Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

Sirtuin

  • Xiaogang Chu
  • Ryan George
  • Raghavan Raju
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101761

Synonyms

Background

The Sir2 family of proteins were first discovered in Saccharomyces cerevisiae. The sirtuins, class III histone deacetylases (HDAC), are NAD+-dependent protein deacetylases and regulate posttranslational acyl modifications in organisms ranging from bacteria to humans (Haigis and Guarente 2006; Nakagawa and Guarente 2011). The seven sirtuin proteins (SIRT1–SIRT7) in mammals have a conserved core NAD+-binding domain and have diverse substrate proteins, intracellular localizations, and cellular functions (Anderson et al. 2014; Nakagawa and Guarente 2011).

Structure

The sirtuin family of proteins shares a conserved catalytic core of approximately 275 amino acids among most organisms. The acetylated peptide and the NAD+ are bound within a cleft that separates a small zinc-binding domain and a large Rossmann-fold domain. Several invariant amino acids are...

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Notes

Acknowledgments

The work was supported (RR) by a grant (R01GM101927) from the National Institutes of Health, Bethesda, MD, USA.

References

  1. Anderson KA, Green MF, Huynh FK, Wagner GR, Hirschey MD. SnapShot: Mammalian Sirtuins. Cell. 2014;159:956–956.e951.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Avalos JL, Boeke JD, Wolberger C. Structural basis for the mechanism and regulation of Sir2 enzymes. Mol Cell. 2004;13:639–48.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Bordone L, Guarente L. Calorie restriction, SIRT1 and metabolism: understanding longevity. Nat Rev Mol Cell Biol. 2005;6:298–305.PubMedPubMedCentralCrossRefGoogle Scholar
  4. Chalkiadaki A, Guarente L. The multifaceted functions of sirtuins in cancer. Nat Rev Cancer. 2015;15:608–24.PubMedPubMedCentralCrossRefGoogle Scholar
  5. Gomes AP, Price NL, Ling AJ, Moslehi JJ, Montgomery MK, Rajman L, White JP, Teodoro JS, Wrann CD, Hubbard BP, Mercken EM, Palmeira CM, de Cabo R, Rolo AP, Turner N, Bell EL, Sinclair DA. Declining NAD(+) induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging. Cell. 2013;155:1624–38.PubMedPubMedCentralCrossRefGoogle Scholar
  6. Guarente L. Sirtuins as potential targets for metabolic syndrome. Nature. 2006;444:868–74.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Guarente L. Sirtuins and calorie restriction. Nat Rev Mol Cell Biol. 2012;13:207.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Haigis MC, Guarente LP. Mammalian sirtuins – emerging roles in physiology, aging, and calorie restriction. Genes Dev. 2006;20:2913–21.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Haigis MC, Mostoslavsky R, Haigis KM, Fahie K, Christodoulou DC, Murphy AJ, Valenzuela DM, Yancopoulos GD, Karow M, Blander G, Wolberger C, Prolla TA, Weindruch R, Alt FW, Guarente L. SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic beta cells. Cell. 2006;126:941–54.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Hall JA, Dominy JE, Lee Y, Puigserver P. The sirtuin family’s role in aging and age-associated pathologies. J Clin Invest. 2013;123:973–9.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Ham PB 3rd, Raju R. Mitochondrial function in hypoxic ischemic injury and influence of aging. Prog Neurobiol. 2016. http://dx.doi.org/10.1016/j.pneurobio.2016.06.006.Google Scholar
  12. Houtkooper RH, Pirinen E, Auwerx J. Sirtuins as regulators of metabolism and healthspan. Nat Rev Mol Cell Biol. 2012;13:225–38.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Kaeberlein M, McVey M, Guarente L. The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms. Genes Dev. 1999;13:2570–80.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Kanfi Y, Naiman S, Amir G, Peshti V, Zinman G, Nahum L, Bar-Joseph Z, Cohen HY. The sirtuin SIRT6 regulates lifespan in male mice. Nature. 2012;483:218–21.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Nakagawa T, Guarente L. Sirtuins at a glance. J Cell Sci. 2011;124:833–8.PubMedPubMedCentralCrossRefGoogle Scholar
  16. Poulose N, Raju R. Sirtuin regulation in aging and injury. Biochim Biophys Acta. 2015;1852:2442–55.PubMedPubMedCentralCrossRefGoogle Scholar
  17. Rahman M, Nirala NK, Singh A, Zhu LJ, Taguchi K, Bamba T, Fukusaki E, Shaw LM, Lambright DG, Acharya JK, Acharya UR. Drosophila Sirt2/mammalian SIRT3 deacetylates ATP synthase beta and regulates complex V activity. J Cell Biol. 2014;206:289–305.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Sebastian C, Satterstrom FK, Haigis MC, Mostoslavsky R. From sirtuin biology to human diseases: an update. J Biol Chem. 2012;287:42444–52.PubMedPubMedCentralCrossRefGoogle Scholar
  19. Shin J, He M, Liu Y, Paredes S, Villanova L, Brown K, Qiu X, Nabavi N, Mohrin M, Wojnoonski K, Li P, Cheng HL, Murphy AJ, Valenzuela DM, Luo H, Kapahi P, Krauss R, Mostoslavsky R, Yancopoulos GD, Alt FW, Chua KF, Chen D. SIRT7 represses Myc activity to suppress ER stress and prevent fatty liver disease. Cell Rep. 2013;5:654–65.PubMedPubMedCentralCrossRefGoogle Scholar
  20. Wang YP, Zhou LS, Zhao YZ, Wang SW, Chen LL, Liu LX, Ling ZQ, Hu FJ, Sun YP, Zhang JY, Yang C, Yang Y, Xiong Y, Guan KL, Ye D. Regulation of G6PD acetylation by SIRT2 and KAT9 modulates NADPH homeostasis and cell survival during oxidative stress. EMBO J. 2014;33:1304–20.PubMedPubMedCentralGoogle Scholar

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© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Augusta UniversityAugustaUSA