Sirtuin 1 (SIRT1): The misunderstood HDAC

Journal of Biomolecular Screening

Volumn 16, Issue 10, 2011, Pages 1153-1169

  Stünkel, Walter ^a   Campbell, Robert M ^b  

^a AGENCY FOR SCIENCE   (Singapore)

^b ELI LILLY AND COMPANY   (United States)

Author keywords

cancer and cancer drugs; CNS and PNS diseases; epigenetics; immune system diseases; metabolic diseases

Indexed keywords

ALPHA TUBULIN; BUTEIN; HISTONE DEACETYLASE 1; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; MYRICETIN; PICEATANNOL; PROTEIN BAX; PROTEIN BCL 2; PROTEIN P53; QUERCETIN; RESVERATROL; SIRTUIN 1; SIRTUIN 2; SIRTUIN 3; SIRTUIN 4; SIRTUIN 5; SIRTUIN 6; SIRTUIN 7; TRANSFORMING GROWTH FACTOR BETA;

ALZHEIMER DISEASE; CANCER CELL CULTURE; CD4+ T LYMPHOCYTE; CHRONIC OBSTRUCTIVE LUNG DISEASE; DIABETES MELLITUS; DNA DAMAGE; ENZYMATIC ASSAY; EPITHELIAL MESENCHYMAL TRANSITION; EXCISION REPAIR; GENE SILENCING; GENE TARGETING; GLUCONEOGENESIS; HUMAN; IMMUNE SYSTEM; IN VITRO STUDY; IN VIVO STUDY; INSULIN RELEASE; INSULIN SENSITIVITY; NEOPLASM; NERVE DEGENERATION; NONHUMAN; ONCOGENE; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; REVIEW; TUMOR SUPPRESSOR GENE;

ANIMALS; ENZYME ACTIVATION; ENZYME ACTIVATORS; HISTONE DEACETYLASE INHIBITORS; HUMANS; IMMUNE SYSTEM; NEOPLASMS; NEURODEGENERATIVE DISEASES; SIRTUIN 1;

EID: 83455218662     PISSN: 10870571     EISSN: 1552454X     Source Type: Journal    
DOI: 10.1177/1087057111422103     Document Type: Review

References (209)

1. Horio Y., Hayashi T., Kuno A., Kunimoto R.. Cellular and Molecular Effects of Sirtuins in Health and Disease. Clin. Sci. (Lond). 2011 ; 121 (5). 191-203
2. Cen Y., Youn D. Y., Sauve A. A.. Advances in Characterization of Human Sirtuin Isoforms: Chemistries, Targets and Therapeutic Applications. Curr. Med. Chem. 2011 ; 18 (13). 1919-1935
3. Haigis M. C., Sinclair D. A.. Mammalian Sirtuins: Biological Insights and Disease Relevance. Annu. Rev. Pathol. 2010 ; 5: 253-295
4. Michishita E., Park J. Y., Burneskis J. M., Barrett J. C., Horikawa I.. Evolutionarily Conserved and Nonconserved Cellular Localizations and Functions of Human SIRT Proteins. Mol. Biol. Cell. 2005 ; 16 (10). 4623-4635 (Pubitemid 41416446)
5. North B. J., Verdin E.. Interphase Nucleo-Cytoplasmic Shuttling and Localization of SIRT2 during Mitosis. PLoS One. 2007 ; 2 (8). e784
6. Tanno M., Sakamoto J., Miura T., Shimamoto K., Horio Y.. Nucleocytoplasmic Shuttling of the NAD+-Dependent Histone Deacetylase SIRT1. J. Biol. Chem. 2007 ; 282 (9). 6823-6832 (Pubitemid 47100909)
7. Tanner K. G., Landry J., Sternglanz R., Denu J. M.. Silent Information Regulator 2 Family of NAD-Dependent Histone/Protein Deacetylases Generates a Unique Product, 1-O-Acetyl-ADP-Ribose. Proc. Natl. Acad. Sci. U. S. A. 2000 ; 97 (26). 14178-14182 (Pubitemid 32016550)
8. Borra M. T., Langer M. R., Slama J. T., Denu J. M.. Substrate Specificity and Kinetic Mechanism of the Sir2 Family of NAD+-Dependent Histone/Protein Deacetylases. Biochemistry. 2004 ; 43 (30). 9877-9887 (Pubitemid 38993837)
9. Mahlknecht U., Voelter-Mahlknecht S.. Fluorescence In Situ Hybridization and Chromosomal Organization of the Sirtuin 4 Gene (Sirt4) in the Mouse. Biochem. Biophys. Res. Commun. 2009 ; 382 (4). 685-690
10. J. Biol. Chem. Pan P. W. Feldman J. L. Devries M. K. Dong A. Edwards A. M. Denu J. M., ed. 2011: 14575-14587.
11. Liu B., Lin Y., Darwanto A., Song X., Xu G., Zhang K.. Identification and Characterization of Propionylation at Histone H3 Lysine 23 in Mammalian Cells. J. Biol. Chem. 2009 ; 284 (47). 32288-32295
12. 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 (19). 2570-2580 (Pubitemid 29489648)
13. Shore D., Squire M., Nasmyth K. A.. Characterization of Two Genes Required for the Position-Effect Control of Yeast Mating-Type Genes. EMBO J. 1984 ; 3 (12). 2817-2823
14. Saunders L. R., Verdin E.. Sirtuins: Critical Regulators at the Crossroads between Cancer and Aging. Oncogene. 2007 ; 26 (37). 5489-5504 (Pubitemid 47255930)
15. Imai S., Armstrong C. M., Kaeberlein M., Guarente L.. Transcriptional Silencing and Longevity Protein Sir2 Is an NAD-Dependent Histone Deacetylase. Nature. 2000 ; 403 (6771). 795-800 (Pubitemid 30111843)
16. Vaquero A., Scher M., Lee D., Erdjument-Bromage H., Tempst P., Reinberg D.. Human SirT1 Interacts with Histone H1 and Promotes Formation of Facultative Heterochromatin. Mol. Cell. 2004 ; 16 (1). 93-105 (Pubitemid 39330155)
17. Wang R. H., Sengupta K., Li C., Kim H. S., Cao L., Xiao C., Kim S., Xu X., Zheng Y., Chilton B., et al. Impaired DNA Damage Response, Genome Instability, and Tumorigenesis in SIRT1 Mutant Mice. Cancer Cell. 2008 ; 14 (4). 312-323
18. Fraga M. F., Ballestar E., Villar-Garea A., Boix-Chornet M., Espada J., Schotta G., Bonaldi T., Haydon C., Ropero S., Petrie K., et al. Loss of Acetylation at Lys16 and Trimethylation at Lys20 of Histone H4 Is a Common Hallmark of Human Cancer. Nat. Genet. 2005 ; 37 (4). 391-400
19. Dang W., Steffen K. K., Perry R., Dorsey J. A., Johnson F. B., Shilatifard A., Kaeberlein M., Kennedy B. K., Berger S. L.. Histone H4 Lysine 16 Acetylation Regulates Cellular Lifespan. Nature. 2009 ; 459 (7248). 802-807
20. Vempati R. K., Jayani R. S., Notani D., Sengupta A., Galande S., Haldar D.. p300-Mediated Acetylation of Histone H3 Lysine 56 Functions in DNA Damage Response in Mammals. J. Biol. Chem. 2010 ; 285 (37). 28553-28564
21. Kong S., Kim S. J., Sandal B., Lee S. M., Gao B., Zhang D. D., Fang D.. The Type III Histone Deacetylase Sirt1 Suppresses p300-Mediated Histone H3 Lysine 56 Acetylation at Bclaf1 Promoter to Inhibit T Cell Activation. J. Biol. Chem. 2011 ; 286 (19). 16967-16975
22. Zhang J., Lee S. M., Shannon S., Gao B., Chen W., Chen A., Divekar R., McBurney M. W., Braley-Mullen H., Zaghouani H., et al. The Type III Histone Deacetylase Sirt1 Is Essential for Maintenance of T Cell Tolerance in Mice. J. Clin. Invest. 2009 ; 119 (10). 3048-3058
23. Sequeira J., Boily G., Bazinet S., Saliba S., He X., Jardine K., Kennedy C., Staines W., Rousseaux C., Mueller R., et al. Sirt1-null Mice Develop an Autoimmune-Like Condition. Exp. Cell. Res. 2008 ; 314 (16). 3069-3074
24. Vaziri H., Dessain S. K., Ng Eaton E., Imai S. I., Frye R. A., Pandita T. K., Guarente L., Weinberg R. A.. hSIR2(SIRT1) Functions as an NAD-Dependent p53 Deacetylase. Cell. 2001 ; 107 (2). 149-159 (Pubitemid 33035942)
25. Luo J., Nikolaev A. Y., Imai S., Chen D., Su F., Shiloh A., Guarente L., Gu W.. Negative Control of p53 by Sir2alpha Promotes Cell Survival under Stress. Cell. 2001 ; 107 (2). 137-148 (Pubitemid 33035941)
26. Dai J. M., Wang Z. Y., Sun D. C., Lin R. X., Wang S. Q.. SIRT1 Interacts with p73 and Suppresses p73-Dependent Transcriptional Activity. J. Cell. Physiol. 2007 ; 210 (1). 161-166
27. Brunet A., Sweeney L. B., Sturgill J. F., Chua K. F., Greer P. L., Lin Y., Tran H., Ross S. E., Mostoslavsky R., Cohen H. Y., et al. Stress-Dependent Regulation of FOXO Transcription Factors by the SIRT1 Deacetylase. Science. 2004 ; 303 (5666). 2011-2015 (Pubitemid 38393275)
28. Motta M. C., Divecha N., Lemieux M., Kamel C., Chen D., Gu W., Bultsma Y., McBurney M., Guarente L.. Mammalian SIRT1 Represses Forkhead Transcription Factors. Cell. 2004 ; 116 (4). 551-563 (Pubitemid 38264432)
29. van der Horst A., Tertoolen L. G., de Vries-Smits L. M., Frye R. A., Medema R. H., Burgering B. M.. FOXO4 Is Acetylated upon Peroxide Stress and Deacetylated by the Longevity Protein hSir2(SIRT1). J. Biol. Chem. 2004 ; 279 (28). 28873-28879 (Pubitemid 38915754)
30. Xiong S., Salazar G., Patrushev N., Alexander R. W.. FoxO1 Mediates an Autofeedback Loop Regulating SIRT1 Expression. J. Biol. Chem. 2011 ; 286 (7). 5289-5299
31. Ikenoue T., Inoki K., Zhao B., Guan K. L.. PTEN Acetylation Modulates Its Interaction with PDZ Domain. Cancer Res. 2008 ; 68 (17). 6908-6912
32. Guarani V., Deflorian G., Franco C. A., Kruger M., Phng L. K., Bentley K., Toussaint L., Dequiedt F., Mostoslavsky R., Schmidt M. H., et al. Acetylation-Dependent Regulation of Endothelial Notch Signalling by the SIRT1 Deacetylase. Nature. 2011 ; 473 (7346). 234-238
33. Zhao X., Sternsdorf T., Bolger T. A., Evans R. M., Yao T. P.. Regulation of MEF2 by Histone Deacetylase 4- and SIRT1 Deacetylase-Mediated Lysine Modifications. Mol. Cell. Biol. 2005 ; 25 (19). 8456-8464 (Pubitemid 41369167)
34. Dioum E. M., Chen R., Alexander M. S., Zhang Q., Hogg R. T., Gerard R. D., Garcia J. A.. Regulation of Hypoxia-Inducible Factor 2alpha Signaling by the Stress-Responsive Deacetylase Sirtuin 1. Science. 2009 ; 324 (5932). 1289-1293
35. Lim J. H., Lee Y. M., Chun Y. S., Chen J., Kim J. E., Park J. W.. Sirtuin 1 Modulates Cellular Responses to Hypoxia by Deacetylating Hypoxia-Inducible Factor 1alpha. Mol. Cell. 2010 ; 38 (6). 864-878
36. Leiser S. F., Kaeberlein M.. A Role for SIRT1 in the Hypoxic Response. Mol. Cell. 2010 ; 38 (6). 779-780
37. Muth V., Nadaud S., Grummt I., Voit R.. Acetylation of TAF(I)68, a Subunit of TIF-IB/SL1, Activates RNA Polymerase I Transcription. EMBO J. 2001 ; 20 (6). 1353-1362 (Pubitemid 32233975)
38. Ponugoti B., Kim D. H., Xiao Z., Smith Z., Miao J., Zang M., Wu S. Y., Chiang C. M., Veenstra T. D., Kemper J. K.. SIRT1 Deacetylates and Inhibits SREBP-1C Activity in Regulation of Hepatic Lipid Metabolism. J. Biol. Chem. 2010 ; 285 (44). 33959-33970
39. Firestein R., Blander G., Michan S., Oberdoerffer P., Ogino S., Campbell J., Bhimavarapu A., Luikenhuis S., de Cabo R., Fuchs C., et al. The SIRT1 Deacetylase Suppresses Intestinal Tumorigenesis and Colon Cancer Growth. PloS One. 2008 ; 3 (4). e2020
40. Yeung F., Hoberg J. E., Ramsey C. S., Keller M. D., Jones D. R., Frye R. A., Mayo M. W.. Modulation of NF-kappaB-Dependent Transcription and Cell Survival by the SIRT1 Deacetylase. EMBO J. 2004 ; 23 (12). 2369-2380 (Pubitemid 38954844)
41. Schug T. T., Xu Q., Gao H., Peres-da-Silva A., Draper D. W., Fessler M. B., Purushotham A., Li X.. Myeloid Deletion of SIRT1 Induces Inflammatory Signaling in Response to Environmental Stress. Mol. Cell. Biol. 2010 ; 30 (19). 4712-4721
42. Rodgers J. T., Lerin C., Haas W., Gygi S. P., Spiegelman B. M., Puigserver P.. Nutrient Control of Glucose Homeostasis through a Complex of PGC-1alpha and SIRT1. Nature. 2005 ; 434 (7029). 113-118 (Pubitemid 40349395)
43. Nakahata Y., Kaluzova M., Grimaldi B., Sahar S., Hirayama J., Chen D., Guarente L. P., Sassone-Corsi P.. The NAD+-Dependent Deacetylase SIRT1 Modulates CLOCK-Mediated Chromatin Remodeling and Circadian Control. Cell. 2008 ; 134 (2). 329-340 (Pubitemid 352010336)
44. Asher G., Gatfield D., Stratmann M., Reinke H., Dibner C., Kreppel F., Mostoslavsky R., Alt F. W., Schibler U.. SIRT1 Regulates Circadian Clock Gene Expression through PER2 Deacetylation. Cell. 2008 ; 134 (2). 317-328 (Pubitemid 352024391)
45. Jeong J., Juhn K., Lee H., Kim S. H., Min B. H., Lee K. M., Cho M. H., Park G. H., Lee K. H.. SIRT1 Promotes DNA Repair Activity and Deacetylation of Ku70. Exp. Mol. Med. 2007 ; 39 (1). 8-13 (Pubitemid 46356001)
46. Fan W., Luo J.. SIRT1 Regulates UV-Induced DNA Repair through Deacetylating XPA. Mol. Cell. 2010 ; 39 (2). 247-258
47. Kume S., Haneda M., Kanasaki K., Sugimoto T., Araki S., Isshiki K., Isono M., Uzu T., Guarente L., Kashiwagi A., et al. SIRT1 Inhibits Transforming Growth Factor Beta-Induced Apoptosis in Glomerular Mesangial Cells via Smad7 Deacetylation. J. Biol. Chem. 2007 ; 282 (1). 151-158 (Pubitemid 47076643)
48. Zhang Y., Zhang M., Dong H., Yong S., Li X., Olashaw N., Kruk P. A., Cheng J. Q., Bai W., Chen J., et al. Deacetylation of Cortactin by SIRT1 Promotes Cell Migration. Oncogene. 2009 ; 28 (3). 445-460
49. Zhang J.. The Direct Involvement of SirT1 in Insulin-Induced Insulin Receptor Substrate-2 Tyrosine Phosphorylation. J. Biol. Chem. 2007 ; 282 (47). 34356-34364 (Pubitemid 350159485)
50. Li Y., Xu W., McBurney M. W., Longo V. D.. SirT1 Inhibition Reduces IGF-I/IRS-2/Ras/ERK1/2 Signaling and Protects Neurons. Cell. Metab. 2008 ; 8 (1). 38-48 (Pubitemid 351859225)
51. Min S. W., Cho S. H., Zhou Y., Schroeder S., Haroutunian V., Seeley W. W., Huang E. J., Shen Y., Masliah E., Mukherjee C., et al. Acetylation of Tau Inhibits Its Degradation and Contributes to Tauopathy. Neuron. 2010 ; 67 (6). 953-966
52. Yamamori T., DeRicco J., Naqvi A., Hoffman T. A., Mattagajasingh I., Kasuno K., Jung S. B., Kim C. S., Irani K.. SIRT1 Deacetylates APE1 and Regulates Cellular Base Excision Repair. Nucleic Acids Res. 2010 ; 38 (3). 832-845
53. Pediconi N., Guerrieri F., Vossio S., Bruno T., Belloni L., Schinzari V., Scisciani C., Fanciulli M., Levrero M.. hSirT1-Dependent Regulation of the PCAF-E2F1-p73 Apoptotic Pathway in Response to DNA Damage. Mol. Cell. Biol. 2009 ; 29 (8). 1989-1998
54. Wang J., Chen J.. SIRT1 Regulates Autoacetylation and Histone Acetyltransferase Activity of TIP60. J. Biol. Chem. 2010 ; 285 (15). 11458-11464
55. Pagans S., Pedal A., North B. J., Kaehlcke K., Marshall B. L., Dorr A., Hetzer-Egger C., Henklein P., Frye R., McBurney M. W., et al. SIRT1 Regulates HIV Transcription via Tat Deacetylation. PLoS Biol. 2005 ; 3 (2). e41
56. Bouras T., Fu M., Sauve A. A., Wang F., Quong A. A., Perkins N. D., Hay R. T., Gu W., Pestell R. G.. SIRT1 Deacetylation and Repression of p300 Involves Lysine Residues 1020/1024 within the Cell Cycle Regulatory Domain 1. J. Biol. Chem. 2005 ; 280 (11). 10264-10276 (Pubitemid 40395882)
57. Vaquero A., Scher M., Erdjument-Bromage H., Tempst P., Serrano L., Reinberg D.. SIRT1 Regulates the Histone Methyl-Transferase SUV39H1 during Heterochromatin Formation. Nature. 2007 ; 450 (7168). 440-444 (Pubitemid 350126745)
58. Hallows W. C., Lee S., Denu J. M.. Sirtuins Deacetylate and Activate Mammalian Acetyl-CoA Synthetases. Proc. Natl. Acad. Sci. U. S. A. 2006 ; 103 (27). 10230-10235 (Pubitemid 44051149)
59. North B. J., Sinclair D. A.. Sirtuins: A Conserved Key Unlocking AceCS Activity. Trends Biochem. Sci. 2007 ; 32 (1). 1-4 (Pubitemid 46038733)
60. Han L., Zhou R., Niu J., McNutt M. A., Wang P., Tong T.. SIRT1 Is Regulated by a PPARγ-SIRT1 Negative Feedback Loop Associated with Senescence. Nucleic Acids Res. 2010 ; 38 (21). 7458-7471
61. Kim M. Y., Woo E. M., Chong Y. T., Homenko D. R., Kraus W. L.. Acetylation of Estrogen Receptor Alpha by p300 at Lysines 266 and 268 Enhances the Deoxyribonucleic Acid Binding and Transactivation Activities of the Receptor. Mol. Endocrinol. 2006 ; 20 (7). 1479-1493 (Pubitemid 43967558)
62. Fu M., Liu M., Sauve A. A., Jiao X., Zhang X., Wu X., Powell M. J., Yang T., Gu W., Avantaggiati M. L., et al. Hormonal Control of Androgen Receptor Function through SIRT1. Mol. Cell. Biol. 2006 ; 26 (21). 8122-8135 (Pubitemid 44631010)
63. Li X., Zhang S., Blander G., Tse J. G., Krieger M., Guarente L.. SIRT1 Deacetylates and Positively Regulates the Nuclear Receptor LXR. Mol. Cell. 2007 ; 28 (1). 91-106 (Pubitemid 47531974)
64. Blander G., Olejnik J., Krzymanska-Olejnik E., McDonagh T., Haigis M., Yaffe M. B., Guarente L.. SIRT1 Shows No Substrate Specificity In Vitro. J. Biol. Chem. 2005 ; 280 (11). 9780-9785 (Pubitemid 40395823)
65. Hisahara S., Chiba S., Matsumoto H., Tanno M., Yagi H., Shimohama S., Sato M., Horio Y.. Histone Deacetylase SIRT1 Modulates Neuronal Differentiation by Its Nuclear Translocation. Proc. Natl. Acad. Sci. U. S. A. 2008 ; 105 (40). 15599-15604
66. Sugino T., Maruyama M., Tanno M., Kuno A., Houkin K., Horio Y.. Protein Deacetylase SIRT1 in the Cytoplasm Promotes Nerve Growth Factor-Induced Neurite Outgrowth in PC12 Cells. FEBS Lett. 2010 ; 584 (13). 2821-2826
67. Holness M. J., Caton P. W., Sugden M. C.. Acute and Long-Term Nutrient-Led Modifications of Gene Expression: Potential Role of SIRT1 as a Central Co-ordinator of Short and Longer-Term Programming of Tissue Function. Nutrition. 2010 ; 26 (5). 491-501
68. Sasaki T., Kitamura T.. Roles of FoxO1 and Sirt1 in the Central Regulation of Food Intake. Endocr. J. 2010 ; 57 (11). 939-946
69. Bellet M. M., Sassone-Corsi P.. Mammalian Circadian Clock and Metabolism: The Epigenetic Link. J. Cell. Sci 123. 2010 ; (Pt 22). 3837-3848
70. Yang T., Fu M., Pestell R., Sauve A. A.. SIRT1 and Endocrine Signaling. Trends Endocrinol. Metab. 2006 ; 17 (5). 186-191 (Pubitemid 43974972)
71. Dominy J. E., Lee Y., Gerhart-Hines Z., Puigserver P.. Nutrient-Dependent Regulation of PGC-1alpha's Acetylation State and Metabolic Function through the Enzymatic Activities of Sirt1/GCN5. Biochim. Biophys. Acta. 2010 ; 1804 (8). 1676-1683
72. Zhang T., Kraus W. L.. SIRT1-Dependent Regulation of Chromatin and Transcription: Linking NAD(+) Metabolism and Signaling to the Control of Cellular Functions. Biochim. Biophys. Acta. 2010 ; 1804 (8). 1666-1675
73. Li Y., Xu S., Giles A., Nakamura K., Lee J. W., Hou X., Donmez G., Li J., Luo Z., Walsh K., et al. Hepatic Overexpression of SIRT1 in Mice Attenuates Endoplasmic Reticulum Stress and Insulin Resistance in the Liver. FASEB J. 2011 ; 25 (5). 1664-1679
74. Sun C., Zhang F., Ge X., Yan T., Chen X., Shi X., Zhai Q.. SIRT1 Improves Insulin Sensitivity under Insulin-Resistant Conditions by Repressing PTP1B. Cell. Metab. 2007 ; 6 (4). 307-319 (Pubitemid 47468091)
75. Bordone L., Motta M. C., Picard F., Robinson A., Jhala U. S., Apfeld J., McDonagh T., Lemieux M., McBurney M., Szilvasi A., et al. Sirt1 Regulates Insulin Secretion by Repressing UCP2 in Pancreatic Beta Cells. PLoS Biol. 2006 ; 4 (2). e31
76. Haigis M. C., Guarente L. P.. Mammalian Sirtuins: Emerging Roles in Physiology, Aging, and Calorie Restriction. Genes Dev. 2006 ; 20 (21). 2913-2921 (Pubitemid 44771725)
77. Liang F., Kume S., Koya D.. SIRT1 and Insulin Resistance. Nat. Rev. Endocrinol. 2009 ; 5 (7). 367-373
78. Chen J., Zhou Y., Mueller-Steiner S., Chen L. F., Kwon H., Yi S., Mucke L., Gan L.. SIRT1 Protects against Microglia-Dependent Amyloid-Beta Toxicity through Inhibiting NF-kappaB Signaling. J. Biol. Chem. 2005 ; 280 (48). 40364-40374 (Pubitemid 41779174)
79. Qin W., Yang T., Ho L., Zhao Z., Wang J., Chen L., Zhao W., Thiyagarajan M., MacGrogan D., Rodgers J. T., et al. Neuronal SIRT1 Activation as a Novel Mechanism Underlying the Prevention of Alzheimer Disease Amyloid Neuropathology by Calorie Restriction. J. Biol. Chem. 2006 ; 281 (31). 21745-21754 (Pubitemid 44181878)
80. Donmez G., Wang D., Cohen D. E., Guarente L.. SIRT1 Suppresses Beta-Amyloid Production by Activating the Alpha-Secretase Gene ADAM10. Cell. 2010 ; 142 (2). 320-332
81. Wang J., Fivecoat H., Ho L., Pan Y., Ling E., Pasinetti G. M.. The Role of Sirt1: At the Crossroad between Promotion of Longevity and Protection against Alzheimer's Disease Neuropathology. Biochim. Biophys. Acta. 2010 ; 1804 (8). 1690-1694
82. Kim D., Nguyen M. D., Dobbin M. M., Fischer A., Sananbenesi F., Rodgers J. T., Delalle I., Baur J. A., Sui G., Armour S. M., et al. SIRT1 Deacetylase Protects against Neurodegeneration in Models for Alzheimer's Disease and Amyotrophic Lateral Sclerosis. EMBO J. 2007 ; 26 (13). 3169-3179 (Pubitemid 47057498)
83. Yang Z., Kahn B. B., Shi H., Xue B. Z.. Macrophage alpha1 AMP-Activated Protein Kinase (alpha1AMPK) Antagonizes Fatty Acid-Induced Inflammation through SIRT1. J. Biol. Chem. 2010 ; 285 (25). 19051-19059
84. Rajendrasozhan S., Yang S. R., Kinnula V. L., Rahman I.. SIRT1, an Antiinflammatory and Antiaging Protein, Is Decreased in Lungs of Patients with Chronic Obstructive Pulmonary Disease. Am. J. Respir. Crit. Care Med. 2008 ; 177 (8). 861-870 (Pubitemid 351600664)
85. Zhang R., Chen H. Z., Liu J. J., Jia Y. Y., Zhang Z. Q., Yang R. F., Zhang Y., Xu J., Wei Y. S., Liu D. P., et al. SIRT1 Suppresses Activator Protein-1 Transcriptional Activity and Cyclooxygenase-2 Expression in Macrophages. J. Biol. Chem. 2010 ; 285 (10). 7097-7110
86. Planavila A., Iglesias R., Giralt M., Villarroya F.. Sirt1 Acts in Association with PPAR{alpha} to Protect the Heart from Hypertrophy, Metabolic Dysregulation, and Inflammation. Cardiovasc. Res. 2011 ; 90 (2). 276-284
87. Zhang Z., Lowry S. F., Guarente L., Haimovich B.. Roles of SIRT1 in the Acute and Restorative Phases following Induction of Inflammation. J. Biol. Chem. 2010 ; 285 (53). 41391-41401
88. Liu T. F., Yoza B. K., El Gazzar M., Vachharajani V. T., McCall C. E.. NAD+-Dependent SIRT1 Deacetylase Participates in Epigenetic Reprogramming during Endotoxin Tolerance. J. Biol. Chem. 2011 ; 286 (11). 9856-9864
89. Kwon H. S., Brent M. M., Getachew R., Jayakumar P., Chen L. F., Schnoelzer M., McBurney M. W., Marmorstein R., Greene W. C., Ott M.. Human Immunodeficiency Virus Type 1 Tat Protein Inhibits the SIRT1 Deacetylase and Induces T Cell Hyperactivation. Cell Host Microbe. 2008 ; 3 (3). 158-167 (Pubitemid 351325758)
90. Beier U. H., Wang L., Bhatti T. R., Liu Y., Han R., Ge G., Hancock W. W.. Sirtuin-1 Targeting Promotes Foxp3+ T-Regulatory Cell Function and Prolongs Allograft Survival. Mol. Cell. Biol. 2011 ; 31 (5). 1022-1029
91. Wang B., Hasan M. K., Alvarado E., Yuan H., Wu H., Chen W. Y.. NAMPT Overexpression in Prostate Cancer and Its Contribution to Tumor Cell Survival and Stress Response. Oncogene. 2011 ; 30 (8). 907-921
92. Chen J., Zhang B., Wong N., Lo A. W., To K. F., Chan A. W., Ng M. H., Ho C. Y., Cheng S. H., Lai P. B., et al. Sirtuin 1 Is Upregulated in a Subset of hepatocellular Carcinomas Where It Is Essential for Telomere Maintenance and Tumor Cell Growth. Cancer Res. 2011 ; 71 (12). 4138-4149
93. Jung-Hynes B., Nihal M., Zhong W., Ahmad N.. Role of Sirtuin Histone Deacetylase SIRT1 in Prostate Cancer: A Target for Prostate Cancer Management via Its Inhibition?. J. Biol. Chem. 2009 ; 284 (6). 3823-3832
94. Jang K. Y., Kim K. S., Hwang S. H., Kwon K. S., Kim K. R., Park H. S., Park B. H., Chung M. J., Kang M. J., Lee D. G., et al. Expression and Prognostic Significance of SIRT1 in Ovarian Epithelial Tumours. Pathology. 2009 ; 41 (4). 366-371
95. Cha E. J., Noh S. J., Kwon K. S., Kim C. Y., Park B. H., Park H. S., Lee H., Chung M. J., Kang M. J., et al. Expression of DBC1 and SIRT1 Is Associated with Poor Prognosis of Gastric Carcinoma. Clin. Cancer Res. 2009 ; 15 (13). 4453-4459
96. Nosho K., Shima K., Irahara N., Kure S., Firestein R., Baba Y., Toyoda S., Chen L., Hazra A., Giovannucci E. L., et al. SIRT1 Histone Deacetylase Expression Is Associated with Microsatellite Instability and CpG Island Methylator Phenotype in Colorectal Cancer. Mod. Pathol. 2009 ; 22 (7). 922-932
97. Nihal M., Ndiaye M., Wood G. S., Ahmad N... Proceedings of the 102nd Annual Meeting of the AACR ; Orlando, FL ;..
98. Hoffmann M. J., Engers R., Florl A. R., Otte A. P., Muller M., Schulz W. A.. Expression Changes in EZH2, but Not in BMI-1, SIRT1, DNMT1 or DNMT3B Are Associated with DNA Methylation Changes in Prostate Cancer. Cancer Biol. Ther. 2007 ; 6 (9). 1403-1412 (Pubitemid 351590350)
99. Kabra N., Li Z., Chen L., Li B., Zhang X., Wang C., Yeatman T., Coppola D., Chen J.. SirT1 Is an Inhibitor of Proliferation and Tumor Formation in Colon Cancer. J. Biol. Chem. 2009 ; 284 (27). 18210-18217
100. Herranz D., Serrano M.. SIRT1: Recent Lessons from Mouse Models. Nat. Rev. Cancer. 2010 ; 10 (12). 819-823
101. Boily G., He X. H., Pearce B., Jardine K., McBurney M. W.. SirT1-Null Mice Develop Tumors at Normal Rates but Are Poorly Protected by Resveratrol. Oncogene. 2009 ; 28 (32). 2882-2893
102. Powell M. J., Casimiro M. C., Cordon-Cardo C., He X., Yeow W. S., Wang C., McCue P. A., McBurney M. W., Pestell R. G.. Disruption of a Sirt1-Dependent Autophagy Checkpoint in the Prostate Results in Prostatic Intraepithelial Neoplasia Lesion Formation. Cancer Res. 2011 ; 71 (3). 964-975
103. Ming M., Shea C. R., Guo X., Li X., Soltani K., Han W., He Y. Y.. Regulation of Global Genome Nucleotide Excision Repair by SIRT1 through Xeroderma Pigmentosum C. Proc. Natl. Acad. Sci. U. S. A. 2010 ; 107 (52). 22623-22628
104. Yuan Z., Seto E.. A Functional Link between SIRT1 Deacetylase and NBS1 in DNA Damage Response. Cell Cycle. 2007 ; 6 (23). 2869-2871
105. Ghosh H. S., McBurney M., Robbins P. D.. SIRT1 Negatively Regulates the Mammalian Target of Rapamycin. PLoS One. 2010 ; 5 (2). e9199
106. Back J. H., Rezvani H. R., Zhu Y., Guyonnet-Duperat V., Athar M., Ratner D., Kim A. L.. Cancer Cell Survival following DNA Damage-Mediated Premature Senescence Is Regulated by Mammalian Target of Rapamycin (mTOR)-Dependent Inhibition of Sirtuin 1. J. Biol. Chem. 2011 ; 286 (21). 19100-19108
107. Xiang T., Jia Y., Sherris D., Li S., Wang H., Lu D., Yang Q.. Targeting the Akt/mTOR Pathway in Brca1-Deficient Cancers. Oncogene. 2011 ; 30 (21). 2443-2450
108. Wang R. H., Zheng Y., Kim H. S., Xu X., Cao L., Luhasen T., Lee M. H., Xiao C., Vassilopoulos A., Chen W., et al. Interplay among BRCA1, SIRT1, and Survivin during BRCA1-Associated Tumorigenesis. Mol. Cell. 2008 ; 32 (1). 11-20
109. Lu R., Bian F., Zhang X., Qi H., Chuang E. Y., et al. The Beta-Catenin/Tcf4/Survivin Signaling Maintains a Less Differentiated Phenotype and High Proliferative Capacity of Human Corneal Epithelial Progenitor Cells. Int. J. Biochem. Cell. Biol. 2011 ; 43 (5). 751-759
110. Holloway K. R., Calhoun T. N., Saxena M., Metoyer C. F., Kandler E. F., Rivera C. A., Pruitt K.. SIRT1 Regulates Dishevelled Proteins and Promotes Transient and Constitutive Wnt Signaling. Proc. Natl. Acad. Sci. U. S. A. 2010 ; 107 (20). 9216-9221
111. Papp B., Plath K.. Reprogramming to Pluripotency: Stepwise Resetting of the Epigenetic Landscape. Cell. Res. 2011 ; 21 (3). 486-501
112. Yuan J., Minter-Dykhouse K., Lou Z.. A c-Myc-SIRT1 Feedback Loop Regulates Cell Growth and Transformation. J. Cell Biol. 2009 ; 185 (2). 203-211
113. Hayashi M., Tokuchi Y., Hashimoto T., Hayashi S., Nishida K., Ishikawa I., Nakagawa K., Tsuchiya S., Okamura S., Tsuchiya E.. Reduced HIC-1 Gene Expression in Non-Small Cell Lung Cancer and Its Clinical Significance 2001. Anticancer Res 21.: 535-540
114. Fujii H., Biel M. A., Zhou W., Weitzman S. A., Baylin S. B., Gabrielson E.. Methylation of the HIC-1 Candidate Tumor Suppressor Gene in Human Breast Cancer. Oncogene. 1998 ; 16 (16). 2159-2164 (Pubitemid 28211691)
115. Chen W. Y., Wang D. H., Yen R. C., Luo J., Gu W., Baylin S. B.. Tumor Suppressor HIC1 Directly Regulates SIRT1 to Modulate p53-Dependent DNA-Damage Responses. Cell. 2005 ; 123 (3). 437-448 (Pubitemid 41546674)
116. Tseng R. C., Lee C. C., Hsu H. S., Tzao C., Wang Y. C.. Distinct HIC1-SIRT1-p53 Loop Deregulation in Lung Squamous Carcinoma and Adenocarcinoma Patients. Neoplasia. 2009 ; 11 (8). 763-770
117. Mohammad H. P., Zhang W., Prevas H. S., Leadem B. R., Zhang M., Herman J. G., Hooker C. M., Watkins D. N., Karim B., Huso D. L., et al. Loss of a Single Hic1 Allele Accelerates Polyp Formation in Apc(Delta716) Mice. Oncogene. 2011 ; 30 (23). 2659-2669
118. Marshall G. M., Liu P. Y., Gherardi S., Scarlett C. J., Bedalov A., Xu N., Iraci N., Valli E., Ling D., Thomas W., van Bekkum M., Sekyere E., Jankowski K., Trahair T., Mackenzie K. L., Haber M., Norris M. D., Biankin A. V., Perini G., Liu T.. SIRT1 Promotes N-Myc Oncogenesis through a Positive Feedback Loop Involving the Effects of MKP3 and ERK on N-Myc Protein Stability. PLoS Genet. 2011 ; 7 (6). e1002135
119. Serrano M.. In. Proceedings of the 102nd Annual Meeting of the AACR ; Orlando, FL ;..
120. Olmos Y., Brosens J. J., Lam E. W.. Interplay between SIRT Proteins and Tumour Suppressor Transcription Factors in Chemotherapeutic Resistance of Cancer. Drug Resist. Updat. 2011 ; 14 (1). 35-44
121. Eades G., Yao Y., Yang M., Zhang Y., Chumsri S., Zhou Q.. MiR-200a Regulates SIRT1 and EMT-Like Transformation in Mammary Epithelial Cells. J. Biol. Chem. 2011 ; 286 (29). 25992-26002
122. Inoue Y., Iemura S., Natsume T., Miyazawa K., Imamura T.. Suppression of p53 Activity through the Cooperative Action of Ski and Histone Deacetylase SIRT1. J. Biol. Chem. 2011 ; 286 (8). 6311-6320
123. Ford J., Jiang M., Milner J.. Cancer-Specific Functions of SIRT1 Enable Human Epithelial Cancer Cell Growth and Survival. Cancer Res. 2005 ; 65 (22). 10457-10463 (Pubitemid 41743740)
124. Stenzinger A., Goppert B., Kamphues C., Sinn B., Bahra M., Neuhaus P., Weichert W.. SIRT1 overexpression in pancreatic adenocarcinomas correlates with shortened patient survival and small molecule inhibition as well as target knockdown of SIRT1 induces growth arrest and apoptosis in pancreatic cancer cells. 102nd Annual Meeting of the AACR 2011 ; ;..
125. Peck B., Chen C. Y., Ho K. K., Di Fruscia P., Myatt S. S., Coombes R. C., Fuchter M. J., Hsiao C. D., Lam E. W.. SIRT Inhibitors Induce Cell Death and p53 Acetylation through Targeting Both SIRT1 and SIRT2. Mol. Cancer Ther. 2010 ; 9 (4). 844-855
126. Ota H., Tokunaga E., Chang K., Hikasa M., Iijima K., Eto M., Kozaki K., Akishita M., Ouchi Y., Kaneki M., et al. Sirt1 Inhibitor, Sirtinol, Induces Senescence-Like Growth Arrest with Attenuated Ras-MAPK Signaling in Human Cancer Cells. Oncogene. 2006 ; 25 (2). 176-185 (Pubitemid 43083679)
127. O'Hagan H. M., Mohammad H. P., Baylin S. B.. Double Strand Breaks Can Initiate Gene Silencing and SIRT1-Dependent Onset of DNA Methylation in an Exogenous Promoter CpG Island. PLoS Genet. 2008 ; 4 (8). e1000155
128. Kuzmichev A., Margueron R., Vaquero A., Preissner T. S., Scher M., Kirmizis A., Ouyang X., Brockdorff N., Abate-Shen C., Farnham P., Reinberg D.. Composition and Histone Substrates of Polycomb Repressive Group Complexes Change during Cellular Differentiation. Proc. Natl. Acad. Sci. U. S. A. 2005 ; 102 (6). 1859-1864 (Pubitemid 40261977)
129. Sun Y., Jiang X., Price B. D.. Tip60: Connecting Chromatin to DNA Damage Signaling. Cell Cycle. 2010 ; 9 (5). 930-936
130. Ikura T., Ogryzko V. V., Grigoriev M., Groisman R., Wang J., Horikoshi M., Scully R., Qin J., Nakatani Y.. Involvement of the TIP60 Histone Acetylase Complex in DNA Repair and Apoptosis. Cell. 2000 ; 102 (4). 463-473
131. Yamagata K., Kitabayashi I.. Sirt1 Physically Interacts with Tip60 and Negatively Regulates Tip60-Mediated Acetylation of H2AX. Biochem. Biophys. Res. Commun. 2009 ; 390 (4). 1355-1360
132. Wang C., Chen L., Hou X., Li Z., Kabra N., Ma Y., Nemoto S., Finkel T., Gu W., Cress W. D., et al. Interactions between E2F1 and SirT1 Regulate Apoptotic Response to DNA Damage. Nat. Cell. Biol. 2006 ; 8 (9). 1025-1031 (Pubitemid 44314735)
133. Potente M., Ghaeni L., Baldessari D., Mostoslavsky R., Rossig L., Dequiedt F., Haendeler J., Mione M., Dejana E., Alt F. W., et al. SIRT1 Controls Endothelial Angiogenic Functions during Vascular Growth. Genes Dev. 2007 ; 21 (20). 2644-2658 (Pubitemid 47607673)
134. Li Y., Tondravi M., Liu J., Smith E., Haudenschild C. C., Kaczmarek M., Zhan X.. Cortactin Potentiates Bone Metastasis of Breast Cancer Cells. Cancer Res. 2001 ; 61 (18). 6906-6911 (Pubitemid 32896517)
135. Luo M. L., Shen X. M., Zhang Y., Wei F., Xu X., Sun Y. T., Zhan Q. M., Wu M., Wang M. R.. Amplification and Overexpression of CTTN (EMS1) Contribute to the Metastasis of Esophageal Squamous Cell Carcinoma by Promoting Cell Migration and Anoikis Resistance. Cancer Res. 2006 ; 66 (24). 11690-11699 (Pubitemid 46094181)
136. Marcotte P. A., Richardson P. L., Guo J., Barrett L. W., Xu N., Gunasekera A., Glaser K. B.. Fluorescence Assay of SIRT Protein Deacetylases Using an Acetylated Peptide Substrate and a Secondary Trypsin Reaction. Anal. Biochem. 2004 ; 332 (1). 90-99 (Pubitemid 39099475)
137. Bitterman K. J., Anderson R. M., Cohen H. Y., Latorre-Esteves M., Sinclair D. A.. Inhibition of Silencing and Accelerated Aging by Nicotinamide, a Putative Negative Regulator of Yeast sir2 and Human SIRT1. J. Biol. Chem. 2002 ; 277 (47). 45099-45107 (Pubitemid 36159111)
138. Feng Y., Wu J., Chen L., Luo C., Shen X., Chen K., Jiang H., Liu D.. A Fluorometric Assay of SIRT1 Deacetylation Activity through Quantification of Nicotinamide Adenine Dinucleotide. Anal. Biochem. 2009 ; 395 (2). 205-210
139. Wegener D., Hildmann C., Riester D., Schwienhorst A.. Improved Fluorogenic Histone Deacetylase Assay for High-Throughput-Screening Applications. Anal. Biochem. 2003 ; 321 (2). 202-208 (Pubitemid 37162740)
140. Liu Y., Gerber R., Wu J., Tsuruda T., McCarter J. D.. High-Throughput Assays for Sirtuin Enzymes: A Microfluidic Mobility Shift Assay and a Bioluminescence Assay. Anal. Biochem. 2008 ; 378 (1). 53-59
141. Milne J. C., Lambert P. D., Schenk S., Carney D. P., Smith J. J., Gagne D. J., Jin L., Boss O., Perni R. B., Vu C. B., et al. Small Molecule Activators of SIRT1 as Therapeutics for the Treatment of Type 2 Diabetes. Nature. 2007 ; 450 (7170). 712-716 (Pubitemid 350207685)
142. Rye P. T., Frick L. E., Ozbal C. C., LaMarr W. A.. Advances in label-free screening approaches for studying histone acetyltransferases. J. Biomol. Screen. 2011 ; 16 (10). 1186-1195
143. Fan Y., Hense M., Ludewig R., Weisgerber C., Scriba G. K.. Capillary Electrophoresis-Based Sirtuin Assay Using Non-Peptide Substrates. J. Pharm. Biomed. Anal. 2011 ; 54 (4). 772-778
144. Jackson M. D., Denu J. M.. Structural Identification of 2′- and 3′-O-Acetyl-ADP-Ribose as Novel Metabolites Derived from the Sir2 Family of Beta -NAD+-Dependent Histone/Protein Deacetylases. J. Biol. Chem. 2002 ; 277 (21). 18535-18544 (Pubitemid 34952404)
145. Grozinger C. M., Chao E. D., Blackwell H. E., Moazed D., Schreiber S. L.. Identification of a Class of Small Molecule Inhibitors of the Sirtuin Family of NAD-Dependent Deacetylases by Phenotypic Screening. J. Biol. Chem. 2001 ; 276 (42). 38837-38843
146. Bedalov A., Gatbonton T., Irvine W. P., Gottschling D. E., Simon J. A.. Identification of a Small Molecule Inhibitor of Sir2p. Proc. Natl. Acad. Sci. U. S. A. 2001 ; 98 (26). 15113-15118 (Pubitemid 34013978)
147. Borra M. T., Denu J. M.. Quantitative Assays for Characterization of the Sir2 Family of NAD(+)-Dependent Deacetylases. Methods Enzymol. 2004 ; 376: 171-187 (Pubitemid 38200178)
148. Howitz K. T., Bitterman K. J., Cohen H. Y., Lamming D. W., Lavu S., Wood J. G., Zipkin R. E., Chung P., Kisielewski A., Zhang L. L., et al. Small Molecule Activators of Sirtuins Extend Saccharomyces cerevisiae Lifespan. Nature. 2003 ; 425 (6954). 191-196 (Pubitemid 37150899)
149. de Boer V. C., de Goffau M. C., Arts I. C., Hollman P. C., Keijer J.. SIRT1 Stimulation by Polyphenols Is Affected by Their Stability and Metabolism. Mech. Ageing Dev. 2006 ; 127 (7). 618-627 (Pubitemid 43729534)
150. Borra M. T., Smith B. C., Denu J. M.. Mechanism of Human SIRT1 Activation by Resveratrol. J. Biol. Chem. 2005 ; 280 (17). 17187-17195 (Pubitemid 41389185)
151. Kaeberlein M., McDonagh T., Heltweg B., Hixon J., Westman E. A., Caldwell S. D., Napper A., Curtis R., DiStefano P. S., Fields S., et al. Substrate-Specific Activation of Sirtuins by Resveratrol. J. Biol. Chem. 2005 ; 280 (17). 17038-17045 (Pubitemid 41389166)
152. Pacholec M., Bleasdale J. E., Chrunyk B., Cunningham D., Flynn D., Griffith D. A., Griffor M., Loulakis P., Pabst B., Qiu X., et al. SRT1720, SRT2183, SRT1460, and Resveratrol Are Not Direct Activators of SIRT1. J. Biol. Chem. 2010 ; 285 (11). 8340-8351
153. Huber J. L., McBurney M. W., Distefano P. S., McDonagh T.. SIRT1-Independent Mechanisms of the Putative Sirtuin Enzyme Activators SRT1720 and SRT2183. Future Med. Chem. 2010 ; 2 (12). 1751-1759
154. Geahlen R. L., McLaughlin J. L.. Piceatannol (3,4,3′,5′- Tetrahydroxy-Trans-Stilbene) Is a Naturally Occurring Protein-Tyrosine Kinase Inhibitor. Biochem. Biophys. Res. Commun. 1989 ; 165 (1). 241-245 (Pubitemid 20012481)
155. Dadi P. K., Ahmad M., Ahmad Z.. Inhibition of ATPase Activity of Escherichia coli ATP Synthase by Polyphenols. Int. J. Biol. Macromol. 2009 ; 45 (1). 72-79
156. Napper A. D., Hixon J., McDonagh T., Keavey K., Pons J. F., Barker J., Yau W. T., Amouzegh P., Flegg A., Hamelin E., et al. Discovery of Indoles as Potent and Selective Inhibitors of the Deacetylase SIRT1. J. Med. Chem. 2005 ; 48 (25). 8045-8054 (Pubitemid 41798434)
157. Solomon J. M., Pasupuleti R., Xu L., McDonagh T., Curtis R., DiStefano P. S., Huber L. J.. Inhibition of SIRT1 Catalytic Activity Increases p53 Acetylation but Does Not Alter Cell Survival following DNA Damage. Mol. Cell. Biol. 2006 ; 26 (1). 28-38
158. Joubel A., Chalkley R. J., Medzihradszky K. F., Hondermarck H., Burlingame A. L.. Identification of New p53 Acetylation Sites in COS-1 Cells. Mol. Cell. Proteomics. 2009 ; 8 (6). 1167-1173
159. Vakhrusheva O., Smolka C., Gajawada P., Kostin S., Boettger T., Kubin T., Braun T., Bober E.. Sirt7 Increases Stress Resistance of Cardiomyocytes and Prevents Apoptosis and Inflammatory Cardiomyopathy in Mice. Circ. Res. 2008 ; 102 (6). 703-710 (Pubitemid 351457857)
160. Heltweg B., Gatbonton T., Schuler A. D., Posakony J., Li H., Goehle S., Kollipara R., Depinho R. A., Gu Y., Simon J. A., et al. Antitumor Activity of a Small-Molecule Inhibitor of Human Silent Information Regulator 2 Enzymes. Cancer Res. 2006 ; 66 (8). 4368-4377
161. Lara E., Mai A., Calvanese V., Altucci L., Lopez-Nieva P., Martinez-Chantar M. L., Varela-Rey M., Rotili D., Nebbioso A., Ropero S., et al. Salermide, a Sirtuin Inhibitor with a Strong Cancer-Specific Proapoptotic Effect. Oncogene. 2009 ; 28 (6). 781-791
162. Kalle A. M., Mallika A., Badiger J., Alinakhi , Talukdar P., Sachchidanand . Inhibition of SIRT1 by a Small Molecule Induces Apoptosis in Breast Cancer Cells. Biochem. Biophys. Res. Commun. 2010 ; 401 (1). 13-19
163. Trapp J., Meier R., Hongwiset D., Kassack M. U., Sippl W., Jung M.. Structure-Activity Studies on Suramin Analogues as Inhibitors of NAD+-Dependent Histone Deacetylases (Sirtuins). ChemMedChem. 2007 ; 2 (10). 1419-1431
164. Lain S., Hollick J. J., Campbell J., Staples O. D., Higgins M., Aoubala M., McCarthy A., Appleyard V., Murray K. E., Baker L., et al. Discovery, In Vivo Activity, and Mechanism of Action of a Small-Molecule p53 Activator. Cancer Cell. 2008 ; 13 (5). 454-463 (Pubitemid 351609441)
165. Huhtiniemi T., Suuronen T., Lahtela-Kakkonen M., Bruijn T., Jääskeläinen S., Poso A., Salminen A., Leppänen J., Jarho E.. N(epsilon)-Modified Lysine Containing Inhibitors for SIRT1 and SIRT2. Bioorg. Med. Chem. 2010 ; 18 (15). 5616-5625
166. Kiviranta P. H., Suuronen T., Wallen E. A., Leppanen J., Tervonen J., Kyrylenko S., Salminen A., Poso A., Jarho E. M.. N(epsilon)-Thioacetyl-Lysine- Containing Tri-, Tetra-, and Pentapeptides as SIRT1 and SIRT2 Inhibitors. J. Med. Chem. 2009 ; 52 (7). 2153-2156
167. Medda F., Russell R. J., Higgins M., McCarthy A. R., Campbell J., Slawin A. M., Lane D. P., Lain S., Westwood N. J.. Novel Cambinol Analogs as Sirtuin Inhibitors: Synthesis, Biological Evaluation, and Rationalization of Activity. J. Med. Chem. 2009 ; 52 (9). 2673-2682
168. Sanders B. D., Jackson B., Brent M., Taylor A. M., Dang W., Berger S. L., Schreiber S. L., Howitz K., Marmorstein R.. Identification and Characterization of Novel Sirtuin Inhibitor Scaffolds. Bioorg. Med. Chem. 2009 ; 17 (19). 7031-7041
169. Zhao K., Chai X., Clements A., Marmorstein R.. Structure and Autoregulation of the Yeast Hst2 Homolog of Sir2. Nat. Struct. Biol. 2003 ; 10 (10). 864-871 (Pubitemid 37187660)
170. Zhao K., Harshaw R., Chai X., Marmorstein R.. Structural Basis for Nicotinamide Cleavage and ADP-Ribose Transfer by NAD(+)-Dependent Sir2 Histone/Protein Deacetylases. Proc. Natl. Acad. Sci. U. S. A. 2004 ; 101 (23). 8563-8568 (Pubitemid 38745810)
171. Sanders B. D., Zhao K., Slama J. T., Marmorstein R.. Structural Basis for Nicotinamide Inhibition and Base Exchange in Sir2 Enzymes. Mol. Cell. 2007 ; 25 (3). 463-472 (Pubitemid 46199287)
172. Zhao K., Chai X., Marmorstein R.. Structure and Substrate Binding Properties of cobB, a Sir2 Homolog Protein Deacetylase from. Escherichia coli. J. Mol. Biol. 2004 ; 337 (3). 731-741 (Pubitemid 38326887)
173. Hoff K. G., Avalos J. L., Sens K., Wolberger C.. Insights into the Sirtuin Mechanism from Ternary Complexes Containing NAD+ and Acetylated Peptide. Structure. 2006 ; 14 (8). 1231-1240 (Pubitemid 44176368)
174. Cosgrove M. S., Bever K., Avalos J. L., Muhammad S., Zhang X., Wolberger C.. The Structural Basis of Sirtuin Substrate Affinity. Biochemistry. 2006 ; 45 (24). 7511-7521 (Pubitemid 43894945)
175. Avalos J. L., Bever K. M., Wolberger C.. Mechanism of Sirtuin Inhibition by Nicotinamide: Altering the NAD(+) Cosubstrate Specificity of a Sir2 Enzyme. Mol. Cell. 2005 ; 17 (6). 855-868 (Pubitemid 40386946)
176. Min J., Landry J., Sternglanz R., Xu R. M.. Crystal Structure of a SIR2 Homolog-NAD Complex. Cell. 2001 ; 105 (2). 269-279 (Pubitemid 32429516)
177. Chang J. H., Kim H. C., Hwang K. Y., Lee J. W., Jackson S. P., Bell S. D., Cho Y.. Structural Basis for the NAD-Dependent Deacetylase Mechanism of Sir2. J. Biol. Chem. 2002 ; 277 (37). 34489-34498
178. Avalos J. L., Celic I., Muhammad S., Cosgrove M. S., Boeke J. D., Wolberger C.. Structure of a Sir2 Enzyme Bound to an Acetylated p53 Peptide. Mol. Cell. 2002 ; 10 (3). 523-535 (Pubitemid 35291068)
179. Lavu S., Boss O., Elliott P. J., Lambert P. D.. Sirtuins-Novel Therapeutic Targets to Treat Age-Associated Diseases. Nat. Rev. Drug Discov. 2008 ; 7 (10). 841-853
180. Finnin M. S., Donigian J. R., Pavletich N. P.. Structure of the Histone Deacetylase SIRT2. Nat. Struct. Biol. 2001 ; 8 (7). 621-625 (Pubitemid 32613012)
181. Vaquero A., Sternglanz R., Reinberg D.. NAD+-Dependent Deacetylation of H4 Lysine 16 by Class III HDACs. Oncogene. 2007 ; 26 (37). 5505-5520 (Pubitemid 47255931)
182. North B. J., Marshall B. L., Borra M. T., Denu J. M., Verdin E.. The Human Sir2 ortholog, SIRT2, Is an NAD+-Dependent Tubulin Deacetylase. Mol. Cell. 2003 ; 11 (2). 437-444 (Pubitemid 36293837)
183. Jin L., Wei W., Jiang Y., Peng H., Cai J., Mao C., Dai H., Choy W., Bemis J. E., Jirousek M. R., et al. Crystal Structures of Human SIRT3 Displaying Substrate-Induced Conformational Changes. J. Biol. Chem. 2009 ; 284 (36). 24394-24405
184. Scher M. B., Vaquero A., Reinberg D.. SirT3 Is a Nuclear NAD+-Dependent Histone Deacetylase That Translocates to the Mitochondria upon Cellular Stress. Genes Dev. 2007 ; 21 (8). 920-928 (Pubitemid 46625641)
185. Sundaresan N. R., Samant S. A., Pillai V. B., Rajamohan S. B., Gupta M. P.. SIRT3 Is a Stress-Responsive Deacetylase in Cardiomyocytes That Protects Cells from Stress-Mediated Cell Death by Deacetylation of Ku70. Mol. Cell. Biol. 2008 ; 28 (20). 6384-6401
186. Someya S., Yu W., Hallows W. C., Xu J., Vann J. M., Leeuwenburgh C., Tanokura M., Denu J. M., Prolla T. A.. Sirt3 Mediates Reduction of Oxidative Damage and Prevention of Age-Related Hearing Loss under Caloric Restriction. Cell. 2010 ; 143 (5). 802-812
187. Schlicker C., Gertz M., Papatheodorou P., Kachholz B., Becker C. F., Steegborn C.. Substrates and Regulation Mechanisms for the Human Mitochondrial Sirtuins Sirt3 and Sirt5. J. Mol. Biol. 2008 ; 382 (3). 790-801
188. Shimazu T., Hirschey M. D., Hua L., Dittenhafer-Reed K. E., Schwer B., Lombard D. B., Li Y., Bunkenborg J., Alt F. W., Denu J. M., Jacobson M. P., et al. SIRT3 Deacetylates Mitochondrial 3-Hydroxy-3-Methylglutaryl CoA Synthase 2 and Regulates Ketone Body Production. Cell Metab. 2010 ; 12 (6). 654-661
189. Schwer B., Bunkenborg J., Verdin R. O., Andersen J. S., Verdin E.. Reversible Lysine Acetylation Controls the Activity of the Mitochondrial Enzyme Acetyl-CoA Synthetase 2. Proc. Natl. Acad. Sci. U. S. A. 2006 ; 103 (27). 10224-10229 (Pubitemid 44051148)
190. Cimen H., Han M. J., Yang Y., Tong Q., Koc H., Koc E. C.. Regulation of Succinate Dehydrogenase Activity by SIRT3 in Mammalian Mitochondria. Biochemistry. 2010 ; 49 (2). 304-311
191. Chen Y., Zhang J., Lin Y., Lei Q., Guan K. L., Zhao S., Xiong Y.. Tumour Suppressor SIRT3 Deacetylates and Activates Manganese Superoxide Dismutase to Scavenge ROS. EMBO Rep. 2011 ; 12 (6). 534-541
192. Qiu X., Brown K., Hirschey M. D., Verdin E., Chen D.. Calorie Restriction Reduces Oxidative Stress by SIRT3-Mediated SOD2 Activation. Cell. Metab. 2010 ; 12 (6). 662-667
193. Hirschey M. D., Shimazu T., Goetzman E., Jing E., Schwer B., Lombard D. B., Grueter C. A., Harris C., Biddinger S., Ilkayeva O. R., et al. SIRT3 Regulates Mitochondrial Fatty-Acid Oxidation by Reversible Enzyme Deacetylation. Nature. 2010 ; 464 (7285). 121-125
194. Lombard D. B., Alt F. W., Cheng H. L., Bunkenborg J., Streeper R. S., Mostoslavsky R., Kim J., Yancopoulos G., Valenzuela D., Murphy A., et al. Mammalian Sir2 Homolog SIRT3 Regulates Global Mitochondrial Lysine Acetylation. Mol. Cell. Biol. 2007 ; 27 (24). 8807-8814
195. Ahn B. H., Kim H. S., Song S., Lee I. H., Liu J., Vassilopoulos A., Deng C. X., Finkel T.. A Role for the Mitochondrial Deacetylase Sirt3 in Regulating Energy Homeostasis. Proc. Natl. Acad. Sci. U. S. A. 2008 ; 105 (38). 14447-14452
196. Haigis M. C., Mostoslavsky R., Haigis K. M., Fahie K., Christodoulou D. C., Murphy A. J., Valenzuela D. M., Yancopoulos G. D., Karow M., Blander G., et al. SIRT4 Inhibits Glutamate Dehydrogenase and Opposes the Effects of Calorie Restriction in Pancreatic Beta Cells. Cell. 2006 ; 126 (5). 941-954 (Pubitemid 44321935)
197. Nasrin N., Wu X., Fortier E., Feng Y., Bare O. C., Chen S., Ren X., Wu Z., Streeper R. S., Bordone L.. SIRT4 Regulates Fatty Acid Oxidation and Mitochondrial Gene Expression in Liver and Muscle Cells. J. Biol. Chem. 2010 ; 285 (42). 31995-32002
198. Schuetz A., Min J., Antoshenko T., Wang C. L., Allali-Hassani A., Dong A., Loppnau P., Bochkarev A., Sternglanz R., Plotnikov A. N.. Structural Basis of Inhibition of the Human NAD+-Dependent Deacetylase SIRT5 by Suramin. Structure. 2007 ; 15 (3). 377-389 (Pubitemid 46366726)
199. Nakagawa T., Lomb D. J., Haigis M. C., Guarente L.. SIRT5 Deacetylates Carbamoyl Phosphate Synthetase 1 and Regulates the Urea Cycle. Cell. 2009 ; 137 (3). 560-570
200. Kawahara T. L., Michishita E., Adler A. S., Damian M., Berber E., Lin M., McCord R. A., Ongaigui K. C., Boxer L. D., Chang H. Y., et al. SIRT6 Links Histone H3 Lysine 9 Deacetylation to NF-kappaB-Dependent Gene Expression and Organismal Life Span. Cell. 2009 ; 136 (1). 62-74
201. Michishita E., McCord R. A., Berber E., Kioi M., Padilla-Nash H., Damian M., Cheung P., Kusumoto R., Kawahara T. L., Barrett J. C., et al. SIRT6 Is a Histone H3 Lysine 9 Deacetylase That Modulates Telomeric Chromatin. Nature. 2008 ; 452 (7186). 492-496 (Pubitemid 351450840)
202. Michishita E., McCord R. A., Boxer L. D., Barber M. F., Hong T., Gozani O., Chua K. F.. Cell Cycle-Dependent Deacetylation of Telomeric Histone H3 Lysine K56 by Human SIRT6. Cell Cycle. 2009 ; 8 (16). 2664-2666
203. Mostoslavsky R., Chua K. F., Lombard D. B., Pang W. W., Fischer M. R., Gellon L, Liu P, Mostoslavsky G., Franco S., Murphy M. M., et al. Genomic Instability and Aging-Like Phenotype in the Absence of Mammalian SIRT6. Cell. 2006 ; 124 (2). 315-329 (Pubitemid 43121980)
204. Ford E., Voit R., Liszt G., Magin C., Grummt I., Guarente L.. Mammalian Sir2 Homolog SIRT7 Is an Activator of RNA Polymerase I Transcription. Genes Dev. 2006 ; 20 (9). 1075-1080
205. Schmidt M. T., Smith B. C., Jackson M. D., Denu J. M.. Coenzyme Specificity of Sir2 Protein Deacetylases: Implications for Physiological Regulation. J. Biol. Chem. 2004 ; 279 (38). 40122-40129 (Pubitemid 39258287)
206. Neugebauer R. C., Uchiechowska U., Meier R., Hruby H., Valkov V., Verdin E., Sippl W., Jung M.. Structure-Activity Studies on Splitomicin Derivatives as Sirtuin Inhibitors and Computational Prediction of Binding Mode. J. Med. Chem. 2008 ; 51 (5). 1203-1213 (Pubitemid 351480382)
207. Rotili D., Tarantino D., Carafa V., Lara E., Meade S., Botta G., Nebbioso A., Schemies J., Jung M., Kazantsev A. G., et al. Identification of Tri- and Tetracyclic Pyrimidinediones as Sirtuin Inhibitors. Chem MedChem. 2010 ; 5 (5). 674-677
208. Posakony J., Hirao M., Stevens S., Simon J. A., Bedalov A.. Inhibitors of Sir2: Evaluation of Splitomicin Analogues. J. Med. Chem. 2004 ; 47 (10). 2635-2644 (Pubitemid 38580099)
209. Mai A., Massa S., Lavu S., Pezzi R., Simeoni S., Ragno R., Mariotti F. R., Chiani F., Camilloni G., Sinclair D. A.. Design, Synthesis, and Biological Evaluation of Sirtinol Analogues as Class III Histone/Protein Deacetylase (Sirtuin) Inhibitors. J. Med. Chem. 2005 ; 48 (24). 7789-7795 (Pubitemid 41698818)