한빛사논문
- 조회631
Yan Gao 1, Xinlei Sheng 2, Doudou Tan 3, SunJoo Kim 1,2, Soyoung Choi 1, Sanjita Paudel 1, Taeho Lee 1, Cong Yan 3, Minjia Tan 3, Kyu Min Kim 4, Sam Seok Cho 5, Sung Hwan Ki 5, He Huang 3,6, Yingming Zhao 2, Sangkyu Lee 7
1College of Pharmacy, Kyungpook National University, Daegu, 41566, Republic of Korea.
2Ben May Department for Cancer Research, The University of Chicago, Chicago, IL, 60637, USA.
3Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
4Department of Biomedical Science, College of Natural Science, Chosun University, Gwangju, 61452, South Korea.
5College of Pharmacy, Chosun University, Gwangju, 61452, South Korea.
6University of Chinese Academy of Sciences, Beijing, 100049, China.
7School of Pharmacy, Sungkyunkwan University, Suwon, 16419, South Korea.
Y.G., X.S., D.T., and S.K. contributed equally to this work.
CORRESPONDING AUTHORS: He Huang, Yingming Zhao, Sangkyu Lee
Abstract
Ketone bodies have long been known as a group of lipid-derived alternative energy sources during glucose shortages. Nevertheless, the molecular mechanisms underlying their non-metabolic functions remain largely elusive. This study identified acetoacetate as the precursor for lysine acetoacetylation (Kacac), a previously uncharacterized and evolutionarily conserved histone post-translational modification. This protein modification is comprehensively validated using chemical and biochemical approaches, including HPLC co-elution and MS/MS analysis using synthetic peptides, Western blot, and isotopic labeling. Histone Kacac can be dynamically regulated by acetoacetate concentration, possibly via acetoacetyl-CoA. Biochemical studies show that HBO1, traditionally known as an acetyltransferase, can also serve as an acetoacetyltransferase. In addition, 33 Kacac sites are identified on mammalian histones, depicting the landscape of histone Kacac marks across species and organs. In summary, this study thus discovers a physiologically relevant and enzymatically regulated histone mark that sheds light on the non-metabolic functions of ketone bodies.
논문정보
- Research article
- 2023년 06월 (BRIC 등록일 2023-07-17)
- 국내(교신)+국외 연구진
- 의약학 > 약학
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