SIRT6, a protein with many faces

Biogerontology

Volumn 14, Issue 6, 2013, Pages 629-639

  Gertler, Asaf A ^a   Cohen, Haim Y ^a  

^a BAR ILAN UNIVERSITY   (Israel)

Author keywords

Ageing; Deacylation; SIRT6

Indexed keywords

SIRTUIN 6;

CATALYSIS; CELLULAR DISTRIBUTION; CRYSTAL STRUCTURE; DNA REPAIR; ENZYME ACTIVITY; ENZYME METABOLISM; ENZYME REGULATION; GENOMIC INSTABILITY; HUMAN; INTRACELLULAR SPACE; NEOPLASM; PRIORITY JOURNAL; REVIEW;

ACETYLATION; AGE FACTORS; AGING; ANIMALS; CATALYSIS; DNA REPAIR; GENE EXPRESSION REGULATION, ENZYMOLOGIC; GENOMIC INSTABILITY; HUMANS; NEOPLASMS; PROTEIN CONFORMATION; PROTEIN PROCESSING, POST-TRANSLATIONAL; SIGNAL TRANSDUCTION; SIRTUINS; SUBSTRATE SPECIFICITY;

EID: 84890569395     PISSN: 13895729     EISSN: 15736768     Source Type: Journal    
DOI: 10.1007/s10522-013-9478-8     Document Type: Review

References (94)

1. Adler AS, Sinha S, Kawahara TL, Zhang JY, Segal E, Chang HY (2007) Motif module map reveals enforcement of aging by continual NF-kappaB activity. Genes Dev 21(24):3244-3257. doi: 10.1101/gad.1588507
2. Adler AS, Kawahara TL, Segal E, Chang HY (2008) Reversal of aging by NFkappaB blockade. Cell Cycle 7(5):556-559
3. Ahel D, Horejsí Z, Wiechens N, Polo SE, Garcia-Wilson E, Ahel I, Flynn H, Skehel M, West SC, Jackson SP, Owen-Hughes T, Boulton SJ (2009) Poly(ADP-ribose)-dependent regulation of DNA repair by the chromatin remodeling enzyme ALC1. Science 325(5945):1240-1243. doi: 10.1126/science.1177321
4. Aragonés J, Fraisl P, Baes M, Carmeliet P (2009) Oxygen sensors at the crossroad of metabolism. Cell Metab 9(1):11-22. doi: 10.1016/j.cmet.2008. 10.001
5. Ardestani PM, Liang F (2012) Sub-cellular localization, expression and functions of Sirt6 during the cell cycle in HeLa cells. Nucleus 3(5):442-451. doi: 10.4161/nucl.21134
6. Baar K, Song Z, Semenkovich CF, Jones TE, Han DH, Nolte LA, Ojuka EO, Chen M, Holloszy JO (2003) Skeletal muscle overexpression of nuclear respiratory factor 1 increases glucose transport capacity. FASEB J 17(12):1666-1673. doi: 10.1096/fj.03-0049com
7. Beneke S (2012) Regulation of chromatin structure by poly(ADP-ribosyl) ation. Front Genet 3:169. doi: 10.3389/fgene.2012.00169
8. Biswas M, Chan JY (2010) Role of Nrf1 in antioxidant response element-mediated gene expression and beyond. Toxicol Appl Pharmacol 244(1):16-20. doi: 10.1016/j.taap.2009.07.034
9. Bitterman KJ, Anderson RM, Cohen HY, Latorre-Esteves M, Sinclair DA (2002) Inhibition of silencing and accelerated aging by nicotinamide, a putative negative regulator of yeast sir2 and human SIRT1. J Biol Chem 277(47):45099-45107. doi: 10.1074/jbc.M205670200
10. Cairns RA, Harris IS, Mak TW (2011) Regulation of cancer cell metabolism. Nat Rev Cancer 11(2):85-95. doi: 10.1038/nrc2981
11. Carafa V, Nebbioso A, Altucci L (2013) Sirtuins and Disease: The Road Ahead. Frontiers in Pharmacology 3. doi: 10.3389/fphar.2012.00004
12. Cardus A, Uryga AK, Walters G, Erusalimsky JD (2013) SIRT6 protects human endothelial cells from DNA damage, telomere dysfunction, and senescence. Cardiovasc Res. doi: 10.1093/cvr/cvs352
13. Chakrabarty SP, Balaram H (2010) Reversible binding of zinc in Plasmodium falciparum Sir2: structure and activity of the apoenzyme. Biochim Biophys Acta 1804(9):1743-1750. doi: 10.1016/j.bbapap.2010.06.010
14. Chambers SM, Shaw CA, Gatza C, Fisk CJ, Donehower LA, Goodell MA (2007) Aging hematopoietic stem cells decline in function and exhibit epigenetic dysregulation. PLoS Biol 5(8):e201. doi: 10.1371/journal.pbio.0050201
15. Chen D, Thomas EL, Kapahi P (2009) HIF-1 modulates dietary restriction-mediated lifespan extension via IRE-1 in Caenorhabditis elegans. PLoS Genet 5(5):e1000486. doi: 10.1371/journal.pgen.1000486
16. Das M, Garlick DS, Greiner DL, Davis RJ (2011) The role of JNK in the development of hepatocellular carcinoma. Genes Dev 25(6):634-645. doi: 10.1101/gad.1989311
17. Dávalos A, Goedeke L, Smibert P, Ramírez CM, Warrier NP, Andreo U, Cirera-Salinas D, Rayner K, Suresh U, Pastor-Pareja JC, Esplugues E, Fisher EA, Penalva LO, Moore KJ, Suárez Y, Lai EC, Fernández- Hernando C (2011) miR-33a/b contribute to the regulation of fatty acid metabolism and insulin signaling. Proc Natl Acad Sci USA 108(22):9232-9237. doi: 10.1073/pnas.1102281108
18. Dephoure N, Zhou C, Villén J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP (2008) A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci USA 105(31):10762-10767. doi: 10.1073/pnas.0805139105
19. Dominy JE, Lee Y, Jedrychowski MP, Chim H, Jurczak MJ, Camporez JP, Ruan HB, Feldman J, Pierce K, Mostoslavsky R, Denu JM, Clish CB, Yang X, Shulman GI, Gygi SP, Puigserver P (2012) The deacetylase Sirt6 activates the acetyltransferase GCN5 and suppresses hepatic gluconeogenesis. Mol Cell 48(6):900-913. doi: 10.1016/j.molcel.2012.09.030
20. Eferl R, Ricci R, Kenner L, Zenz R, David JP, Rath M, Wagner EF (2003) Liver tumor development. c-Jun antagonizes the proapoptotic activity of p53. Cell 112(2):181-192
21. Elhanati S, Kanfi Y, Varvak A, Roichman A, Carmel-Gross I, Barth S, Gibor G, Cohen HY (2013) Multiple regulatory layers of SREBP1/2 by SIRT6. Cell Rep 4(5):905-912. doi: 10.1016/j.celrep.2013.08.006
22. El-Khamisy SF, Masutani M, Suzuki H, Caldecott KW (2003) A requirement for PARP-1 for the assembly or stability of XRCC1 nuclear foci at sites of oxidative DNA damage. Nucleic Acids Res 31(19):5526-5533
23. Ferber EC, Peck B, Delpuech O, Bell GP, East P, Schulze A (2012) FOXO3a regulates reactive oxygen metabolism by inhibiting mitochondrial gene expression. Cell Death Differ 19(6):968-979. doi: 10.1038/cdd.2011.179
24. Flachsbart F, Caliebe A, Kleindorp R, Blanché H, von Eller-Eberstein H, Nikolaus S, Schreiber S, Nebel A (2009) Association of FOXO3A variation with human longevity confirmed in German centenarians. Proc Natl Acad Sci USA 106(8):2700-2705. doi: 10.1073/pnas.0809594106
25. Frye RA (2000) Phylogenetic classification of prokaryotic and eukaryotic Sir2-like proteins. Biochem Biophys Res Commun 273(2):793-798. doi: 10.1006/bbrc.2000.3000
26. Gil R, Barth S, Kanfi Y, Cohen HY (2013) SIRT6 exhibits nucleosome-dependent deacetylase activity. Nucleic Acids Res. doi: 10.1093/nar/gkt642
27. Greiss S, Gartner A (2009) Sirtuin/Sir2 phylogeny, evolutionary considerations and structural conservation. Mol Cells 28(5):407-415. doi: 10.1007/s10059-009-0169-x
28. Hassa PO, Haenni SS, Elser M, Hottiger MO (2006) Nuclear ADP-ribosylation reactions in mammalian cells: where are we today and where are we going? Microbiol Mol Biol Rev 70(3):789-829. doi: 10.1128/MMBR.00040-05
29. Hayden MS, Ghosh S (2004) Signaling to NF-kappaB. Genes Dev 18(18):2195-2224. doi: 10.1101/gad.1228704
30. Huertas P (2010) DNA resection in eukaryotes: deciding how to fix the break. Nat Struct Mol Biol 17(1):11-16. doi: 10.1038/nsmb.1710
31. Hui L, Bakiri L, Mairhorfer A, Schweifer N, Haslinger C, Kenner L, Komnenovic V, Scheuch H, Beug H, Wagner EF (2007) p38alpha suppresses normal and cancer cell proliferation by antagonizing the JNK-c-Jun pathway. Nat Genet 39(6):741-749. doi: 10.1038/ng2033
32. Hui L, Zatloukal K, Scheuch H, Stepniak E, Wagner EF (2008) Proliferation of human HCC cells and chemically induced mouse liver cancers requires JNK1-dependent p21 downregulation. J Clin Invest 118(12):3943-3953. doi: 10.1172/JCI37156
33. Jiang H, Khan S, Wang Y, Charron G, He B, Sebastian C, Du J, Kim R, Ge E, Mostoslavsky R, Hang HC, Hao Q, Lin H (2013) SIRT6 regulates TNF-[agr] secretion through hydrolysis of long-chain fatty acyl lysine. Nature 496:110-113. doi: 10.1038/nature12038
34. Kaidi A, Weinert BT, Choudhary C, Jackson SP (2010) Human SIRT6 promotes DNA end resection through CtIP deacetylation. Science 329(5997):1348-1353. doi: 329/5997/1348
35. Kanfi Y, Shalman R, Peshti V, Pilosof SN, Gozlan YM, Pearson KJ, Lerrer B, Moazed D, Marine JC, de Cabo R, Cohen HY (2008) Regulation of SIRT6 protein levels by nutrient availability. FEBS Lett 582(5):543-548. doi: 10.1016/j.febslet.2008.01.019
36. Kanfi Y, Peshti V, Gil R, Naiman S, Nahum L, Levin E, Kronfeld-Schor N, Cohen HY (2010) SIRT6 protects against pathological damage caused by diet-induced obesity. Aging Cell 9(2):162-173. doi: 10.1111/j.1474-9726.2009. 00544.x
37. Kanfi Y, Naiman S, Amir G, Peshti V, Zinman G, Nahum L, Bar-Joseph Z, Cohen HY (2012) The sirtuin SIRT6 regulates lifespan in male mice. Nature 483(7388):218-221. doi: 10.1038/nature10815
38. Karmakar P, Piotrowski J, Brosh RM, Sommers JA, Miller SP, Cheng WH, Snowden CM, Ramsden DA, Bohr VA (2002) Werner protein is a target of DNA-dependent protein kinase in vivo and in vitro, and its catalytic activities are regulated by phosphorylation. J Biol Chem 277(21):18291-18302. doi: 10.1074/jbc.M111523200
39. Kawahara TL, Michishita E, Adler AS, Damian M, Berber E, Lin M, McCord RA, Ongaigui KC, Boxer LD, Chang HY, Chua KF (2009) SIRT6 links histone H3 lysine 9 deacetylation to NF-kappaB-dependent gene expression and organismal life span. Cell 136(1):62-74. doi: 10.1016/j.cell.2008.10.052
40. Kawahara TL, Rapicavoli NA, Wu AR, Qu K, Quake SR, Chang HY (2011) Dynamic chromatin localization of Sirt6 shapes stress- and aging-related transcriptional networks. PLoS Genet 7(6):e1002153. doi: 10.1371/journal.pgen. 1002153
41. Kelly DP, Scarpulla RC (2004) Transcriptional regulatory circuits controlling mitochondrial biogenesis and function. Genes Dev 18(4):357-368. doi: 10.1101/gad.1177604
42. Khongkow M, Olmos Y, Gong C, Gomes AR, Monteiro LJ, Yagüe E, Cavaco TB, Khongkow P, Man EP, Laohasinnarong S, Koo CY, Harada-Shoji N, Tsang JW, Coombes RC, Schwer B, Khoo US, Lam EW (2013) SIRT6 modulates paclitaxel and epirubicin resistance and survival in breast cancer. Carcinogenesis 34(7):1476-1486. doi: 10.1093/carcin/bgt098
43. Kim HS, Xiao C, Wang RH, Lahusen T, Xu X, Vassilopoulos A, Vazquez-Ortiz G, Jeong WI, Park O, Ki SH, Gao B, Deng CX (2010) Hepatic-specific disruption of SIRT6 in mice results in fatty liver formation due to enhanced glycolysis and triglyceride synthesis. Cell Metab 12(3):224-236. doi: 10.1016/j.cmet.2010.06. 009
44. Kinzler KW, Vogelstein B (1996) Lessons from hereditary colorectal cancer. Cell 87(2):159-170
45. Lai CC, Lin PM, Lin SF, Hsu CH, Lin HC, Hu ML, Hsu CM, Yang MY (2013) Altered expression of SIRT gene family in head and neck squamous cell carcinoma. Tumour Biol. doi: 10.1007/s13277-013-0726-y
46. Lau C, Niere M, Ziegler M (2009) The NMN/NaMN adenylyltransferase (NMNAT) protein family. Front Biosci 14:410-431
47. Lerrer B, Cohen HY (2013) The guardian: metabolic and tumour-suppressive effects of SIRT6. EMBO J 32(1):7-8. doi: 10.1038/emboj.2012.332
48. Lin SJ, Defossez PA, Guarente L (2000) Requirement of NAD and SIR2 for life-span extension by calorie restriction in Saccharomyces cerevisiae. Science 289(5487):2126-2128
49. Liszt G, Ford E, Kurtev M, Guarente L (2005) Mouse Sir2 homolog SIRT6 is a nuclear ADP-ribosyltransferase. J Biol Chem 280(22):21313-21320. doi: 10.1074/jbc.M413296200
50. Liu Y, Xie QR, Wang B, Shao J, Zhang T, Liu T, Huang G, Xia W (2013) Inhibition of SIRT6 in prostate cancer reduces cell viability and increases sensitivity to chemotherapeutics. Protein Cell. doi: 10.1007/s13238-013-3054-5
51. Lum JJ, Bui T, Gruber M, Gordan JD, DeBerardinis RJ, Covello KL, Simon MC, Thompson CB (2007) The transcription factor HIF-1alpha plays a critical role in the growth factor-dependent regulation of both aerobic and anaerobic glycolysis. Genes Dev 21(9):1037-1049. doi: 10.1101/gad.1529107
52. Ma W, Stafford LJ, Li D, Luo J, Li X, Ning G, Liu M (2007) GCIP/CCNDBP1, a helix-loop-helix protein, suppresses tumorigenesis. J Cell Biochem 100(6):1376-1386. doi: 10.1002/jcb.21140
53. Mahlknecht U, Ho AD, Voelter-Mahlknecht S (2006) Chromosomal organization and fluorescence in situ hybridization of the human Sirtuin 6 gene. Int J Oncol 28(2):447-456
54. Mao Z, Hine C, Tian X, Van Meter M, Au M, Vaidya A, Seluanov A, Gorbunova V (2011) SIRT6 promotes DNA repair under stress by activating PARP1. Science 332(6036):1443-1446. doi: 10.1126/science.1202723
55. Mao Z, Tian X, Van Meter M, Ke Z, Gorbunova V, Seluanov A (2012) Sirtuin 6 (SIRT6) rescues the decline of homologous recombination repair during replicative senescence. Proc Natl Acad Sci USA 109(29):11800-11805. doi: 10.1073/pnas.1200583109
56. Marquardt JU, Fischer K, Baus K, Kashyap A, Ma S, Krupp M, Linke M, Teufel A, Zechner U, Strand D, Thorgeirsson SS, Galle PR, Strand S (2013) SIRT6 dependent genetic and epigenetic alterations are associated with poor clinical outcome in HCC patients. Hepatology. doi: 10.1002/hep.26413
57. McCay CM, Crowell MF, Maynard LA (1989) The effect of retarded growth upon the length of life span and upon the ultimate body size. 1935. Nutrition 5(3):155-171 discussion 172
58. McCord RA, Michishita E, Hong T, Berber E, Boxer LD, Kusumoto R, Guan S, Shi X, Gozani O, Burlingame AL, Bohr VA, Chua KF (2009) SIRT6 stabilizes DNA-dependent protein kinase at chromatin for DNA double-strand break repair. Aging (Albany NY) 1(1):109-121
59. Mehta R, Steinkraus KA, Sutphin GL, Ramos FJ, Shamieh LS, Huh A, Davis C, Chandler-Brown D, Kaeberlein M (2009) Proteasomal regulation of the hypoxic response modulates aging in C. elegans. Science 324(5931):1196-1198. doi: 10.1126/science.1173507
60. Michishita E, Park JY, Burneskis JM, Barrett JC, Horikawa I (2005) Evolutionarily conserved and nonconserved cellular localizations and functions of human SIRT proteins. Mol Biol Cell 16(10):4623-4635. doi: 10.1091/mbc.E05-01-0033
61. Michishita E, McCord RA, Berber E, Kioi M, Padilla-Nash H, Damian M, Cheung P, Kusumoto R, Kawahara TL, Barrett JC, Chang HY, Bohr VA, Ried T, Gozani O, Chua KF (2008) SIRT6 is a histone H3 lysine 9 deacetylase that modulates telomeric chromatin. Nature 452(7186):492-496. doi: 10.1038/nature06736
62. Michishita E, McCord RA, Boxer LD, Barber MF, Hong T, Gozani O, Chua KF (2009) Cell cycle-dependent deacetylation of telomeric histone H3 lysine K56 by human SIRT6. Cell Cycle 8(16):2664-2666
63. Mimitou EP, Symington LS (2009) DNA end resection: many nucleases make light work. DNA Repair (Amst) 8(9):983-995. doi: 10.1016/j.dnarep.2009.04.017
64. Min J, Landry J, Sternglanz R, Xu RM (2001) Crystal structure of a SIR2 homolog-NAD complex. Cell 105(2):269-279
65. Min L, Ji Y, Bakiri L, Qiu Z, Cen J, Chen X, Chen L, Scheuch H, Zheng H, Qin L, Zatloukal K, Hui L, Wagner EF (2012) Liver cancer initiation is controlled by AP-1 through SIRT6-dependent inhibition of survivin. Nat Cell Biol 14(11):1203-1211. doi: 10.1038/ncb2590
66. Mostoslavsky R, Chua KF, Lombard DB, Pang WW, Fischer MR, Gellon L, Liu P, Mostoslavsky G, Franco S, Murphy MM, Mills KD, Patel P, Hsu JT, Hong AL, Ford E, Cheng HL, Kennedy C, Nunez N, Bronson R, Frendewey D, Auerbach W, Valenzuela D, Karow M, Hottiger MO, Hursting S, Barrett JC, Guarente L, Mulligan R, Demple B, Yancopoulos GD, Alt FW (2006) Genomic instability and aging-like phenotype in the absence of mammalian SIRT6. Cell 124(2):315-329. doi: 10.1016/j.cell.2005.11.044
67. Naiman S, Cohen HY (2012) The contentious history of sirtuin debates. Rambam Maimonides Med J 3(4):e0022. doi: 10.5041/RMMJ.10093
68. Naiman S, Kanfi Y, Cohen HY (2012) Sirtuins as regulators of mammalian aging. Aging (Albany NY) 4(8):521-522
69. Nemoto S, Fergusson MM, Finkel T (2004) Nutrient availability regulates SIRT1 through a forkhead-dependent pathway. Science 306(5704):2105-2108. doi: 10.1126/science.1101731
70. Pan PW, Feldman JL, Devries MK, Dong A, Edwards AM, Denu JM (2011) Structure and biochemical functions of SIRT6. J Biol Chem 286(16):14575-14587. doi: 10.1074/jbc.M111.218990
71. Qi W, Fitchev PS, Cornwell ML, Greenberg J, Cabe M, Weber CR, Roy HK, Crawford SE, Savkovic SD (2013) FOXO3 growth inhibition of colonic cells is dependent on intraepithelial lipid droplet density. J Biol Chem. doi: 10.1074/jbc.M113.470617
72. Rongvaux A, Andris F, Van Gool F, Leo O (2003) Reconstructing eukaryotic NAD metabolism. BioEssays 25(7):683-690. doi: 10.1002/bies.10297
73. Sanders BD, Jackson B, Marmorstein R (2010) Structural basis for sirtuin function: what we know and what we don't. Biochim Biophys Acta 1804(8):1604-1616. doi: 10.1016/j.bbapap.2009.09.009
74. Sansom OJ, Meniel VS, Muncan V, Phesse TJ, Wilkins JA, Reed KR, Vass JK, Athineos D, Clevers H, Clarke AR (2007) Myc deletion rescues Apc deficiency in the small intestine. Nature 446(7136):676-679. doi: 10.1038/nature05674
75. Sartori AA, Lukas C, Coates J, Mistrik M, Fu S, Bartek J, Baer R, Lukas J, Jackson SP (2007) Human CtIP promotes DNA end resection. Nature 450(7169):509-514. doi: 10.1038/nature06337
76. Sauve AA, Schramm VL (2003) Sir2 regulation by nicotinamide results from switching between base exchange and deacetylation chemistry. Biochemistry 42(31):9249-9256. doi: 10.1021/bi034959l
77. Schuetz A, Min J, Antoshenko T, Wang CL, Allali-Hassani A, Dong A, Loppnau P, Vedadi M, Bochkarev A, Sternglanz R, Plotnikov AN (2007) Structural basis of inhibition of the human NAD + -dependent deacetylase SIRT5 by suramin. Structure 15(3):377-389. doi: 10.1016/j.str.2007.02.002
78. Schwer B, Schumacher B, Lombard DB, Xiao C, Kurtev MV, Gao J, Schneider JI, Chai H, Bronson RT, Tsai LH, Deng CX, Alt FW (2010) Neural sirtuin 6 (Sirt6) ablation attenuates somatic growth and causes obesity. Proc Natl Acad Sci USA 107(50):21790-21794. doi: 10.1073/pnas.1016306107
79. Seagroves TN, Ryan HE, Lu H, Wouters BG, Knapp M, Thibault P, Laderoute K, Johnson RS (2001) Transcription factor HIF-1 is a necessary mediator of the pasteur effect in mammalian cells. Mol Cell Biol 21(10):3436-3444. doi: 10.1128/MCB.21.10.3436-3444.2001
80. Sebastián C, Zwaans BM, Silberman DM, Gymrek M, Goren A, Zhong L, Ram O, Truelove J, Guimaraes AR, Toiber D, Cosentino C, Greenson JK, Macdonald AI, McGlynn L, Maxwell F, Edwards J, Giacosa S, Guccione E, Weissleder R, Bernstein BE, Regev A, Shiels PG, Lombard DB, Mostoslavsky R (2012) The histone deacetylase SIRT6 is a tumor suppressor that controls cancer metabolism. Cell 151(6):1185-1199. doi: 10.1016/j.cell.2012.10.047
81. Sundaresan NR, Vasudevan P, Zhong L, Kim G, Samant S, Parekh V, Pillai VB, Ravindra PV, Gupta M, Jeevanandam V, Cunningham JM, Deng CX, Lombard DB, Mostoslavsky R, Gupta MP (2012) The sirtuin SIRT6 blocks IGF-Akt signaling and development of cardiac hypertrophy by targeting c-Jun. Nat Med 18(11):1643-1650. doi: 10.1038/nm.2961
82. Tennen RI, Berber E, Chua KF (2010) Functional dissection of SIRT6: identification of domains that regulate histone deacetylase activity and chromatin localization. Mech Ageing Dev 131(3):185-192. doi: 10.1016/j.mad.2010.01.006
83. Tennen RI, Bua DJ, Wright WE, Chua KF (2011) SIRT6 is required for maintenance of telomere position effect in human cells. Nat Commun 2:433. doi: 10.1038/ncomms1443
84. Toiber D, Erdel F, Bouazoune K, Silberman DM, Zhong L, Mulligan P, Sebastian C, Cosentino C, Martinez-Pastor B, Giacosa S, D'Urso A, Näär AM, Kingston R, Rippe K, Mostoslavsky R (2013) SIRT6 recruits SNF2H to DNA break sites, preventing genomic instability through chromatin remodeling. Mol Cell 51(4):454-468. doi: 10.1016/j.molcel.2013.06.018
85. Tong L, Denu JM (2010) Function and metabolism of sirtuin metabolite O-acetyl-ADP-ribose. Biochim Biophys Acta 1804(8):1617-1625. doi: 10.1016/j.bbapap.2010.02.007
86. Ullsperger M, von Cramon DY (2003) Error monitoring using external feedback: specific roles of the habenular complex, the reward system, and the cingulate motor area revealed by functional magnetic resonance imaging. J Neurosci 23(10):4308-4314
87. Van Meter M, Mao Z, Gorbunova V, Seluanov A (2011) SIRT6 overexpression induces massive apoptosis in cancer cells but not in normal cells. Cell Cycle 10(18):3153-3158
88. Vander Heiden MG, Cantley LC, Thompson CB (2009) Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 324(5930):1029-1033. doi: 10.1126/science.1160809
89. Willcox BJ, Donlon TA, He Q, Chen R, Grove JS, Yano K, Masaki KH, Willcox DC, Rodriguez B, Curb JD (2008) FOXO3A genotype is strongly associated with human longevity. Proc Natl Acad Sci USA 105(37):13987-13992. doi: 10.1073/pnas.0801030105
90. Xiao C, Kim HS, Lahusen T, Wang RH, Xu X, Gavrilova O, Jou W, Gius D, Deng CX (2010) SIRT6 deficiency results in severe hypoglycemia by enhancing both basal and insulin-stimulated glucose uptake in mice. J Biol Chem. doi: 10.1074/jbc.M110.168039
91. Yang B, Zwaans BM, Eckersdorff M, Lombard DB (2009) The sirtuin SIRT6 deacetylates H3 K56Ac in vivo to promote genomic stability. Cell Cycle 8(16):2662-2663
92. Yuan J, Pu M, Zhang Z, Lou Z (2009) Histone H3-K56 acetylation is important for genomic stability in mammals. Cell Cycle 8(11):1747-1753
93. Zhang T, Berrocal JG, Frizzell KM, Gamble MJ, DuMond ME, Krishnakumar R, Yang T, Sauve AA, Kraus WL (2009) Enzymes in the NAD + salvage pathway regulate SIRT1 activity at target gene promoters. J Biol Chem 284(30):20408-20417. doi: 10.1074/jbc.M109.016469
94. Zhong L, D'Urso A, Toiber D, Sebastian C, Henry RE, Vadysirisack DD, Guimaraes A, Marinelli B, Wikstrom JD, Nir T, Clish CB, Vaitheesvaran B, Iliopoulos O, Kurland I, Dor Y, Weissleder R, Shirihai OS, Ellisen LW, Espinosa JM, Mostoslavsky R (2010) The histone deacetylase Sirt6 regulates glucose homeostasis via Hif1alpha. Cell 140(2):280-293. doi: S0092-8674(09)01627-4