title: Deacetylation of phosphoglycerate mutase in its distinct central region by SIRT2 down-regulates its enzymatic activity.
abstract: Substantially high rate of glycolysis, known as the Warburg effect, is a well-known feature of cancers, and emerging evidence suggests that it supports cancerous proliferation/tumor growth. Phosphoglycerate mutase (PGAM), a glycolytic enzyme, is commonly up-regulated in several cancers, and recent reports show its involvement in the Warburg effect. Here, a comprehensive analysis shows that PGAM is acetylated at lysines 100/106/113/138 in its central region, and a member of the Sirtuin family (class III deacetylase), SIRT2, is responsible for its deacetylation. Over-expression of SIRT2 or mutations at the acetylatable lysines of PGAM attenuates cancer cell proliferation with a concomitant decrease in PGAM activity. We also report that the acetyltransferase PCAF (p300/CBP-associated factor) interacts with PGAM and acetylates its C-terminus, but not the central region. As prior evidence suggests that SIRT2 functions as a tumor suppressor, our results would provide support for the mechanistic basis of this activity.
authors.affiliation: Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tsusaka
authors.forename: Tingting
authors.initials: T
authors.lastname: Guo
authors.forename: Teiti
authors.initials: T
authors.lastname: Yagura
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Inoue
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yokode
authors.forename: Nobuya
authors.initials: N
authors.lastname: Inagaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kondoh
mesh_terms: D000107:Acetylation; D000818:Animals; D001120:Arginine / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D006801:Humans; D008239:Lysine / Q000378:metabolism; D051379:Mice; D009154:Mutation; D010736:Phosphoglycerate Mutase / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D056565:Sirtuin 2 / Q000235:genetics / Q000378:metabolism*; D037761:Sirtuins / Q000378:metabolism; D050880:p300-CBP Transcription Factors / Q000378:metabolism*; D000099224:p300-CBP-Associated Factor
chemical_list: D001120:Arginine; D008239:Lysine; D010736:Phosphoglycerate Mutase; D056565:Sirtuin 2; D037761:Sirtuins; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C474199:SIRT2 protein, human