Abstract
The sirtuins are a protein family named after the first identified member, S. cerevisiae Sir2p. Sirtuins are protein deacetylases whose activity is dependent on NAD+ as a cosubstrate. They are structurally defined by two central domains that together form a highly conserved catalytic center, which catalyzes the transfer of an acetyl moiety from acetyllysine to NAD+, yielding nicotinamide, the unique metabolite O-acetyl-ADP-ribose and deacetylated lysine. One or more sirtuins are present in virtually all species from bacteria to mammals. Here we describe a phylogenetic analysis of sirtuins. Based on their phylogenetic relationship, sirtuins can be grouped into over a dozen classes and subclasses. Humans, like most vertebrates, have seven sirtuins: SIRT1-SIRT7. These function in diverse cellular pathways, regulating transcriptional repression, aging, metabolism, DNA damage responses and apoptosis. We show that these seven sirtuins arose early during animal evolution. Conserved residues cluster around the catalytic center of known sirtuin family members.
Similar content being viewed by others
References
Ahuja, N., Schwer, B., Carobbio, S., Waltregny, D., North, B.J., Castronovo, V., Maechler, P., and Verdin, E. (2007). Regulation of insulin secretion by SIRT4, a mitochondrial ADP-ribosyltransferase. J. Biol. Chem. 282, 33583–33592.
Aparicio, O.M., Billington, B.L., and Gottschling, D.E. (1991). Modifiers of position effect are shared between telomeric and silent mating-type loci in S. cerevisiae. Cell 66, 1279–1287.
Astrom, S.U., Cline, T.W., and Rine, J. (2003). The Drosophila melanogaster sir2+ gene is nonessential and has only minor effects on position-effect variegation. Genetics 163, 931–937.
Avalos, J.L., Celic, I., Muhammad, S., Cosgrove, M.S., Boeke, J.D., and Wolberger, C. (2002). Structure of a Sir2 enzyme bound to an acetylated p53 peptide. Mol. Cell 10, 523–535.
Baldauf, S.L. (2003). The deep roots of eukaryotes. Science 300, 1703–1706.
Blander, G., Olejnik, J., Krzymanska-Olejnik, E., McDonagh, T., Haigis, M., Yaffe, M.B., and Guarente, L. (2005). SIRT1 shows no substrate specificity in vitro. J. Biol. Chem. 280, 9780–9785.
Bowler, C., Allen, A.E., Badger, J.H., Grimwood, J., Jabbari, K., Kuo, A., Maheswari, U., Martens, C., Maumus, F., Otillar, R.P., et al. (2008). The Phaeodactylum genome reveals the evolutionary history of diatom genomes. Nature 456, 239–244.
Braunstein, M., Rose, A.B., Holmes, S.G., Allis, C.D., and Broach, J.R. (1993). Transcriptional silencing in yeast is associated with reduced nucleosome acetylation. Genes Dev. 7, 592–604.
Braunstein, M., Sobel, R.E., Allis, C.D., Turner, B.M., and Broach, J.R. (1996). Efficient transcriptional silencing in Saccharomyces cerevisiae requires a heterochromatin histone acetylation pattern. Mol. Cell Biol. 16, 4349–4356.
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. (2004). Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase. Science 303, 2011–2015.
Bryk, M., Banerjee, M., Murphy, M., Knudsen, K.E., Garfinkel, D.J., and Curcio, M.J. (1997). Transcriptional silencing of Ty1 elements in the RDN1 locus of yeast. Genes Dev. 11, 255–269.
Chang, J.H., Kim, H.C., Hwang, K.Y., Lee, J.W., Jackson, S.P., Bell, S.D., and Cho, Y. (2002). Structural basis for the NAD-dependent deacetylase mechanism of Sir2. J. Biol. Chem. 277, 34489–34498.
Cohen, H.Y., Miller, C., Bitterman, K.J., Wall, N.R., Hekking, B., Kessler, B., Howitz, K.T., Gorospe, M., de Cabo, R., and Sinclair, D.A. (2004). Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase. Science 305, 390–392.
Dai, J.M., Wang, Z.Y., Sun, D.C., Lin, R.X., and Wang, S.Q. (2007). SIRT1 interacts with p73 and suppresses p73-dependent transcriptional activity. J. Cell Physiol. 210, 161–166.
Dali-Youcef, N., Lagouge, M., Froelich, S., Koehl, C., Schoonjans, K., and Auwerx, J. (2007). Sirtuins: the ‘magnificent seven”, function, metabolism and longevity. Ann. Med. 39, 335–345.
Der Ou, H.D., Lohr, F., Vogel, V., Mantele, W., and Dotsch, V. (2007). Structural evolution of C-terminal domains in the p53 family. EMBO J. 26, 3463–3473.
Du, J., Jiang, H., and Lin, H. (2009). Investigating the ADPribosyltransferase activity of sirtuins with NAD analogs and 32PNAD. Biochemistry 48, 2878–2890.
Dryden, S.C., Nahhas, F.A., Nowak, J.E., Goustin, A.S., and Tainsky, M.A. (2003). Role for human SIRT2 NAD-dependent deacetylase activity in control of mitotic exit in the cell cycle. Mol. Cell Biol. 23, 3173–3185.
Eichinger, L., Pachebat, J.A., Glockner, G., Rajandream, M.A., Sucgang, R., Berriman, M., Song, J., Olsen, R., Szafranski, K., Xu, Q., et al. (2005). The genome of the social amoeba Dictyostelium discoideum. Nature 435, 43–57.
Finnin, M.S., Donigian, J.R., and Pavletich, N.P. (2001). Structure of the histone deacetylase SIRT2. Nat. Struct. Biol. 8, 621–625.
Ford, E., Voit, R., Liszt, G., Magin, C., Grummt, I., and Guarente, L. (2006). Mammalian Sir2 homolog SIRT7 is an activator of RNA polymerase I transcription. Genes Dev. 20, 1075–1080.
Fritze, C.E., Verschueren, K., Strich, R., and Easton, E.R. (1997). Direct evidence for SIR2 modulation of chromatin structure in yeast rDNA. EMBO J. 16, 6495–6509.
Frye, R.A. (2000). Phylogenetic classification of prokaryotic and eukaryotic Sir2-like proteins. Biochem. Biophys. Res. Commun. 273, 793–798.
Gardner, M.J., Hall, N., Fung, E., White, O., Berriman, M., Hyman, R.W., Carlton, J.M., Pain, A., Nelson, K.E., Bowman, S., et al. (2002). Genome sequence of the human malaria parasite Plasmodium falciparum. Nature 419, 498–511.
Ghedin, E., Wang, S., Spiro, D., Caler, E., Zhao, Q., Crabtree, J., Allen, J.E., Delcher, A.L., Guiliano, D.B., Miranda-Saavedra, D., et al. (2007). Draft genome of the filarial nematode parasite Brugia malayi. Science 317, 1756–1760.
Gottlieb, S., and Esposito, R.E. (1989). A new role for a yeast transcriptional silencer gene, SIR2, in regulation of recombination in ribosomal DNA. Cell 56, 771–776.
Greiss, S., Hall, J., Ahmed, S., and Gartner, A. (2008). C. elegans SIR-2.1 translocation is linked to a proapoptotic pathway parallel to cep-1/p53 during DNA damage-induced apoptosis. Genes Dev. 22, 2831–2842.
Haigis, M.C., and Guarente, L.P. (2006). Mammalian sirtuins — emerging roles in physiology, aging, and calorie restriction. Genes Dev. 20, 2913–2921.
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. (2006). SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic beta cells. Cell 126, 941–954.
Hallows, W.C., Lee, S., and Denu, J.M. (2006). Sirtuins deacetylate and activate mammalian acetyl-CoA synthetases. Proc. Natl. Acad. Sci. USA 103, 10230–10235.
Hiratsuka, M., Inoue, T., Toda, T., Kimura, N., Shirayoshi, Y., Kamitani, H., Watanabe, T., Ohama, E., Tahimic, C.G., Kurimasa, A., et al. (2003). Proteomics-based identification of differentially expressed genes in human gliomas: down-regulation of SIRT2 gene. Biochem. Biophys. Res. Commun. 309, 558–566.
Holbert, M.A., and Marmorstein, R. (2005). Structure and activity of enzymes that remove histone modifications. Curr. Opin. Struct. Biol. 15, 673–680.
Hu, P., Wang, S., and Zhang, Y. (2008). Highly dissociative and concerted mechanism for the nicotinamide cleavage reaction in Sir2Tm enzyme suggested by Ab Initio QM/MM molecular dynamics simulations. J. Am. Chem. Soc. 130, 16721–16728.
Huson, D.H., and Bryant, D. (2006). Application of phylogenetic networks in evolutionary studies. Mol. Biol. Evol. 23, 254–267.
Imai, S., Armstrong, C.M., Kaeberlein, M., and Guarente, L. (2000). Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Nature 403, 795–800.
Inoue, T., Hiratsuka, M., Osaki, M., Yamada, H., Kishimoto, I., Yamaguchi, S., Nakano, S., Katoh, M., Ito, H., and Oshimura, M. (2006). SIRT2, a tubulin deacetylase, acts to block the entry to chromosome condensation in response to mitotic stress. Oncogene 26, 945–957.
Ivy, J.M., Hicks, J.B., and Klar, A.J. (1985). Map positions of yeast genes SIR1, SIR3 and SIR4. Genetics 111, 735–744.
Ivy, J.M., Klar, A.J., and Hicks, J.B. (1986). Cloning and characterization of four SIR genes of Saccharomyces cerevisiae. Mol. Cell. Biol. 6, 688–702.
Jin, Q., Yan, T., Ge, X., Sun, C., Shi, X., and Zhai, Q. (2007). Cytoplasm-localized SIRT1 enhances apoptosis. J. Cell Physiol. 213, 88–97.
Kaeberlein, M., McVey, M., and Guarente, L. (1999). The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms. Genes Dev. 13, 2570–2580.
Katinka, M.D., Duprat, S., Cornillot, E., Metenier, G., Thomarat, F., Prensier, G., Barbe, V., Peyretaillade, E., Brottier, P., Wincker, P., et al. (2001). Genome sequence and gene compaction of the eukaryote parasite Encephalitozoon cuniculi. Nature 414, 450–453.
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. (2009). SIRT6 links histone H3 lysine 9 deacetylation to NF-kappaB-dependent gene expression and organismal life span. Cell 136, 62–74.
Khan, A.N., and Lewis, P.N. (2005). Unstructured conformations are a substrate requirement for the Sir2 family of NADdependent protein deacetylases. J. Biol. Chem. 280, 36073–36078.
King, N., Westbrook, M.J., Young, S.L., Kuo, A., Abedin, M., Chapman, J., Fairclough, S., Hellsten, U., Isogai, Y., Letunic, I., et al. (2008). The genome of the choanoflagellate Monosiga brevicollis and the origin of metazoans. Nature 451, 783–788.
Klar, A.J., Fogel, S., and Macleod, K. (1979). MAR1 — a Regulator of the HMa and HMα Loci in Saccharomyces cerevisiae. Genetics 93, 37–50.
Kowieski, T.M., Lee, S., and Denu, J.M. (2008). Acetylationdependent ADP-ribosylation by Trypanosoma brucei Sir2. J. Biol. Chem. 283, 5317–5326.
Landry, J., Sutton, A., Tafrov, S.T., Heller, R.C., Stebbins, J., Pillus, L., and Sternglanz, R. (2000). The silencing protein SIR2 and its homologs are NAD-dependent protein deacetylases. Proc. Natl. Acad. Sci. USA 97, 5807–5811.
Liszt, G., Ford, E., Kurtev, M., and Guarente, L. (2005). Mouse Sir2 homolog SIRT6 is a nuclear ADP-ribosyltransferase. J. Biol. Chem. 280, 21313–21320.
Lombard, D.B., Schwer, B., Alt, F.W., and Mostoslavsky, R. (2008). SIRT6 in DNA repair, metabolism and ageing. J. Intern. Med. 263, 128–141.
Longo, V.D., and Kennedy, B.K. (2006). Sirtuins in aging and agerelated disease. Cell 126, 257–268.
Luo, J., Nikolaev, A.Y., Imai, S., Chen, D., Su, F., Shiloh, A., Guarente, L., and Gu, W. (2001). Negative control of p53 by Sir2alpha promotes cell survival under stress. Cell 107, 137–148.
Mead, J., McCord, R., Youngster, L., Sharma, M., Gartenberg, M.R., and Vershon, A.K. (2007). Swapping the gene-specific and regional silencing specificities of the Hst1 and Sir2 histone deacetylases. Mol. Cell. Biol. 27, 2466–2475.
Meng, E.C., Pettersen, E.F., Couch, G.S., Huang, C.C., and Ferrin, T.E. (2006). Tools for integrated sequence-structure analysis with UCSF Chimera. BMC Bioinformatics 7, 339.
Michishita, E., Park, J.Y., Burneskis, J.M., Barrett, J.C., and Horikawa, I. (2005). Evolutionarily conserved and nonconserved cellular localizations and functions of human SIRT proteins. Mol. Biol. Cell 16, 4623–4635.
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. (2008). SIRT6 is a histone H3 lysine 9 deacetylase that modulates telomeric chromatin. Nature 452, 492–496.
Min, J., Landry, J., Sternglanz, R., and Xu, R.M. (2001). Crystal structure of a SIR2 homolog-NAD complex. Cell 105, 269–279.
Motta, M.C., Divecha, N., Lemieux, M., Kamel, C., Chen, D., Gu, W., Bultsma, Y., McBurney, M., and Guarente, L. (2004). Mammalian SIRT1 represses forkhead transcription factors. Cell 116, 551–563.
Newman, B.L., Lundblad, J.R., Chen, Y., and Smolik, S.M. (2002). A Drosophila homologue of Sir2 modifies position-effect variegation but does not affect life span. Genetics 162, 1675–1685.
North, B.J., and Verdin, E. (2004). Sirtuins: Sir2-related NADdependent protein deacetylases. Genome Biol. 5, 224.
Oberdoerffer, P., Michan, S., McVay, M., Mostoslavsky, R., Vann, J., Park, S.K., Hartlerode, A., Stegmuller, J., Hafner, A., Loerch, P., et al. (2008). SIRT1 redistribution on chromatin promotes genomic stability but alters gene expression during aging. Cell 135, 907–918.
Pankow, S., and Bamberger, C. (2007). The p53 tumor suppressorlike protein nvp63 mediates selective germ cell death in the sea anemone Nematostella vectensis. PLoS ONE 2, e782.
Pettersen, E.F., Goddard, T.D., Huang, C.C., Couch, G.S., Greenblatt, D.M., Meng, E.C., and Ferrin, T.E. (2004). UCSF Chimera — a visualization system for exploratory research and analysis. J. Comput. Chem. 25, 1605–1612.
Picard, F., Kurtev, M., Chung, N., Topark-Ngarm, A., Senawong, T., Machado, D.O., Leid, M., McBurney, M.W., and Guarente, L. (2004). Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-gamma. Nature 429, 771–776.
Potente, M., Ghaeni, L., Baldessari, D., Mostoslavsky, R., Rossig, L., Dequiedt, F., Haendeler, J., Mione, M., Dejana, E., Alt, F.W., et al. (2007). SIRT1 controls endothelial angiogenic functions during vascular growth. Genes Dev. 21, 2644–2658.
Pruitt, K., Zinn, R.L., Ohm, J.E., McGarvey, K.M., Kang, S.H., Watkins, D.N., Herman, J.G., and Baylin, S.B. (2006). Inhibition of SIRT1 reactivates silenced cancer genes without loss of promoter DNA hypermethylation. PLoS Genet. 2, e40.
Rensing, S.A., Lang, D., Zimmer, A.D., Terry, A., Salamov, A., Shapiro, H., Nishiyama, T., Perroud, P.F., Lindquist, E.A., Kamisugi, Y., et al. (2008). The Physcomitrella genome reveals evolutionary insights into the conquest of land by plants. Science 319, 64–69.
Richards, S., Gibbs, R.A., Weinstock, G.M., Brown, S.J., Denell, R., Beeman, R.W., Gibbs, R., Bucher, G., Friedrich, M., Grimmelikhuijzen, C.J., et al. (2008). The genome of the model beetle and pest Tribolium castaneum. Nature 452, 949–955.
Rodgers, J.T., Lerin, C., Haas, W., Gygi, S.P., Spiegelman, B.M., and Puigserver, P. (2005). Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1. Nature 434, 113–118.
Rogina, B., and Helfand, S.L. (2004). Sir2 mediates longevity in the fly through a pathway related to calorie restriction. Proc. Natl. Acad. Sci. USA 101, 15998–16003.
Rosenberg, M.I., and Parkhurst, S.M. (2002). Drosophila Sir2 is required for heterochromatic silencing and by euchromatic Hairy/E(Spl). bHLH repressors in segmentation and sex determination. Cell 109, 447–458.
Sauve, A.A., Celic, I., Avalos, J., Deng, H., Boeke, J.D., and Schramm, V.L. (2001). Chemistry of gene silencing: the mechanism of NAD+-dependent deacetylation reactions. Biochemistry 40, 15456–15463.
Schlicker, C., Gertz, M., Papatheodorou, P., Kachholz, B., Becker, C.F., and Steegborn, C. (2008). Substrates and regulation mechanisms for the human mitochondrial sirtuins Sirt3 and Sirt5. J. Mol. Biol. 382, 790–801.
Schwer, B., and Verdin, E. (2008). Conserved metabolic regulatory functions of sirtuins. Cell Metab. 7, 104–112.
Schwer, B., Bunkenborg, J., Verdin, R.O., Andersen, J.S., and Verdin, E. (2006). Reversible lysine acetylation controls the activity of the mitochondrial enzyme acetyl-CoA synthetase 2. Proc. Natl. Acad. Sci. USA 103, 10224–10229.
Shou, W., Seol, J.H., Shevchenko, A., Baskerville, C., Moazed, D., Chen, Z.W., Jang, J., Shevchenko, A., Charbonneau, H., and Deshaies, R.J. (1999). Exit from mitosis is triggered by Tem1-dependent release of the protein phosphatase Cdc14 from nucleolar RENT complex. Cell 97, 233–244.
Sinclair, D.A., and Guarente, L. (1997). Extrachromosomal rDNA circles — a cause of aging in yeast. Cell 91, 1033–1042.
Smith, J.S., Brachmann, C.B., Celic, I., Kenna, M.A., Muhammad, S., Starai, V.J., Avalos, J.L., Escalante-Semerena, J.C., Grubmeyer, C., Wolberger, C., et al. (2000). A phylogenetically conserved NAD+-dependent protein deacetylase activity in the Sir2 protein family. Proc. Natl. Acad. Sci USA 97, 6658–6663.
Solignac, M., Zhang, L., Mougel, F., Li, B., Vautrin, D., Monnerot, M., Cornuet, J. M., Worley, K.C., Weinstock, G.M., and Gibbs, R.A. (2007). The genome of Apis mellifera: dialog between linkage mapping and sequence assembly. Genome Biol. 8, 403.
Srivastava, M., Begovic, E., Chapman, J., Putnam, N.H., Hellsten, U., Kawashima, T., Kuo, A., Mitros, T., Salamov, A., Carpenter, M.L., et al. (2008). The Trichoplax genome and the nature of placozoans. Nature 454, 955–960.
Stein, L.D., Bao, Z., Blasiar, D., Blumenthal, T., Brent, M.R., Chen, N., Chinwalla, A., Clarke, L., Clee, C., Coghlan, A., et al. (2003). The genome sequence of Caenorhabditis briggsae: a platform for comparative genomics. PLoS Biol. 1, E45.
Straight, A.F., Shou, W., Dowd, G.J., Turck, C.W., Deshaies, R.J., Johnson, A.D., and Moazed, D. (1999). Net1, a Sir2-associated nucleolar protein required for rDNA silencing and nucleolar integrity. Cell 97, 245–256.
Tanner, K.G., Landry, J., Sternglanz, R., and Denu, J.M. (2000). Silent information regulator 2 family of NAD-dependent histone/protein deacetylases generates a unique product, 1-Oacetyl-ADP-ribose. Proc. Natl. Acad. Sci. USA 97, 14178–14182.
Tanno, M., Sakamoto, J., Miura, T., Shimamoto, K., and Horio, Y. (2007). Nucleocytoplasmic shuttling of the NAD+-dependent histone deacetylase SIRT1. J. Biol. Chem. 282, 6823–6832.
Tanny, J.C., and Moazed, D. (2001). Coupling of histone deacetylation to NAD breakdown by the yeast silencing protein Sir2: Evidence for acetyl transfer from substrate to an NAD breakdown product. Proc. Natl. Acad. Sci. USA 98, 415–420.
Tanny, J.C., Dowd, G.J., Huang, J., Hilz, H., and Moazed, D. (1999). An enzymatic activity in the yeast Sir2 protein that is essential for gene silencing. Cell 99, 735–745.
Tissenbaum, H.A., and Guarente, L. (2001). Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans. Nature 410, 227–230.
Tsang, A.W., and Escalante-Semerena, J.C. (1998). CobB, a new member of the SIR2 family of eucaryotic regulatory proteins, is required to compensate for the lack of nicotinate mononucleotide: 5,6-dimethylbenzimidazole phosphoribosyltransferase activity in cobT mutants during cobalamin biosynthesis in Salmonella typhimurium LT2. J. Biol. Chem. 273, 31788–31794.
van der Horst, A., Tertoolen, L.G., Vries-Smits, L.M., Frye, R.A., Medema, R.H., and Burgering, B.M. (2004). FOXO4 is acetylated upon peroxide stress and deacetylated by the longevity protein hSir2SIRT1. J. Biol. Chem. 279, 28873–28879.
Vaquero, A., Scher, M., Lee, D., Erdjument-Bromage, H., Tempst, P., and Reinberg, D. (2004). Human SirT1 interacts with histone H1 and promotes formation of facultative heterochromatin. Mol. Cell 16, 93–105.
Vaquero, A., Scher, M.B., Lee, D.H., Sutton, A., Cheng, H.L., Alt, F.W., Serrano, L., Sternglanz, R., and Reinberg, D. (2006). SirT2 is a histone deacetylase with preference for histone H4 Lys 16 during mitosis. Genes Dev. 20, 1256–1261.
Vaquero, A., Scher, M., Erdjument-Bromage, H., Tempst, P., Serrano, L., and Reinberg, D. (2007). SIRT1 regulates the histone methyltransferase SUV39H1 during heterochromatin formation. Nature 450, 440–444.
Vaziri, H., Dessain, S.K., Ng, E.E., Imai, S.I., Frye, R.A., Pandita, T.K., Guarente, L., and Weinberg, R.A. (2001). hSIR2(SIRT1). functions as an NAD-dependent p53 deacetylase. Cell 107, 149–159.
Wang, C., Chen, L., Hou, X., Li, Z., Kabra, N., Ma, Y., Nemoto, S., Finkel, T., Gu, W., Cress, W.D., et al. (2006). Interactions between E2F1 and SirT1 regulate apoptotic response to DNA damage. Nat. Cell Biol. 8, 1025–1031.
Waterhouse, A.M., Procter, J.B., Martin, D.M., Clamp, M., and Barton, G.J. (2009). Jalview Version 2 — a multiple sequence alignment editor and analysis workbench. Bioinformatics 25, 1189–1191.
Wood, J.G., Rogina, B., Lavu, S., Howitz, K., Helfand, S.L., Tatar, M., and Sinclair, D. (2004). Sirtuin activators mimic caloric restriction and delay ageing in metazoans. Nature 430, 686–689.
Yamamoto, H., Schoonjans, K., and Auwerx, J. (2007). Sirtuin functions in health and disease. Mol. Endocrinol. 21, 1745–1755.
Yeung, F., Hoberg, J.E., Ramsey, C.S., Keller, M.D., Jones, D.R., Frye, R.A., and Mayo, M.W. (2004). Modulation of NF-kappaBdependent transcription and cell survival by the SIRT1 deacetylase. EMBO J. 23, 2369–2380.
Zhao, K., Chai, X., Clements, A., and Marmorstein, R. (2003a). Structure and autoregulation of the yeast Hst2 homolog of Sir2. Nat. Struct. Biol. 10, 864–871.
Zhao, K., Chai, X., and Marmorstein, R. (2003b). Structure of the yeast Hst2 protein deacetylase in ternary complex with 2′-Oacetyl ADP ribose and histone peptide. Structure 11, 1403–1411.
Zhao, K., Harshaw, R., Chai, X., and Marmorstein, R. (2004). Structural basis for nicotinamide cleavage and ADP-ribose transfer by NAD+-dependent Sir2 histone/protein deacetylases. Proc. Natl. Acad. Sci. USA 101, 8563–8568.
Author information
Authors and Affiliations
Corresponding author
About this article
Cite this article
Greiss, S., Gartner, A. Sirtuin/Sir2 phylogeny, evolutionary considerations and structural conservation. Mol Cells 28, 407–415 (2009). https://doi.org/10.1007/s10059-009-0169-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10059-009-0169-x