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Cancer Metab. 2015 Sep 23;3:10. doi: 10.1186/s40170-015-0135-3. eCollection 2015.

The rate of glycolysis quantitatively mediates specific histone acetylation sites.

Author information

1
Graduate Field of Biochemistry, Molecular Cell Biology, Cornell University, Ithaca, NY USA ; King Abdullah International Medical Research Center (KAIMRC), Riyadh, Saudi Arabia.
2
Ben May Department of Cancer Research, The University of Chicago, Chicago, IL USA.
3
King Abdullah International Medical Research Center (KAIMRC), Riyadh, Saudi Arabia.
4
Division of Nutritional Sciences, Cornell University, Ithaca, NY USA.
5
Graduate Field of Biochemistry, Molecular Cell Biology, Cornell University, Ithaca, NY USA ; Division of Nutritional Sciences, Cornell University, Ithaca, NY USA ; Department of Pharmacology and Cancer Biology, Duke University Medical School, Durham, NC USA ; Duke Cancer Institute, Duke University Medical School, Durham, NC USA ; Duke Molecular Physiology Institute, Duke University Medical School, Durham, NC USA.

Abstract

BACKGROUND:

Glucose metabolism links metabolic status to protein acetylation. However, it remains poorly understood to what extent do features of glucose metabolism contribute to protein acetylation and whether the process can be dynamically and quantitatively regulated by differing rates of glycolysis.

RESULTS:

Here, we show that titratable rates of glycolysis with corresponding changes in the levels of glycolytic intermediates result in a graded remodeling of a bulk of the metabolome and resulted in gradual changes in total histone acetylation levels. Dynamic histone acetylation levels were found and most strongly correlated with acetyl coenzyme A (ac-CoA) levels and inversely associated with the ratio of ac-CoA to free CoA. A multiplexed stable isotopic labeling by amino acids in cell culture (SILAC)-based proteomics approach revealed that the levels of half of identified histone acetylation sites as well as other lysine acylation modifications are tuned by the rate of glycolysis demonstrating that glycolytic rate affects specific acylation sites.

CONCLUSIONS:

We demonstrate that histone acylation is directly sensed by glucose flux in a titratable, dose-dependent manner that is modulated by glycolytic flux and that a possible function of the Warburg Effect, a metabolic state observed in cancers with enhanced glucose metabolism, is to confer specific signaling effects on cells.

KEYWORDS:

Acetyl coenzyme A (acetyl-CoA); Cancer; Glycolysis; Histone acetylation; Warburg effect

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