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: Tingting Li, Mengxi Liu, Xu Feng, Zhen Wang, Indrani Das, Yanping Xu, Xin Zhou, Yiping Sun, Kun-Liang Guan, Yue Xiong, Qun-Ying Lei
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 289 Issue 6 Pg. 3775-85 (Feb 07 2014) ISSN: 1083-351X [Electronic] United States
• PMID: 24362262 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Neoplasm Proteins
• Glyceraldehyde-3-Phosphate Dehydrogenases
• p300-CBP Transcription Factors
• p300-CBP-associated factor
• HDAC5 protein, human
• Histone Deacetylases
• Glucose

Topics

• Acetylation
• Animals
• Cell Line, Tumor
• Cell Proliferation
• Enzyme Activation (genetics)
• Glucose (genetics, metabolism)
• Glyceraldehyde-3-Phosphate Dehydrogenases (genetics, metabolism)
• HEK293 Cells
• Histone Deacetylases (genetics, metabolism)
• Humans
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Neoplasm Proteins (genetics, metabolism)
• Neoplasms (enzymology, genetics, pathology)
• Signal Transduction
• p300-CBP Transcription Factors (genetics, metabolism)