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Regulation of SESAME-mediated H3T11 phosphorylation by glycolytic enzymes and metabolites
Author(s) -
Qingxu Yu,
Chong Wai Tong,
Mingdan Luo,
Xiangyan Xue,
Qianyun Mei,
Lixin Ma,
Xiaohui Yu,
Weihua Mao,
Lingbao Kong,
Xilan Yu,
Shanshan Li
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0175576
Subject(s) - glycolysis , pkm2 , biochemistry , phosphoglycerate mutase , biology , pyruvate kinase , phosphorylation , glucose 6 phosphate isomerase , phosphoglycerate kinase , oxidative phosphorylation , anaerobic glycolysis , aldolase a , triosephosphate isomerase , microbiology and biotechnology , enzyme
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.

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