Regulation of SESAME-mediated H3T11 phosphorylation by glycolytic enzymes and metabolites

被引:26
作者
Yu, Qi [1 ]
Tong, Chong [1 ]
Luo, Mingdan [1 ]
Xue, Xiangyan [1 ]
Mei, Qianyun [1 ]
Ma, Lixin [1 ]
Yu, Xiaolan [1 ]
Mao, Wuxiang [1 ]
Kong, Lingbao [2 ,3 ]
Yu, Xilan [1 ]
Li, Shanshan [1 ]
机构
[1] Hubei Univ, Coll Life Sci, Hubei Collaborat Innovat Ctr Green Transformat Bi, Wuhan, Hunan, Peoples R China
[2] Nanchang Univ, Human Aging Res Inst, Dept HumanPopulat Genet, Nanchang, Jiangxi, Peoples R China
[3] Nanchang Univ, Sch Life Sci, Nanchang, Jiangxi, Peoples R China
基金
中国国家自然科学基金;
关键词
PYRUVATE-KINASE; CANCER METABOLISM; HISTONE H3; GENE; SERINE; YEAST; PKM2;
D O I
10.1371/journal.pone.0175576
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Cancer cells prefer aerobic glycolysis, but little is known about the underlying mechanism. Recent studies showed that the rate-limiting glycolytic enzymes, pyruvate kinase M2 (PKM2) directly phosphorylates H3 at threonine 11 (H3T11) to regulate gene expression and cell proliferation, revealing its non-metabolic functions in connecting glycolysis and histone modifications. We have reported that the yeast homolog of PKM2, Pyk1 phosphorylates H3T11 to regulate gene expression and oxidative stress resistance. But how glycolysis regulates H3T11 phosphorylation remains unclear. Here, using a series of glycolytic enzyme mutants and commercial available metabolites, we investigated the role of glycolytic enzymes and metabolites on H3T11 phosphorylation. Mutation of glycolytic genes including phosphoglucose isomerase (PGI1), enolase (ENO2), triosephosphate isomerase (TPI1), or folate biosynthesis enzyme (FOL3) significantly reduced H3T11 phosphorylation. Further study demonstrated that glycolysis regulates H3T11 phosphorylation by fueling the substrate, phosphoenonylpyruvate and the coactivator, FBP to Pyk1. Thus, our results provide a comprehensive view of how glycolysis modulates H3T11 phosphorylation.
引用
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页数:15
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