KAT(ching) Metabolism by the Tail: Insight into the Links Between Lysine Acetyltransferases and Metabolism

Overview

Journal Chembiochem

Specialty Biochemistry

Date 2011 Jan 19

PMID 21243716

Citations 71

Authors

Brittany N Albaugh

Kevin M Arnold

John M Denu

Affiliations

Soon will be listed here.

Abstract

Post-translational modifications of histones elicit structural and functional changes within chromatin that regulate various epigenetic processes. Epigenetic mechanisms rely on enzymes whose activities are driven by coenzymes and metabolites from intermediary metabolism. Lysine acetyltransferases (KATs) catalyze the transfer of acetyl groups from acetyl-CoA to epsilon amino groups. Utilization of this critical metabolite suggests these enzymes are modulated by the metabolic status of the cell. This review highlights studies linking KATs to metabolism. We cover newly identified acyl modifications (propionylation and butyrylation), discuss the control of KAT activity by cellular acetyl-CoA levels, and provide insights into how acetylation regulates metabolic proteins. We conclude with a discussion of the current approaches to identifying novel KATs and their metabolic substrates.

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References

Starai V, Takahashi H, Boeke J, Escalante-Semerena J . Short-chain fatty acid activation by acyl-coenzyme A synthetases requires SIR2 protein function in Salmonella enterica and Saccharomyces cerevisiae. Genetics. 2003; 163(2):545-55. PMC: 1462443. DOI: 10.1093/genetics/163.2.545. View

Lin Y, Lu J, Zhang J, Walter W, Dang W, Wan J . Protein acetylation microarray reveals that NuA4 controls key metabolic target regulating gluconeogenesis. Cell. 2009; 136(6):1073-84. PMC: 2696288. DOI: 10.1016/j.cell.2009.01.033. View

Musselman C, Mansfield R, Garske A, Davrazou F, Kwan A, Oliver S . Binding of the CHD4 PHD2 finger to histone H3 is modulated by covalent modifications. Biochem J. 2009; 423(2):179-87. PMC: 2885444. DOI: 10.1042/BJ20090870. View

Duncan M, Robinson M, DellOrco R . Kinetics of histone hyperacetylation and deacetylation in human diploid fibroblasts. Biochim Biophys Acta. 1983; 762(2):221-6. DOI: 10.1016/0167-4889(83)90074-5. View

Starai V, Celic I, Cole R, Boeke J, Escalante-Semerena J . Sir2-dependent activation of acetyl-CoA synthetase by deacetylation of active lysine. Science. 2002; 298(5602):2390-2. DOI: 10.1126/science.1077650. View

Wente S, Rout M . The nuclear pore complex and nuclear transport. Cold Spring Harb Perspect Biol. 2010; 2(10):a000562. PMC: 2944363. DOI: 10.1101/cshperspect.a000562. View

Hallows W, Lee S, Denu J . Sirtuins deacetylate and activate mammalian acetyl-CoA synthetases. Proc Natl Acad Sci U S A. 2006; 103(27):10230-10235. PMC: 1480596. DOI: 10.1073/pnas.0604392103. View

Berndsen C, Albaugh B, Tan S, Denu J . Catalytic mechanism of a MYST family histone acetyltransferase. Biochemistry. 2007; 46(3):623-9. PMC: 2752042. DOI: 10.1021/bi602513x. View

Imai S, Guarente L . Ten years of NAD-dependent SIR2 family deacetylases: implications for metabolic diseases. Trends Pharmacol Sci. 2010; 31(5):212-20. PMC: 3526941. DOI: 10.1016/j.tips.2010.02.003. View

10.

Hosokawa Y, Shimomura Y, Harris R, Ozawa T . Determination of short-chain acyl-coenzyme A esters by high-performance liquid chromatography. Anal Biochem. 1986; 153(1):45-9. DOI: 10.1016/0003-2697(86)90058-8. View

11.

Nakahata Y, Kaluzova M, Grimaldi B, Sahar S, Hirayama J, Chen D . The NAD+-dependent deacetylase SIRT1 modulates CLOCK-mediated chromatin remodeling and circadian control. Cell. 2008; 134(2):329-40. PMC: 3526943. DOI: 10.1016/j.cell.2008.07.002. View

12.

Smith B, Denu J . Acetyl-lysine analog peptides as mechanistic probes of protein deacetylases. J Biol Chem. 2007; 282(51):37256-65. DOI: 10.1074/jbc.M707878200. View

13.

Yang Y, Ascano J, Hang H . Bioorthogonal chemical reporters for monitoring protein acetylation. J Am Chem Soc. 2010; 132(11):3640-1. PMC: 2848987. DOI: 10.1021/ja908871t. View

14.

Grunstein M . Histone acetylation in chromatin structure and transcription. Nature. 1997; 389(6649):349-52. DOI: 10.1038/38664. View

15.

Starai V, Escalante-Semerena J . Identification of the protein acetyltransferase (Pat) enzyme that acetylates acetyl-CoA synthetase in Salmonella enterica. J Mol Biol. 2004; 340(5):1005-12. DOI: 10.1016/j.jmb.2004.05.010. View

16.

Struhl K . Histone acetylation and transcriptional regulatory mechanisms. Genes Dev. 1998; 12(5):599-606. DOI: 10.1101/gad.12.5.599. View

17.

Durrin L, MANN R, Kayne P, Grunstein M . Yeast histone H4 N-terminal sequence is required for promoter activation in vivo. Cell. 1991; 65(6):1023-31. DOI: 10.1016/0092-8674(91)90554-c. View

18.

Dashwood R, Ho E . Dietary histone deacetylase inhibitors: from cells to mice to man. Semin Cancer Biol. 2007; 17(5):363-9. PMC: 2737738. DOI: 10.1016/j.semcancer.2007.04.001. View

19.

Saha R, Pahan K . HATs and HDACs in neurodegeneration: a tale of disconcerted acetylation homeostasis. Cell Death Differ. 2005; 13(4):539-50. PMC: 1963416. DOI: 10.1038/sj.cdd.4401769. View

20.

Scholte H, Groot P . Organ and intracellular localization of short-chain acyl-CoA synthetases in rat and guinea-pig. Biochim Biophys Acta. 1975; 409(3):283-96. DOI: 10.1016/0005-2760(75)90024-7. View