Histone acetyltransferase 1 is a succinyltransferase for histones and non-histones and promotes tumorigenesis.

Guang Yang, Ying Yuan, Hongfeng Yuan, Jiapei Wang, Haolin Yun, Yu Geng, Man Zhao, Linhan Li, Yejing Weng, Zixian Liu, Jinyan Feng, Yanan Bu, Lei Liu, Bingnan Wang, Xiaodong Zhang

EMBO reports 2021 Feb 03

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Lysine succinylation (Ksucc) is an evolutionarily conserved and widespread post-translational modification. Histone acetyltransferase 1 (HAT1) is a type B histone acetyltransferase, regulating the acetylation of both histone and non-histone proteins. However, the role of HAT1 in succinylation modulation remains unclear. Here, we employ a quantitative proteomics approach to study succinylation in HepG2 cancer cells and find that HAT1 modulates lysine succinylation on various proteins including histones and non-histones. HAT1 succinylates histone H3 on K122, contributing to epigenetic regulation and gene expression in cancer cells. Moreover, HAT1 catalyzes the succinylation of PGAM1 on K99, resulting in its increased enzymatic activity and the stimulation of glycolytic flux in cancer cells. Clinically, HAT1 is significantly elevated in liver cancer, pancreatic cancer, and cholangiocarcinoma tissues. Functionally, HAT1 succinyltransferase activity and the succinylation of PGAM1 by HAT1 play critical roles in promoting tumor progression in vitro and in vivo. Thus, we conclude that HAT1 is a succinyltransferase for histones and non-histones in tumorigenesis. © 2020 The Authors.

Citation

Guang Yang, Ying Yuan, Hongfeng Yuan, Jiapei Wang, Haolin Yun, Yu Geng, Man Zhao, Linhan Li, Yejing Weng, Zixian Liu, Jinyan Feng, Yanan Bu, Lei Liu, Bingnan Wang, Xiaodong Zhang. Histone acetyltransferase 1 is a succinyltransferase for histones and non-histones and promotes tumorigenesis. EMBO reports. 2021 Feb 03;22(2):e50967