Abstract

Epigenetic mechanisms involved in gene expression play an essential role in various cellular processes, including lipid metabolism. Lysine acetyltransferase 8 (KAT8), a histone acetyltransferase, has been reported to mediate de novo lipogenesis by acetylating fatty acid synthase. However, the effect of KAT8 on lipolysis is unclear. Here, we report a novel mechanism of KAT8 on lipolysis involving in its acetylation by general control non-repressed protein 5 (GCN5) and its deacetylation by Sirtuin 6 (SIRT6). KAT8 acetylation at K168/175 residues attenuates the binding activity of KAT8 and inhibits the recruitment of RNA pol II to the promoter region of the lipolysis-related genes adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL), subsequently down-regulating lipolysis to affect the invasive and migratory potential of colorectal cancer cells. Our findings uncover a novel mechanism that KAT8 acetylation-controlled lipolysis affects invasive and migratory potential in colorectal cancer cells.

Details

Title
KAT8 acetylation-controlled lipolysis affects the invasive and migratory potential of colorectal cancer cells
Author
Qiu, Bingquan 1 ; Li, Shen 2 ; Li, Meiting 1 ; Wang, Shuo 1 ; Mu, Guanqun 1 ; Chen, Keyu 1 ; Wang, Meng 1 ; Zhu, Wei-guo 3 ; Wang, Weibin 4 ; Wang, Jiadong 4 ; Li, Ziyu 2 ; Yang, Jichun 5   VIAFID ORCID Logo  ; Yang, Yang 1   VIAFID ORCID Logo 

1  Peking University Health Science Center, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Department of Biochemistry and Biophysics, School of Basic Medical Sciences, Beijing, China (GRID:grid.11135.37) (ISNI:0000 0001 2256 9319) 
2  Peking University Cancer Hospital & Institute, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery, Beijing, China (GRID:grid.412474.0) (ISNI:0000 0001 0027 0586) 
3  Shenzhen University School of Medicine, Department of Biochemistry and Molecular Biology, Shenzhen, China (GRID:grid.263488.3) (ISNI:0000 0001 0472 9649) 
4  Peking University Health Science Center, Department of Radiation Medicine, Institute of Systems Biomedicine, School of Basic Medical Sciences, Beijing, China (GRID:grid.11135.37) (ISNI:0000 0001 2256 9319) 
5  Peking University Health Science Center, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Science of the Ministry of Education, Center for Non-coding RNA Medicine, Beijing, China (GRID:grid.11135.37) (ISNI:0000 0001 2256 9319) 
Pages
164
Publication year
2023
Publication date
Feb 2023
Publisher
Springer Nature B.V.
e-ISSN
20414889
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41419-023-05582-w
ProQuest document ID
2780269318
Copyright
© The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.