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

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

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

机译：组蛋白乙酰转移酶1是组蛋白和非组蛋白的琥珀酰转移酶，并促进肿瘤发生

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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.

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来源
《EMBO reports》 |2021年第2期|共18页
作者
Yang Guang; Yuan Ying; Yuan Hongfeng; Wang Jiapei; Yun Haolin; Geng Yu; Zhao Man; Li Linhan; Weng Yejing; Liu Zixian; Feng Jinyan; Bu Yanan; Liu Lei; Wang Bingnan; Zhang Xiaodong;
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作者单位

Nankai Univ Coll Life Sci Inst Mol Biol Dept Canc Res Tianjin Peoples R China;

Nankai Univ Coll Life Sci Inst Mol Biol Dept Canc Res Tianjin Peoples R China;

Nankai Univ Coll Life Sci Inst Mol Biol Dept Canc Res Tianjin Peoples R China;

Nankai Univ Coll Life Sci Inst Mol Biol Dept Canc Res Tianjin Peoples R China;

Nankai Univ Coll Life Sci Inst Mol Biol Dept Canc Res Tianjin Peoples R China;

Nankai Univ Coll Life Sci Inst Mol Biol Dept Canc Res Tianjin Peoples R China;

Nankai Univ Coll Life Sci Inst Mol Biol Dept Canc Res Tianjin Peoples R China;

Jingjie PTM BioLab Co Ltd Hangzhou Econ &

Technol Dev Area Hangzhou Peoples R China;

Jingjie PTM BioLab Co Ltd Hangzhou Econ &

Technol Dev Area Hangzhou Peoples R China;

Nankai Univ Coll Life Sci Inst Mol Biol Dept Canc Res Tianjin Peoples R China;

Nankai Univ Coll Life Sci Inst Mol Biol Dept Canc Res Tianjin Peoples R China;

Nankai Univ Coll Life Sci Inst Mol Biol Dept Canc Res Tianjin Peoples R China;

Nankai Univ Coll Life Sci Inst Mol Biol Dept Canc Res Tianjin Peoples R China;

Jingjie PTM BioLab Co Ltd Hangzhou Econ &

Technol Dev Area Hangzhou Peoples R China;

Nankai Univ Coll Life Sci Inst Mol Biol Dept Canc Res Tianjin Peoples R China;

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原文格式 PDF
正文语种 eng
中图分类分子生物学;
关键词
epigenetic regulation; glycolysis; HAT1; succinylation; tumorigenesis;

机译：表观遗传调节;糖酵解;帽子1;琥珀酰化;肿瘤发生;

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专利

1. Biological function and regulation of histone and non-histone lysine methylation in response to DNA damage [J] . Yongcan Chen, Wei-Guo Zhu 生物化学与生物物理学报：英文版 . 2016,第007期
2. Histone acetyltransferase p300 promotes MKL1-mediated transactivation of catechol-O-methyltransferase gene [J] . Zhipeng Liu, Xuegang Luo, Lei Liu, 生物化学与生物物理学报：英文版 . 2013,第012期
3. Global profiling of crotonylation on non-histone proteins [J] . Weizhi Xu, Junhu Wan, Jun Zhan, 细胞研究（英文版） . 2017,第007期
4. Histone acetyltransferase hMOF promotes S phase entry and tumorigenesis in lung cancer [J] . Zhao L., Wang D.-L., Liu Y., Cellular Signalling . 2013,第8期

机译：组蛋白乙酰转移酶hMOF促进肺癌的S期进入和肿瘤发生
5. The isolation, characterization and partial sequence of a peptide rich in glutamic acid and aspartic acid (HGA-2 peptide) from calf thymus non-histone chromosomal protein HMG 2. Comparison with a similar peptide (HGA-1 peptide) from calf thymus non-histone chromosomal protein HMG 1 [J] . E W Johns, J M Walker, K Gooderham The biochemical journal . 1979,第1期

机译：小牛胸腺非组蛋白染色体蛋白HMG 2中富含谷氨酸和天冬氨酸的肽（HGA-2肽）的分离，表征和部分序列。组蛋白染色体蛋白HMG 1
6. The isolation and partial sequence of peptides produced by cyanogen bromide cleavage of calf thymus non-histone chromosomal high-mobility-group protein 2. Sequence homology with non-histone chromosomal high-mobility-group protein 1 [J] . E W Johns, J M Walker, K Gooderham The biochemical journal . 1979,第3期

机译：小牛胸腺非组蛋白染色体高迁移率蛋白2的溴化氰裂解产生的肽的分离和部分序列。与非组蛋白染色体高迁移率蛋白1的序列同源性。
7. Investigating the specificity of histone acetyltransferase activity for producing rare modifications on histones using mass spectrometry [C] . Amanda Hu, Laura-Mae Britton, Benjamin A. Garcia ASMS Conference on Mass Spectrometry and Allied Topics . 2014

机译：研究组氨酸乙酰转移酶活性的特异性，使用质谱法在组蛋白上产生罕见修饰
8. Functional characterization of the regulation of transcription factor MEF2C by histone acetyltransferase p300 and histone deacetylase 4. [D] . Chan, Jonathan Ka Lok. 2004

机译：组蛋白乙酰转移酶p300和组蛋白脱乙酰基酶4对转录因子MEF2C调控的功能表征。
9. The isolation characterization and partial sequence of a peptide rich in glutamic acid and aspartic acid (HGA-2 peptide) from calf thymus non-histone chromosomal protein HMG 2. Comparison with a similar peptide (HGA-1 peptide) from calf thymus non-histone chromosomal protein HMG 1. [O] . J M Walker, K Gooderham, E W Johns 1979

机译：小牛胸腺非组蛋白染色体蛋白HMG 2中富含谷氨酸和天冬氨酸的肽（HGA-2肽）的分离表征和部分序列与非小牛胸腺的类似肽（HGA-1肽）的比较组蛋白染色体蛋白HMG 1。
10. The isolation, characterization and partial sequence of a peptide rich in glutamic acid and aspartic acid (HGA-2 peptide) from calf thymus non-histone chromosomal protein HMG 2. Comparison with a similar peptide (HGA-1 peptide) from calf thymus non-histone chromosomal protein HMG 1. [O] . Walker, J M, Gooderham, K, Johns, E W 1979

机译：小牛胸腺非组蛋白染色体蛋白HMG 2中富含谷氨酸和天冬氨酸的肽（HGA-2肽）的分离，表征和部分序列与非小牛胸腺的类似肽（HGA-1肽）的比较组蛋白染色体蛋白HMG 1。
11. Study of the Non-Histone Proteins of the Nucleo-Chromatin Complex. Progress Report, May 1978-September 1979. [R] . Patel, G. L. 1979

机译：核染色质复合物非组蛋白的研究。进展报告，1978年5月至1979年9月。

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

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