HDAC1 promotes basal autophagy and proliferation of colorectal cancer cells by mediating ATG16L1 deacetylation.

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, 36 Lushan Road, Changsha, Hunan, 410081, China., Zhang 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, 36 Lushan Road, Changsha, Hunan, 410081, China., Liu 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, 36 Lushan Road, Changsha, Hunan, 410081, China., Guo L; 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, 36 Lushan Road, Changsha, Hunan, 410081, 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, 36 Lushan Road, Changsha, Hunan, 410081, 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, 36 Lushan Road, Changsha, Hunan, 410081, 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, 36 Lushan Road, Changsha, Hunan, 410081, China. Electronic address: tingtingli339@hunnu.edu.cn., 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, 36 Lushan Road, Changsha, Hunan, 410081, China. Electronic address: hesp@hunnu.edu.cn.
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2024 Nov 26; Vol. 735, pp. 150667. Date of Electronic Publication: 2024 Sep 07.
DOI: 10.1016/j.bbrc.2024.150667
Abstrakt: Autophagy is an evolutionarily conserved degradation pathway for maintaining cellular homeostasis and its dysregulation leads to numerous human diseases such as cancer. As a core protein for autophagy, ATG16L1 (autophagy related 16 like 1) is heavily regulated by post-translational modifications, including phosphorylation, ubiquitination, and methylation, which is critical for autophagy regulation. In this study, we identify HDAC1 (histone deacetylase 1) as a regulator of ATG16L1 acetylation and hence autophagy. Specifically, HDAC1 colocalizes and interacts with ATG16L1, and reduces its acetylation, which is highly dependent on its enzymatic activity. By promoting ATG16L1 deacetylation, HDAC1 enhances ATG16L1 interaction with the ATG12-ATG5 conjugate, resulting in the activation of autophagic pathway. Consistently, the induction of basal autophagy by HDAC1 in colorectal cancer cells largely relies on its deacetylase activity as well as ATG16L1. Moreover, HDAC1 enhances the survival, proliferation, and transformation of colorectal cancer cells in an ATG16L-dependent manner, indicating the fundamental roles of autophagy in colorectal cancer. Together, our findings uncover a novel regulatory mechanism of autophagy and suggest both HDAC1 and ATG16L1 as therapeutic targets for colorectal cancer.
Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest with the contents of this article.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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