Profiling of HAT1-mediated Lysine Acetylation Modification in Liver Cancer
10.13865/j.cnki.cjbmb.2021.03.1065
- Author:
Hong-Feng YUAN
1
;
Hao-Lin YUN
1
;
Li-Na ZHAO
1
;
Ying YUAN
1
;
Yu GENG
1
;
Lian-Yun FENG
1
;
Yu-Fei WANG
1
;
Xiao-Dong ZHANG
1
;
Xiao-Dong ZHANG
2
;
Guang YANG
Author Information
1. Department of Cancer Research, College of Life Sciences, Nankai University
2. Department of Gastrointestinal Oncobiology, Cancer Institute, Tianjin Medical University Cancer Institute and Hospital
- Publication Type:Journal Article
- Keywords:
histone acetyltransferase 1(HAT1);
lipid metabolism;
liver cancer;
lysine acetylation modification;
protein post-translational modifications(PTM)
- From:
Chinese Journal of Biochemistry and Molecular Biology
2021;37(4):475-486
- CountryChina
- Language:Chinese
-
Abstract:
Lysine acetylation has emerged as one of the most important post-translational modifications that participates in various biological and pathological processes. Histone acetyltransferase 1 (HAT1) as the first identified protein ε-amino lysine acetyltransferase is able to regulate the acetylation of histones and non-histone proteins. However‚ the acetylation substrates and sites mediated by HAT1 in liver cancer are poorly understood. In this study‚ we demonstrated that HAT1 was highly expressed in the liver cancer tissues‚ which was negatively associated with the prognosis of patients. Based on the establishment of the HAT1-knockout HepG2 cell line‚ we employed a quantitative proteomics approach to study the profiling of acetylation mediated by HAT1 in HepG2 cells. Interestingly‚ we identified a total of 858 Kac sites on 547 proteins in the HepG2 cell line‚ in which HAT1 mediated the levels of Kac of 74 sites on 68 proteins. The pathways and metabolic processes that were affected by HAT1-dependent acetylation modification were analyzed by bioinformatics. The results show that Kac regulates disease development‚ RNA biology‚ spliceosome and nucleosome assembly‚ oxidative stress‚ various signaling pathways and metabolic pathways‚ etc.. Moreover‚ we verified that the HAT1-mediated acetylation modification could promote abnormal lipid metabolism. CCK8 assays‚ clone formation and Edu assays revealed that HAT1 could remarkably enhance the cell proliferation of liver cancer in vitro. Thus‚ our finding explored the profiling of HAT1-mediated protein acetylation in HepG2 cells‚ which provides new insights into the underlying mechanism by which HAT1 mediates the development of liver cancer. Clinically‚ the HAT1-mediated acetylation sites could be used for the precise targets of drug development.
