Sirtuin Genes and Functions

Abstract

Many studies have been conducted on the potential role, on several diseases, of 23 Sirtuin (SIRT) family genes known as NAD + dependent class III deacetylase enzymes. Regarding the published literature, Sirtuins have been thought to play a significant role on the treatment of diabetes type II, obesity, cancer, aging, and several neuro-degenerative diseases. As a result of recent studies, in order to be able to study the role of SIRT genes on biological systems, which is providing positive results for the treatment of many diseases, it is important to understand the molecular and chemical structure of them.

Keywords

• Sirtuin, SIRT, Human Health, Regulation of Gene Expression, Cancer.

Sirtuin Genleri ve İşlevleri

Öz

NAD + bağımlı sınıf III deasetilaz enzimler olarak bilinen Sirtuin (SIRT) ailesi genleri ile ilgili olarak çeşitli hastalıklardaki potansiyel rolü üzerine birçok çalışma yapılmıştır. Yayımlanmış literatüre dayanarak Sirtuinlerin; tip II diyabet, obezite, kanser, yaşlanma ve çeşitli nörodejeneratif hastalıkların tedavisinde önemli rol oynadığı düşünülmektedir. Son yapılan çalışmalar sonucu birçok sağlık probleminin tedavisine yönelik olumlu sonuçlar veren SIRT genlerinin biyolojik sistemlerdeki rolünü çalışabilmek için moleküler ve kimyasal yapısını anlamak çok önemlidir.

Anahtar Kelimeler

• Sirtuin, SIRT, İnsan Sağlığı, Gen İfadesinin Düzenlenmesi, Kanser.

Kaynakça

1. Bitterman KJ, Anderson RM, Cohen HY, Latorre-Esteves M, Sinclair DA. Inhibition of silencing and accelerated aging by nicotinamide, a putative negative regulator of yeast sir2 and human SIRT1. J Biol Chem 2002; 277: 45099-107.
2. Klar AJ, Fogel S, Macleod K. MAR1-a Regulator of the HMa and HMalpha Loci in Saccharomyces cerevisiase. Genetics 1979; 93: 37-50.
3. Michan S, Sinclair D. Sirtuins in mammals: insights into their biological function. Biochem J 2007; 404: 1-13.
4. North BJ, Marshall BL, Borra MT, Denu JM, Verdin E. The human Sir2 ortholog, SIRT2, is an NAD+-dependent tubulin deacetylase. Mol Cell 2003; 11: 437-44.
5. Haigis MC, Mostoslavsky R, Haigis KM, et al. SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic beta cells. Cell 2006; 126: 941-54.
6. Shi T, Wang F, Stieren E, Tong Q. SIRT3, a mitochondrial sirtuin deacetylase, regulates mitochondrial function and thermogenesis in brown adipocytes. J Biol Chem 2005; 280: 13560Glozak AM, Sengupta N, Zhang X, Seto E. Acetylation and deacetylation of non-histone proteins. Gene 2005; 363: 15-23.
7. Taddei A, Roche D, Bickmore WA, Almouzni G. The effects of histone deacetylase inhibitors on heterochromation: implications for anti-cancer therapy? EMBO Reports 2005; 6: 520
8. Gray GS, Ekström JT, The human histone deacetylase family. Exp Cell Res 2001; 262: 75-83.

9. Bae NS, Swanson MJ, Vassilev A, Howard BH. Human histone deacetylase SIRT2 interacts with the homeobox transcription factor HOXA10. J Biochem 2004; 135: 695-700.
10. Chen WY, Wang DH, Yen RC, Luo J, Gu W, Baylin SB. Tumor suppressor HIC1 directly regulates SIRT1 to modulate p53-dependent DNA-damage responses. Cell 2005; 123: 437
11. 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: 1353-62.
12. Bouras T, Fu M, Sauve AA, et al. SIRT1 deacetylation and repression of p300 involves lysine residues 1020/1024 within the cell cycle regulatory domain 1. J Biol Chem 2005; 280: 10264-76.
13. Ashraf N, Zino S, Macintyre A, Kingsmore D, Payne AP, George WD, Shiels PG. Altered sirtuin expression is associated with node-positive breast cancer. Br J Cancer 2006; 95: 1056–61.
14. Vakhrusheva O, Smolka C, Gajawada P, et al. Sirt7 increases stress resistance of cardiomyocytes and prevents apoptosis and inflammatory cardiomyopathy in mice. Circ Res 2008; 102: 703 de Nigris F, Cerutti J, Morelli C, et al. Isolation of a SIR-like gene, SIR-T8, that is overexpressed in thyroid carcinoma cell lines and tissues. Br J Cancer 2002; 86: 917-23.
15. Yamamoto H, Schoonjans K, Auwerx J. Sirtuin functions in health and disease. Molecular endocrinology (Baltimore, Md). 2007; 218: 1745-55.
16. Zhang X, Gan L, Pan H, et al. Phosphorylation of serine 256 suppresses transactivation by FKHR (FOXO1) by multiple mechanisms. Direct and indirect effects on 78nuclear/cytoplasmic shuttling and DNA binding. J Biol Chem 2002; 277: 45276-84.
17. Brunet A, Sweeney LB, Sturgill JF, et al. Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase. Science 2004; 303: 2011-5.
18. Hiratsuka M, Inoue T, Toda T, et al. Proteomics-based identification of differentially expressed genes in human gliomas: down-regulation of SIRT2 gene. Biochem Biophys Res Commun 2003; 309: 558-66.
19. Vaziri H, Dessain SK, Ng Eaton E. hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase. Cell 2001; 107: 149
20. Vaziri H, Dessain SK, Ng Eaton E, et al. hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase. Cell 2001; 107: 149-59.
21. Beato M, Klug J. Steroid hormone receptors: an update. Hum Reprod Update 2000; 6: 225-36.
22. Evan G, Littlewood T. A matter of life and cell death. Science 1998; 281: 1317-21.
23. Toubi E, Shoenfeld Y. Protective autoimmunity in cancer. Oncol Rep 2007; 17: 245-51.
24. Saikumar P, Dong Z, Mikhailov V, Denton M, Weinberg JM, Venkatachalam MA. Apoptosis definition, mechanism and relevance to disease. Am J Med 1999; 107: 489-506.
25. Bayram A. MS hastalarında sırt genleri ve sırt genleri ile ilşkili genler ve gen ürünlerinin moleküler analizi. Gaziantep Üniversitesi Sağlık Bilimleri Enstitüsü Tıbbi Biyoloji Anabilim Dalı Doktora Tezi, 2013.
26. Chen WY, Wang DH, Yen RC, Luo J, Gu W, Baylin SB. Tumor suppressor HIC1 directly regulates SIRT1 to modulate p53-dependent DNA-damage responses. Cell 123: 437-48. Cohen HY, Miller C, Bitterman KJ, et al. Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase. Science 2004; 305: 390-2.
27. Wang C, Chen L, Hou X, et al. Interactions between E2F1 and SirT1 regulate apoptotic response to DNA damage. Nat Cell Biol 2006; 8: 1025-31.
28. Dai JM, Wang ZY, Sun DC, Lin RX, Wang SQ. SIRT1 interacts with p73 and suppresses p73-dependent transcriptional activity. J Cell Physiol 2007; 210: 161-6.
29. Ford J, Jiang M, Milner J. Cancer-specific functions of SIRT1 enable human epithelial cancer cell growth and survival. Cancer Res 2005; 65: 10457-63.
30. Langley E, Pearson M, Faretta M, et al. Human SIR2 deacetylates p53 and antagonizes PML/p53-induced cellular senescence. Embo J 2002; 21: 2383-96.
31. Mostoslavsky R, Chua KF, Lombard DB, et al. Genomic instability and aging-like phenotype in the absence of mammalian SIRT6. Cell 2006; 124: 315-29.
32. Kennedy BK, Austriaco NR, Jr Zhang J, Guarente L. Mutation in the silencing gene SIR4 can delay aging in S. cerevisiae. Cell 1995; 80: 485-96.
33. 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
34. Cheng HL, Mostoslavsky R, Saito S, et al. Developmental defects and p53 hyperacetylation in Sir2 homolog (SIRT1)deficient mice. Proc Natl Acad Sci USA 2003; 100: 10794-9.
35. Alcendor RR, Gao S, Zhai P, et al. Sirt1 regulates aging and resistance to oxidative stress in the heart. Circ Res 2007; 100: 1512Picard F, Kurtev M, Chung N, et al. Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-gamma. Nature 2004; 429: 771-6.
36. Sommer M, Poliak N, Upadhyay S, et al. DeltaNp63alpha overexpression induces downregulation of Sirt1 and an accelerated aging phenotype in the mouse. Cell Cycle 2006; 5: 2005
37. Baur JA, Pearson KJ, Price NL, et al. Resveratrol improves health and survival of mice on a high-calorie diet. Nature 2006; 444: 337-42.
38. Lemieux ME, Yang X, Jardine Ket, al. The Sirt1 deacetylase modulates the insulin-like growth factor signaling pathway in mammals. Mech Ageing Dev 2005; 126: 1097-105.
39. Jeong J, Juhn K, Lee H, et al. SIRT1 promotes DNA repair activity and deacetylation of Ku70. Exp Mol Med 2007; 39: 8
40. Yeung F, Hoberg JE, Ramsey CS, et al. Modulation of NFkappaB-dependent transcription and cell survival by the SIRT1 deacetylase. Embo J 2004; 23: 2369-80.
41. Nayagam VM, Wang X, Tan YC, et al. SIRT1 modulating compounds from high-throughput screening as antiinflammatory and insulin-sensitizing agents. J Biomol Screen 2006; 11: 959-67.
42. McBurney MW, Yang X, Jardine K, et al. The mammalian SIR2alpha protein has a role in embryogenesis and gametogenesis. Mol Cell Biol 2003; 23: 38-54.
43. Takata T, Ishikawa F. Human Sir2-related protein SIRT1 associates with the bHLH repressors HES1 and HEY2 and is involved in HES1- and HEY2-mediated transcriptional repression. Biochem Biophys Res Commun 2003; 301: 250-7.
44. Senawong T, Peterson VJ, Leid M. BCL11A-dependent recruitment of SIRT1 to a promoter template in mammalian cells results in histone deacetylation and transcriptional repression. Arch Biochem Biophys 2005; 434: 316-25.
45. Cohen HY, Miller C, Bitterman KJ, et al. Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase. Science 2004; 305: 390-2.
46. Frescas D, Valenti L, Accili D. Nuclear trapping of the forkhead transcription factor FoxO1 via Sirt-dependent deacetylation promotes expression of glucogenetic genes. J Biol Chem 2005; 280: 20589-95.
47. Rodgers JT, Lerin C, Haas W, Gygi SP, Spiegelman BM, Puigserver P. Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1. Nature 2005; 434: 113
48. Lagouge M, Argmann C, Gerhart-Hines Z, et al. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell 2006; 127: 1109-22.
49. Aslan K, Serdar Z, Tokullugil HA. Multifonksiyonel hormon: leptin. Uludağ Üniversitesi Tıp Fakültesi Dergisi, 2004; 30: 113
50. Arsenijevic D, Onuma H, Pecqueur C, et al. Disruption of the uncoupling protein-2 gene in mice reveals a role in immunity and reactive oxygen species production. Nat Genet 2000; 26: 435–
51. Donmez G, Wang D, Cohen DE, Guarente L. SIRT1 suppresses b-amyloid production by activating the a-secretase gene ADAM Cell 2010; 142: 320-32.