title: Glyceraldehyde-3-phosphate dehydrogenase is activated by lysine 254 acetylation in response to glucose signal.
abstract: The altered metabolism in most tumor cells consists of elevated glucose uptake and increased glycolysis even in the presence of high oxygen tension. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is an obligatory enzyme in glycolysis. Here, we report that acetylation at lysine 254 (K254) increases GAPDH activity in response to glucose. Furthermore, acetylation of GAPDH (K254) is reversibly regulated by the acetyltransferase PCAF and the deacetylase HDAC5. Substitution of K254 to glutamine compromises the ability of GAPDH to support cell proliferation and tumor growth. Our study reveals a mechanism of GAPDH enzyme activity regulation by acetylation and its critical role in cellular regulation.
authors.affiliation: From the Key Laboratory of Molecular Medicine, Ministry of Education, and Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai 200032, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Li
authors.forename: Mengxi
authors.initials: M
authors.lastname: Liu
authors.forename: Xu
authors.initials: X
authors.lastname: Feng
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.forename: Indrani
authors.initials: I
authors.lastname: Das
authors.forename: Yanping
authors.initials: Y
authors.lastname: Xu
authors.forename: Xin
authors.initials: X
authors.lastname: Zhou
authors.forename: Yiping
authors.initials: Y
authors.lastname: Sun
authors.forename: Kun-Liang
authors.initials: KL
authors.lastname: Guan
authors.forename: Yue
authors.initials: Y
authors.lastname: Xiong
authors.forename: Qun-Ying
authors.initials: QY
authors.lastname: Lei
mesh_terms: D000107:Acetylation; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004789:Enzyme Activation / Q000235:genetics; D005947:Glucose / Q000235:genetics / Q000378:metabolism*; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D015398:Signal Transduction; D050880:p300-CBP Transcription Factors / Q000235:genetics / Q000378:metabolism; D000099224:p300-CBP-Associated Factor
chemical_list: D005947:Glucose; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D006655:Histone Deacetylases; D009363:Neoplasm Proteins; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C404500:HDAC5 protein, human
keywords: Acetylation; Cell Growth; GAPDH; Glycolysis; HDAC5; Histone Deacetylase; Lung Cancer; Metabolism; PCAF; Tumorigenesis