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.
Keywords:
Acetylation; Cell Growth; GAPDH; Glycolysis; HDAC5; Histone Deacetylase; Lung Cancer; Metabolism; PCAF; Tumorigenesis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylation
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Animals
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Cell Line, Tumor
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Cell Proliferation*
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Enzyme Activation / genetics
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Glucose / genetics
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Glucose / metabolism*
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Glyceraldehyde-3-Phosphate Dehydrogenases / genetics
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Glyceraldehyde-3-Phosphate Dehydrogenases / metabolism*
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HEK293 Cells
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Histone Deacetylases / genetics
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Histone Deacetylases / metabolism
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Humans
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Mice
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Mice, Inbred BALB C
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Mice, Nude
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Neoplasm Proteins / genetics
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Neoplasm Proteins / metabolism*
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Neoplasms / enzymology*
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Neoplasms / genetics
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Neoplasms / pathology
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Signal Transduction*
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p300-CBP Transcription Factors / genetics
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p300-CBP Transcription Factors / metabolism
Substances
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Neoplasm Proteins
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Glyceraldehyde-3-Phosphate Dehydrogenases
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p300-CBP Transcription Factors
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p300-CBP-associated factor
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HDAC5 protein, human
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Histone Deacetylases
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Glucose