinal Ecology and Health, School of Life Sciences, Hunan Normal University, Changsha, Hunan, China., He S; Hunan Provincial Key Laboratory of Animal Intestinal Function and Regulation, Hunan International Joint Laboratory of Animal Intestinal Ecology and Health, School of Life Sciences, Hunan Normal University, Changsha, Hunan, China.
Jazyk:	angličtina
Zdroj:	FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2024 Nov 15; Vol. 38 (21), pp. e70147.
DOI:	10.1096/fj.202401352R
Abstrakt:	Mechanistic target of rapamycin complex 1 (mTORC1) is a master regulator of cell growth and its dysregulation leads to a variety of human diseases. Although NPRL2, an essential component of the GATOR1 complex, is reported to effectively suppress amino acid-induced mTORC1 activation, the regulation of NPRL2 protein stability is unclear. In this study, we show that chaperon-associated ubiquitin ligase CHIP interacts with NPRL2 and promotes its polyubiquitination and proteasomal degradation. Moreover, HSP70 mediates CHIP-induced ubiquitination and degradation of NPRL2. Consistently, overexpression of HSP70 enhances whereas HSP70 depletion inhibits amino acid-induced mTORC1 activation. Accordingly, knockdown of HSP70 promotes basal autophagic flux, and inhibits cell growth and proliferation. Taken together, these results demonstrated that HSP70 is a novel activator of mTORC1 through mediating CHIP-induced ubiquitination and degradation of NPRL2. (© 2024 Federation of American Societies for Experimental Biology.)
Databáze:	MEDLINE
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