SIRT2

Summary

Gene Symbol: SIRT2
Description: sirtuin 2
Alias: SIR2, SIR2L, SIR2L2, NAD-dependent deacetylase sirtuin-2, NAD-dependent protein deacetylase sirtuin-2, SIR2-like protein 2, regulatory protein SIR2 homolog 2, silent information regulator 2, sir2-related protein type 2, sirtuin type 2
Species: human

Top Publications

  1. ncbi Modulation of sirtuins: new targets for antiageing
    Merce Pallas
    Unitat de Farmacologia i Farmacognòsia i Institut de Biomedicina IBUB, Facultat de Farmacia, Universitat de Barcelona, Nucli Universitari de Pedralbes, E 08028 Barcelona, Spain
    Recent Pat CNS Drug Discov 3:61-9. 2008
  2. ncbi The human Sir2 ortholog, SIRT2, is an NAD+-dependent tubulin deacetylase
    Brian J North
    Department of Physiology, University of California, San Francisco, 94141, San Francisco, CA, USA
    Mol Cell 11:437-44. 2003
  3. ncbi Proteomics-based identification of differentially expressed genes in human gliomas: down-regulation of SIRT2 gene
    Masaharu Hiratsuka
    Department of Molecular and Cell Genetics, Graduate School of Medical Science, Tottori University, Nishimachi 86, Yonago, Tottori 683 8503, Japan
    Biochem Biophys Res Commun 309:558-66. 2003
  4. pmc SIRT2 maintains genome integrity and suppresses tumorigenesis through regulating APC/C activity
    Hyun Seok Kim
    Genetics of Development and Disease Branch, 10 9N105, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Cancer Cell 20:487-99. 2011
  5. ncbi Human histone deacetylase SIRT2 interacts with the homeobox transcription factor HOXA10
    Nancy S Bae
    Laboratory of Molecular and Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    J Biochem 135:695-700. 2004
  6. ncbi Characterization of five human cDNAs with homology to the yeast SIR2 gene: Sir2-like proteins (sirtuins) metabolize NAD and may have protein ADP-ribosyltransferase activity
    R A Frye
    Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, 15240, USA
    Biochem Biophys Res Commun 260:273-9. 1999
  7. ncbi Multiple histone deacetylases and the CREB-binding protein regulate pre-mRNA 3'-end processing
    Tadahiro Shimazu
    Chemical Genetics Laboratory, Discovery Research Institute, RIKEN, Wako, Saitama 351 0198, Japan
    J Biol Chem 282:4470-8. 2007
  8. ncbi Characterization of a human gene with sequence homology to Saccharomyces cerevisiae SIR2
    G Afshar
    University of California, San Francisco, Radiation Oncology Research Laboratories, San Francisco, CA 94103, USA
    Gene 234:161-8. 1999
  9. doi Conserved metabolic regulatory functions of sirtuins
    Bjoern Schwer
    Gladstone Institute of Virology and Immunology, San Francisco, CA 94158, USA
    Cell Metab 7:104-12. 2008
  10. pmc Interphase nucleo-cytoplasmic shuttling and localization of SIRT2 during mitosis
    Brian J North
    Gladstone Institute of Virology and Immunology, University of California at San Francisco, California, United States of America
    PLoS ONE 2:e784. 2007

Scientific Experts

Detail Information

Publications156 found, 100 shown here

  1. ncbi Modulation of sirtuins: new targets for antiageing
    Merce Pallas
    Unitat de Farmacologia i Farmacognòsia i Institut de Biomedicina IBUB, Facultat de Farmacia, Universitat de Barcelona, Nucli Universitari de Pedralbes, E 08028 Barcelona, Spain
    Recent Pat CNS Drug Discov 3:61-9. 2008
    ..The protein implicated in this protective process is the silent information regulator 2 (SIR2, SIRT1 in mammals), an enzyme that belongs to a nicotinamide adenine dinucleotide (NAD)+-..
  2. ncbi The human Sir2 ortholog, SIRT2, is an NAD+-dependent tubulin deacetylase
    Brian J North
    Department of Physiology, University of California, San Francisco, 94141, San Francisco, CA, USA
    Mol Cell 11:437-44. 2003
    The silent information regulator 2 protein (Sir2p) of Saccharomyces cerevisiae is an NAD-dependent histone deacetylase that plays a critical role in transcriptional silencing...
  3. ncbi Proteomics-based identification of differentially expressed genes in human gliomas: down-regulation of SIRT2 gene
    Masaharu Hiratsuka
    Department of Molecular and Cell Genetics, Graduate School of Medical Science, Tottori University, Nishimachi 86, Yonago, Tottori 683 8503, Japan
    Biochem Biophys Res Commun 309:558-66. 2003
    ..We then focused on the cytoskeleton-related protein, SIRT2 (sirtuin homologue 2) tubulin deacetylase, which was down-regulated in gliomas. SIRT2 is located at 19q13...
  4. pmc SIRT2 maintains genome integrity and suppresses tumorigenesis through regulating APC/C activity
    Hyun Seok Kim
    Genetics of Development and Disease Branch, 10 9N105, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Cancer Cell 20:487-99. 2011
    ..To investigate the physiological functions of SIRT2 in development and tumorigenesis, we disrupted Sirt2 in mice...
  5. ncbi Human histone deacetylase SIRT2 interacts with the homeobox transcription factor HOXA10
    Nancy S Bae
    Laboratory of Molecular and Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    J Biochem 135:695-700. 2004
    ..Currently, there is no report on the interacting protein partner of a human Sir2 homolog, SIRT2. Here we show for the first time that SIRT2 interacts with the homeobox transcription factor, HOXA10, which was ..
  6. ncbi Characterization of five human cDNAs with homology to the yeast SIR2 gene: Sir2-like proteins (sirtuins) metabolize NAD and may have protein ADP-ribosyltransferase activity
    R A Frye
    Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, 15240, USA
    Biochem Biophys Res Commun 260:273-9. 1999
    ..Recombinant E. coli cobB and human SIRT2 sirtuin proteins were able to cause radioactivity to be transferred from [32P]NAD to bovine serum albumin (BSA)...
  7. ncbi Multiple histone deacetylases and the CREB-binding protein regulate pre-mRNA 3'-end processing
    Tadahiro Shimazu
    Chemical Genetics Laboratory, Discovery Research Institute, RIKEN, Wako, Saitama 351 0198, Japan
    J Biol Chem 282:4470-8. 2007
    ..Whereas CBP acetylated these proteins, HDAC1, HDAC3, HDAC10, SIRT1, and SIRT2 were involved in in vivo deacetylation...
  8. ncbi Characterization of a human gene with sequence homology to Saccharomyces cerevisiae SIR2
    G Afshar
    University of California, San Francisco, Radiation Oncology Research Laboratories, San Francisco, CA 94103, USA
    Gene 234:161-8. 1999
    ..In the present study, the complete sequence of a human gene, SIR2L, with homology to the yeast SIR2 gene is presented...
  9. doi Conserved metabolic regulatory functions of sirtuins
    Bjoern Schwer
    Gladstone Institute of Virology and Immunology, San Francisco, CA 94158, USA
    Cell Metab 7:104-12. 2008
    b>Silent information regulator 2 (Sir2) proteins, or sirtuins, are protein deacetylases/mono-ADP-ribosyltransferases found in organisms ranging from bacteria to humans...
  10. pmc Interphase nucleo-cytoplasmic shuttling and localization of SIRT2 during mitosis
    Brian J North
    Gladstone Institute of Virology and Immunology, University of California at San Francisco, California, United States of America
    PLoS ONE 2:e784. 2007
    The human NAD+-dependent protein deacetylase SIRT2 resides predominantly in the cytoplasm where it functions as a tubulin deacetylase...
  11. doi Sirt2 interacts with 14-3-3 beta/gamma and down-regulates the activity of p53
    Yun Hye Jin
    College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju, Republic of Korea
    Biochem Biophys Res Commun 368:690-5. 2008
    b>Sirt2 is a mammalian member of the Sirtuin family of NAD(+) (nicotinamide adenine dinucleotide)-dependent protein deacetylases. Although Sir-2...
  12. pmc Role for human SIRT2 NAD-dependent deacetylase activity in control of mitotic exit in the cell cycle
    Sylvia C Dryden
    Program in Molecular Biology and Genetics, Karmanos Cancer Institute and Wayne State University, Detroit, Michigan 48201, USA
    Mol Cell Biol 23:3173-85. 2003
    ..Our functional studies of human SIRT2, a homolog of the product of the yeast SIR2 gene, indicate that it plays a role in mitosis...
  13. ncbi FISH-mapping and genomic organization of the NAD-dependent histone deacetylase gene, Sirtuin 2 (Sirt2)
    Susanne Voelter-Mahlknecht
    Department of Hematology Oncology, University of Heidelberg Medical Center, D 69120 Heidelberg, Germany
    Int J Oncol 27:1187-96. 2005
    ..2 (SIRT2) is a nicotinamide adenine dinucleotide (NAD(+))-dependent deacetylase, which belongs to the Silent information regulator 2 (Sir2) family of sirtuin histone deacetylases (HDACs)...
  14. ncbi Conserved enzymatic production and biological effect of O-acetyl-ADP-ribose by silent information regulator 2-like NAD+-dependent deacetylases
    Margie T Borra
    Department of Biochemistry and Molecular Biology, Oregon Health and Sciences University, Portland, OR 97201 3098, USA
    J Biol Chem 277:12632-41. 2002
    b>Silent information regulator 2 (Sir2) family of enzymes has been implicated in many cellular processes that include histone deacetylation, gene silencing, chromosomal stability, and aging...
  15. ncbi SIRT2, a tubulin deacetylase, acts to block the entry to chromosome condensation in response to mitotic stress
    T Inoue
    Department of Human Genome Science, Graduate School of Medical Science, Tottori University, Yonago, Tottori, Japan
    Oncogene 26:945-57. 2007
    We previously identified SIRT2, an nicotinamide adenine dinucleotide (NAD)-dependent tubulin deacetylase, as a protein downregulated in gliomas and glioma cell lines, which are characterized by aneuploidy...
  16. pmc SirT2 is a histone deacetylase with preference for histone H4 Lys 16 during mitosis
    Alejandro Vaquero
    Howard Hughes Medical Institute, Piscataway, NJ 08854, USA
    Genes Dev 20:1256-61. 2006
    The mammalian cytoplasmic protein SirT2 is a member of the Sir2 family of NAD+-dependent protein deacetylases involved in caloric restriction-dependent life span extension...
  17. ncbi Substrate specificity and kinetic mechanism of the Sir2 family of NAD+-dependent histone/protein deacetylases
    Margie T Borra
    Department of Biomolecular Chemistry, University of Wisconsin, Madison, Wisconsin 53706 1532, USA
    Biochemistry 43:9877-87. 2004
    The Silent information regulator 2 (Sir2) family of enzymes consists of NAD(+)-dependent histone/protein deacetylases that tightly couple the hydrolysis of NAD(+) and the deacetylation of an acetylated substrate to form nicotinamide, the ..
  18. ncbi Enhancing cell longevity for cosmetic application: a complementary approach
    Marielle Moreau
    LVMH Recherche Parfums Christian Dior, St jean de braye, France
    J Drugs Dermatol 6:s14-9. 2007
    ..This study focuses on 1) yeast Kluyveromyces biopetides in stimulating the expression of sirtuin in human cutaneous cells and 2) the benefit for the skin of an active skin care product containing yeast Kluyveromyces biopetides...
  19. ncbi Mechanism-based inhibition of Sir2 deacetylases by thioacetyl-lysine peptide
    Brian C Smith
    Department of Chemistry, University of Wisconsin, Madison, Wisconsin 53706 1532, USA
    Biochemistry 46:14478-86. 2007
    ..deacetylation reaction, the thioacetyl-lysine peptide exhibited exceptionally potent inhibition of sirtuins Sirt1, Sirt2, Sirt3, and Hst2...
  20. ncbi MEC1-dependent redistribution of the Sir3 silencing protein from telomeres to DNA double-strand breaks
    K D Mills
    Massachusetts Institute of Technology, Department of Biology, Cambridge 02139, USA
    Cell 97:609-20. 1999
    The yeast Sir2/3/4p complex is found in abundance at telomeres, where it participates in the formation of silent heterochromatin and telomere maintenance...
  21. ncbi DNA damage triggers disruption of telomeric silencing and Mec1p-dependent relocation of Sir3p
    A D McAinsh
    Wellcome Trust Cancer Research Campaign Institute, Department of Zoology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QR, UK
    Curr Biol 9:963-6. 1999
    ..NHEJ also requires the SIR2, SIR3 and SIR4 gene products [4] [5], which are responsible for silencing at telomeres and the mating-type loci [6]...
  22. ncbi Acetyl-lysine analog peptides as mechanistic probes of protein deacetylases
    Brian C Smith
    Department of Chemistry, University of Wisconsin Madison, Madison, Wisconsin 53706 1532, USA
    J Biol Chem 282:37256-65. 2007
    ..tighter to Hst2 compared with acetyl-lysine peptide and showed measurable rates of catalysis with Hst2, Sirt1, Sirt2, and Sirt3, suggesting propionyl- and butyryl-lysine proteins may be sirtuin substrates in vivo...
  23. ncbi Sirtuins (histone deacetylases III) in the cellular response to DNA damage--facts and hypotheses
    Marcin Kruszewski
    Department of Radiobiology and Health Protection, Institute of Nuclear Chemistry and Technology, Dorodna 16, 03 195 Warszawa, Poland
    DNA Repair (Amst) 4:1306-13. 2005
    ..Homologues of the yeast gene SIR2 in mammalian cells code type III histone deacetylases (HDAC III, sirtuins), dependent on NAD(+) and inhibited by ..
  24. pmc Transition state of ADP-ribosylation of acetyllysine catalyzed by Archaeoglobus fulgidus Sir2 determined by kinetic isotope effects and computational approaches
    Yana Cen
    Department of Pharmacology, Weill Medical College of Cornell University, 1300 York Avenue, New York, New York 10065, USA
    J Am Chem Soc 132:12286-98. 2010
    ..A concerted yet highly asynchronous substitution mechanism forms the ADPR-peptidylimidate intermediate of the sirtuin deacetylation reaction...
  25. doi Sirtuins and their relevance to the kidney
    Chuan Ming Hao
    Division of Nephrology and Hypertension, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    J Am Soc Nephrol 21:1620-7. 2010
    Sirtuins (silent information regulator 2 [Sir2] proteins) belong to an ancient family of evolutionary conserved nicotinamide adenine dinucleotide (NAD)(+)-dependent enzymes with deacetylase and/or mono-ADP-ribosyltransferase activity...
  26. ncbi Crystal structure of a SIR2 homolog-NAD complex
    J Min
    W M Keck Structural Biology Laboratory, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA
    Cell 105:269-79. 2001
    The SIR2 protein family comprises a novel class of nicotinamide-adenine dinucleotide (NAD)-dependent protein deacetylases that function in transcriptional silencing, DNA repair, and life-span extension in Saccharomyces cerevisiae...
  27. pmc Conserved locus-specific silencing functions of Schizosaccharomyces pombe sir2+
    Lisa L Freeman-Cook
    Division of Biological Sciences, Section of Molecular Biology and UCSD Center for Cancer Research, University of California, San Diego, 92093 0347, USA
    Genetics 169:1243-60. 2005
    In Schizosaccharomyces pombe, three genes, sir2(+), hst2(+), and hst4(+), encode members of the Sir2 family of conserved NAD(+)-dependent protein deacetylases. The S...
  28. doi Linking sirtuins, IGF-I signaling, and starvation
    Valter D Longo
    Department of Biological Sciences, University of Southern California, 3715 McClintock Avenue, Los Angeles, CA 90089, USA
    Exp Gerontol 44:70-4. 2009
    ..Whereas other laboratories have proposed that sirtuins (Sir2 and its homologs), a family of conserved proteins which are NAD(+)-dependent histone deacetylases, can extend ..
  29. ncbi Mouse Sir2 homolog SIRT6 is a nuclear ADP-ribosyltransferase
    Gregory Liszt
    Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    J Biol Chem 280:21313-20. 2005
    Members of the Sir2 family of NAD-dependent protein deacetylases regulate diverse cellular processes including aging, gene silencing, and cellular differentiation...
  30. ncbi Mechanism of human SIRT1 activation by resveratrol
    Margie T Borra
    Department of Biomolecular Chemistry, University of Wisconsin Madison, Madison, Wisconsin 53706, USA
    J Biol Chem 280:17187-95. 2005
    ..Among the three enzymes tested (yeast Sir2, human SIRT1, and human SIRT2), only SIRT1 exhibited significant enzyme activation ( approximately 8-fold) using the commercially available ..
  31. ncbi Sir2 regulates histone H3 lysine 9 methylation and heterochromatin assembly in fission yeast
    Gurumurthy D Shankaranarayana
    Cold Spring Harbor Laboratory, P O Box 100, Cold Spring Harbor, NY 11724, USA
    Curr Biol 13:1240-6. 2003
    ..budding yeast Saccharomyces cerevisiae, deacetylation of histones in heterochromatic chromosomal domains requires Sir2, a phylogenetically conserved NAD(+)-dependent deacetylase...
  32. pmc Nicotinamide riboside and nicotinic acid riboside salvage in fungi and mammals. Quantitative basis for Urh1 and purine nucleoside phosphorylase function in NAD+ metabolism
    Peter Belenky
    Department of Genetics and Biochemistry, Dartmouth Medical School, Lebanon, New Hampshire 03756, USA
    J Biol Chem 284:158-64. 2009
    ..substrate of ADP-ribose transfer enzymes and sirtuins, the type III protein lysine deacetylases related to yeast Sir2. Supplementation of yeast cells with nicotinamide riboside extends replicative lifespan and increases Sir2-..
  33. doi Sirtuin mechanism and inhibition: explored with N(ε)-acetyl-lysine analogs
    Brett M Hirsch
    Department of Chemistry, University of Akron, 190 E Buchtel Commons, Akron, OH 44325, USA
    Mol Biosyst 7:16-28. 2011
    b>Silent information regulator 2 (Sir2) enzymes or sirtuins are a family of intracellular protein deacetylases that can catalyze the β-nicotinamide adenine dinucleotide (β-NAD(+))-dependent deacetylation of N(ε)-acetyl-lysine on protein ..
  34. ncbi Analysis of O-acetyl-ADP-ribose as a target for Nudix ADP-ribose hydrolases
    Louise A Rafty
    Oregon Health and Science University, Department of Biochemistry and Molecular Biology, Portland, Oregon 97201 3098, USA
    J Biol Chem 277:47114-22. 2002
    The Sir2 family of NAD(+)-dependent histone/protein deacetylases has been implicated in a wide range of biological activities, including gene silencing, life span extension, and chromosomal stability...
  35. doi Acetylation-dependent ADP-ribosylation by Trypanosoma brucei Sir2
    Terri M Kowieski
    Department of Biomolecular Chemistry, University of Wisconsin, School of Medicine and Public Health, Madison, Wisconsin 53706, USA
    J Biol Chem 283:5317-26. 2008
    ..Here we explored the mechanisms of ADP-ribosylation using the Trypanosoma brucei Sir2 homologue TbSIR2rp1 as a model for sirtuins that reportedly display both activities...
  36. ncbi SIR2: the biochemical mechanism of NAD(+)-dependent protein deacetylation and ADP-ribosyl enzyme intermediates
    Anthony A Sauve
    Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Ave F304, Bronx, NY 10461, USA
    Curr Med Chem 11:807-26. 2004
    The Sir2 family of enzymes is a recently described class of NAD(+)-dependent protein deacetylases that use NAD+ as a reactant to deacetylate acetyllysine residues of protein substrates to form the aminolysine sidechain and a novel product ..
  37. doi N(epsilon)-Modified lysine containing inhibitors for SIRT1 and SIRT2
    Tero Huhtiniemi
    School of Pharmacy, University of Eastern Finland, Kuopio Campus, PO Box 1627, 70211 Kuopio, Finland
    Bioorg Med Chem 18:5616-25. 2010
    ..been used as a probe for the screening of novel N(epsilon)-modified lysine containing inhibitors against SIRT1 and SIRT2. N(epsilon)-Selenoacetyl and N(epsilon)-isothiovaleryl were the most potent moieties found in this study, ..
  38. pmc Opposing effects of sirtuins on neuronal survival: SIRT1-mediated neuroprotection is independent of its deacetylase activity
    Jason A Pfister
    Department of Molecular and Cell Biology, University of Texas at Dallas, Richardson, TX, USA
    PLoS ONE 3:e4090. 2008
    ..Indeed, SIRT1 has been reported to protect against neuronal death, while SIRT2 promotes neurodegeneration...
  39. ncbi Chromosomal organization and fluorescence in situ hybridization of the human Sirtuin 6 gene
    Ulrich Mahlknecht
    Department of Hematology Oncology, University of Heidelberg Medical Center, D 69120 Heidelberg, Germany
    Int J Oncol 28:447-56. 2006
    ..Sirtuin 6 (SIRT6) is a member of the sirtuin deacetylases (sirtuins), which are derivatives of the yeast Silent information regulator 2 (Sir2) protein...
  40. ncbi 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
    Michael D Jackson
    Oregon Health and Science University, Department of Biochemistry and Molecular Biology, Portland, Oregopn 97201 3098, USA
    J Biol Chem 277:18535-44. 2002
    The Sir2 (silent information regulator 2) family of histone/protein deacetylases has been implicated in a wide range of biological activities, including gene silencing, life-span extension, and chromosomal stability...
  41. pmc "Clocks" in the NAD World: NAD as a metabolic oscillator for the regulation of metabolism and aging
    Shin Ichiro Imai
    Department of Developmental Biology, Washington University School of Medicine, St Louis, MO 63110, USA
    Biochim Biophys Acta 1804:1584-90. 2010
    SIR2 (silent information regulator 2) proteins, now called "sirtuins," are an evolutionarily conserved family of NAD-dependent protein deacetylases/ADP-ribosyltransferases...
  42. ncbi Fluorescence in situ hybridization and chromosomal organization of the human Sirtuin 7 gene
    Susanne Voelter-Mahlknecht
    Department of Hematology Oncology, University of Heidelberg Medical Center, D 69120 Heidelberg, Germany
    Int J Oncol 28:899-908. 2006
    ..is a member of the sirtuin family of protein deacetylases and is, therefore, a derivative of yeast Silent information regulator 2 (SIR2)...
  43. pmc The silencing protein SIR2 and its homologs are NAD-dependent protein deacetylases
    J Landry
    Department of Biochemistry and Cell Biology, State University of New York, Stony Brook, NY 11794 5215, USA
    Proc Natl Acad Sci U S A 97:5807-11. 2000
    Homologs of the chromatin-bound yeast silent information regulator 2 (SIR2) protein are found in organisms from all biological kingdoms...
  44. ncbi Sirtuin-targeting drugs: Mechanisms of action and potential therapeutic applications
    Ahmad Aljada
    Long Island University, Department of Biomedical Sciences, Brookville, NY 11548, USA
    Curr Opin Investig Drugs 11:1158-68. 2010
    ..sirtuins are NAD+-dependent histone/protein deacetylases that are similar to Saccharomyces cerevisiae silent information regulator 2 (Sir2)...
  45. ncbi Sirtuins: the 'magnificent seven', function, metabolism and longevity
    Nassim Dali-Youcef
    Institut de Génétique et de Biologie Moléculaire et Cellulaire de Strasbourg IGBMC, INSERM CNRS ULP, Illkirch, France
    Ann Med 39:335-45. 2007
    ..of histone deacetylases (HDACs) was named after their homology to the Saccharomyces cerevisiae gene silent information regulator 2 (Sir2)...
  46. pmc A buoyancy-based screen of Drosophila larvae for fat-storage mutants reveals a role for Sir2 in coupling fat storage to nutrient availability
    Tânia Reis
    Department of Molecular and Cell Biology, University of California, Berkeley, California, United States of America
    PLoS Genet 6:e1001206. 2010
    ..Among these was a sirtuin family member, Sir2. Sirtuins regulate the storage and metabolism of carbohydrates and lipids by deacetylating key regulatory proteins...
  47. pmc The 39-kDa poly(ADP-ribose) glycohydrolase ARH3 hydrolyzes O-acetyl-ADP-ribose, a product of the Sir2 family of acetyl-histone deacetylases
    Tohru Ono
    Pulmonary Critical Care Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892 1590, USA
    Proc Natl Acad Sci U S A 103:16687-91. 2006
    The silent information regulator 2 (Sir2) family of NAD-dependent N-acetyl-protein deacetylases participates in the regulation of gene silencing, chromatin structure, and longevity...
  48. ncbi Use of substrate analogs and mutagenesis to study substrate binding and catalysis in the Sir2 family of NAD-dependent protein deacetylases
    Ahlia N Khan
    Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada
    J Biol Chem 281:11702-11. 2006
    The Sir2 family of enzymes is highly conserved throughout evolution and functions in silencing, control of life span, apoptosis, and many other cellular processes...
  49. ncbi Sirtuin regulates cigarette smoke-induced proinflammatory mediator release via RelA/p65 NF-kappaB in macrophages in vitro and in rat lungs in vivo: implications for chronic inflammation and aging
    Se Ran Yang
    Department of Environmental Medicine, Division of Lung Biology and Disease, University of Rochester Medical Center, MRBX 3 11106, 601 Elmwood Ave, Box 850, Rochester, NY 14642, USA
    Am J Physiol Lung Cell Mol Physiol 292:L567-76. 2007
    The silent information regulator 2 (Sir2) family of proteins (sirtuins or SIRTs), which belong to class III histone/protein deacetylases, have been implicated in calorie restriction, aging, and inflammation...
  50. pmc The Drosophila melanogaster sir2+ gene is nonessential and has only minor effects on position-effect variegation
    Stefan U Aström
    Department of Developmental Biology, Wennergren Institute, Stockholm University, SE 106 91 Stockholm, Sweden
    Genetics 163:931-7. 2003
    Five Drosophila melanogaster genes belong to the highly conserved sir2 family, which encodes NAD(+)-dependent protein deacetylases...
  51. pmc Sirtuins in mammals: insights into their biological function
    Shaday Michan
    Department of Pathology, Paul F Glenn Laboratories for the Biological Mechanisms of Aging, Harvard Medical School, 77 Ave Louis Pasteur, Boston, MA, USA
    Biochem J 404:1-13. 2007
    ..Sirtuins are a conserved family of proteins found in all domains of life. The first known sirtuin, Sir2 (silent information regulator 2) of Saccharomyces cerevisiae, from which the family derives its name, regulates ribosomal DNA ..
  52. pmc SIRT2 suppresses adipocyte differentiation by deacetylating FOXO1 and enhancing FOXO1's repressive interaction with PPARgamma
    Fei Wang
    USDA ARS Children s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA
    Mol Biol Cell 20:801-8. 2009
    ..have previously reported that caloric restriction increases the expression of one of the seven mammalian sirtuins, SIRT2, in tissues such as white adipose tissue...
  53. pmc Mammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylation
    David B Lombard
    Howard Hughes Medical Institute, The Children s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Mol Cell Biol 27:8807-14. 2007
    Homologs of the Saccharomyces cerevisiae Sir2 protein, sirtuins, promote longevity in many organisms. Studies of the sirtuin SIRT3 have so far been limited to cell culture systems...
  54. doi SIRT2 regulates NF-κB dependent gene expression through deacetylation of p65 Lys310
    Karin M Rothgiesser
    Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Winterthurerstrase 190, 8057 Zurich, Switzerland
    J Cell Sci 123:4251-8. 2010
    ..In this study, we identified SIRT2 as a deacetylase of the transcription factor p65...
  55. pmc Nuclear export modulates the cytoplasmic Sir2 homologue Hst2
    Jeanne M Wilson
    Division of Biological Sciences, Section of Molecular Biology, University of California, San Diego, 9500 Gilman Drive, 0347, La Jolla, California 92093, USA
    EMBO Rep 7:1247-51. 2006
    Modulating transcription factors is crucial to executing sophisticated gene expression programs. The silent information regulator 2 (Sir2) family of NAD-dependent protein deacetylases influences transcription by targeting proteins such as ..
  56. pmc SirT1 inhibition reduces IGF-I/IRS-2/Ras/ERK1/2 signaling and protects neurons
    Ying Li
    Neuroscience Program, University of Southern California, Los Angeles, CA 90089 2520, USA
    Cell Metab 8:38-48. 2008
    Sirtuins are known to protect cells and extend life span, but our previous studies indicated that S. cerevisiae Sir2 can also increase stress sensitivity and limit life-span extension...
  57. ncbi Structural basis for the mechanism and regulation of Sir2 enzymes
    Jose L Avalos
    Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205 USA
    Mol Cell 13:639-48. 2004
    b>Sir2 proteins form a family of NAD(+)-dependent protein deacetylases required for diverse biological processes, including transcriptional silencing, suppression of rDNA recombination, control of p53 activity, regulation of acetyl-CoA ..
  58. pmc Genomewide screen for negative regulators of sirtuin activity in Saccharomyces cerevisiae reveals 40 loci and links to metabolism
    Ryan M Raisner
    Department of Biochemistry and Biophysics, University of California, San Francisco, California 94158 2200, USA
    Genetics 179:1933-44. 2008
    ..In Saccharomyces cerevisiae, the sirtuin Silent information regulator 2 (Sir2) promotes silent chromatin formation, suppresses recombination between repeats, and inhibits ..
  59. pmc The role of sirtuins in the control of metabolic homeostasis
    Jiujiu Yu
    Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS INSERM Université Louis Pasteur and Institut Clinique de la Souris, Illkirch, France
    Ann N Y Acad Sci 1173:E10-9. 2009
    ..the function of the sirtuin family, named after their homology to the Saccharomyces cerevisiae gene silent information regulator 2 (Sir2), has received a lot of attention, as their beneficial impact on longevity was linked to their ..
  60. pmc Where in the cell is SIRT3?--functional localization of an NAD+-dependent protein deacetylase
    William C Hallows
    Department of Biomolecular Chemistry, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53706, USA
    Biochem J 411:e11-3. 2008
    ..SIRT3 (sirtuin 3), a human homologue of Sir2 (silent information regulator 2), has been genetically linked to lifespan in the elderly...
  61. ncbi Structure of a Sir2 enzyme bound to an acetylated p53 peptide
    Jose L Avalos
    Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Mol Cell 10:523-35. 2002
    b>Sir2 proteins are NAD(+)-dependent protein deacetylases that play key roles in transcriptional regulation, DNA repair, and life span regulation...
  62. doi Development and characterization of lysine based tripeptide analogues as inhibitors of Sir2 activity
    Subhra Prakash Chakrabarty
    Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore 560064, India
    Bioorg Med Chem 17:8060-72. 2009
    ..protected lysine residues and their characterization as inhibitors of Plasmodiumfalciparum Sir2 activity...
  63. pmc Histone H4 lysine 16 acetylation regulates cellular lifespan
    Weiwei Dang
    Gene Expression and Regulation Program, The Wistar Institute Philadelphia, Pennsylvania 19104, USA
    Nature 459:802-7. 2009
    ..Yeast Sir2, the first member of the family to be found, establishes and maintains chromatin silencing by removing histone H4 ..
  64. ncbi Structure and substrate binding properties of cobB, a Sir2 homolog protein deacetylase from Escherichia coli
    Kehao Zhao
    The Wistar Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
    J Mol Biol 337:731-41. 2004
    ..Together, these studies suggest that substrate-specific binding by sirtuin proteins involves contributions from the zinc-binding domain of the enzyme and substrate regions distal to the acetyl-lysine-binding site...
  65. ncbi Silent information regulator 2alpha, a longevity factor and class III histone deacetylase, is an essential endogenous apoptosis inhibitor in cardiac myocytes
    Ralph R Alcendor
    Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark 07103, USA
    Circ Res 95:971-80. 2004
    Yeast silent information regulator 2 (Sir2), a nicotinamide adenine dinucleotide-dependent histone deacetylase (HDAC) and founding member of the HDAC class III family, functions in a wide array of cellular processes, including gene ..
  66. ncbi A novel chalcone polyphenol inhibits the deacetylase activity of SIRT1 and cell growth in HEK293T cells
    Tomoaki Kahyo
    Mitsubishi Kagaku Institute of Life Sciences MITILS, Machida, Tokyo, Japan
    J Pharmacol Sci 108:364-71. 2008
    SIRT1 is one of seven mammalian orthologs of yeast silent information regulator 2 (Sir2), and it functions as a nicotinamide adenine dinucleotide (NAD)-dependent deacetylase...
  67. pmc SIRT3, a human SIR2 homologue, is an NAD-dependent deacetylase localized to mitochondria
    Patrick Onyango
    Institute of Genetic Medicine, Department of Medicine, The Johns Hopkins University School of Medicine, 1064 Ross, 720 Rutland Avenue, Baltimore, MD 21205, USA
    Proc Natl Acad Sci U S A 99:13653-8. 2002
    The SIR2 (silent information regulator 2) gene family has diverse functions in yeast including gene silencing, DNA repair, cell-cycle progression, and chromosome fidelity in meiosis and aging...
  68. ncbi A sirtuin in the African trypanosome is involved in both DNA repair and telomeric gene silencing but is not required for antigenic variation
    Sam Alsford
    London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK
    Mol Microbiol 63:724-36. 2007
    b>Silent information regulator 2 (Sir2)-related proteins or sirtuins function as NAD(+)-dependent deacetylases or ADP ribosylases that target a range of substrates, thereby influencing chromatin structure and a diverse range of other ..
  69. ncbi Sirtuin 2 inhibitors rescue alpha-synuclein-mediated toxicity in models of Parkinson's disease
    Tiago Fleming Outeiro
    Alzheimer s Research Unit, MGH, Harvard Medical School, CNY 114, 16th Street, Charlestown, MA 02129, USA
    Science 317:516-9. 2007
    ..We identified a potent inhibitor of sirtuin 2 (SIRT2) and found that inhibition of SIRT2 rescued alpha-synuclein toxicity and modified inclusion morphology in a ..
  70. ncbi Sirtuin-independent effects of nicotinamide on lifespan extension from calorie restriction in yeast
    Mitsuhiro Tsuchiya
    Department of Biochemistry, University of Washington, Seattle, WA 98195, USA
    Aging Cell 5:505-14. 2006
    ..longevity in yeast: (i) suppression of rDNA recombination through activation of the sirtuin protein deacetylase Sir2 or (ii) decreased activity of the nutrient-responsive kinases Sch9 and TOR...
  71. ncbi Omega-3 fatty acids supplementation restores mechanisms that maintain brain homeostasis in traumatic brain injury
    Aiguo Wu
    Department of Physiological Science, University of California at Los Angeles UCLA, Los Angeles, California 90095, USA
    J Neurotrauma 24:1587-95. 2007
    ..The silent information regulator 2 (Sir2) has been implicated with maintaining genomic stability and cellular homeostasis under ..
  72. pmc Replication fork arrest and rDNA silencing are two independent and separable functions of the replication terminator protein Fob1 of Saccharomyces cerevisiae
    Narendra K Bairwa
    Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina 29425, USA
    J Biol Chem 285:12612-9. 2010
    ..Ter sites located in the intergenic spacer region of rDNA but also loads the NAD-dependent histone deacetylase Sir2 at Ter sites via a protein complex called RENT (regulator of nucleolar silencing and telophase exit)...
  73. ncbi HST1, a new member of the SIR2 family of genes
    M K Derbyshire
    Gene Regulation and Chromosome Biology Laboratory, NCI Frederick Cancer Research and Development Center, ABL Basic Research Program, Maryland 21702 1201, USA
    Yeast 12:631-40. 1996
    ..HST1 is very closely related to SIR2, showing 71% sequence identity over 84% of its length. Polymerase chain reaction with degenerate primers on S...
  74. pmc The deacetylase Sir2 from the yeast Clavispora lusitaniae lacks the evolutionarily conserved capacity to generate subtelomeric heterochromatin
    Cara A Froyd
    Biochemistry Department, Duke University, Durham, North Carolina, United States of America
    PLoS Genet 9:e1003935. 2013
    Deacetylases of the Sir2 or sirtuin family are thought to regulate life cycle progression and life span in response to nutrient availability...
  75. doi Sirt2 suppresses glioma cell growth through targeting NF-κB-miR-21 axis
    Ya Nan Li
    Department of Neurosurgery, Changhai Hospital, Second Military Medical University, Shanghai, China
    Biochem Biophys Res Commun 441:661-7. 2013
    ..Here we report that Sir2 was under expressed in human glioma tissues and cell lines. We found that Sirt2 overexpression decreased cell proliferation and colony formation capacity...
  76. pmc A unique class of conditional sir2 mutants displays distinct silencing defects in Saccharomyces cerevisiae
    Sandra N Garcia
    Division of Biology, UCSD Cancer Center and Center for Molecular Genetics, University of California, San Diego 92093 0347, USA
    Genetics 162:721-36. 2002
    ..The NAD(+)-dependent deacetylation of histones by the Sir2p family of proteins lends mechanistic insight into how SIR2 contributes to silencing...
  77. ncbi Variability of the SIRT3 gene, human silent information regulator Sir2 homologue, and survivorship in the elderly
    G Rose
    Department of Cell Biology, University of Calabria, Rende 87030, Italy
    Exp Gerontol 38:1065-70. 2003
    ..Studies in model organisms have demonstrated that SIR2 genes control lifespan, while no data are available regarding a possible role of SIRT3 in human longevity...
  78. ncbi Progressive loss of SIRT1 with cell cycle withdrawal
    Tsutomu Sasaki
    Department of Neuroscience, University of Virginia School of Medicine, Charlottesville, VA 22908, USA
    Aging Cell 5:413-22. 2006
    b>Sir2 is an NAD+-dependent deacetylase that regulates lifespan in yeast, worms and flies. The mammalian orthologs of Sir2 include SIRT1 in humans and mice...
  79. ncbi [Functional analysis of SIR2]
    Yoshiyuki Horio
    Department of Pharmacology, Sapporo Medical University, Sapporo 060 8556, Japan
    Nihon Yakurigaku Zasshi 122:30P-32P. 2003
    The yeast silent information regulator 2 (Sir2) is an NAD-dependent histone deacetylase and silences transcription at the mating type loci, telomeres and the ribosomal DNA. Over-expression of Sir2 extends the life span of yeast and C...
  80. pmc Structural basis for nicotinamide cleavage and ADP-ribose transfer by NAD(+)-dependent Sir2 histone/protein deacetylases
    Kehao Zhao
    The Wistar Institute, Department of Biochemistry and Biophysics, School of Medicine, and Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104
    Proc Natl Acad Sci U S A 101:8563-8. 2004
    b>Sir2 enzymes are broadly conserved from bacteria to humans and have been implicated to play roles in gene silencing, DNA repair, genome stability, longevity, metabolism, and cell physiology...
  81. doi Altered expression of SIRT gene family in head and neck squamous cell carcinoma
    Chi Chih Lai
    Division of Laryngology, Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123 Da Pi Rd, Niaosong District, 833 Kaohsiung City, Taiwan
    Tumour Biol 34:1847-54. 2013
    ..Our results demonstrated that the expression levels of SIRT1, SIRT2, SIRT3, SIRT5, SIRT6, and SIRT7 were significantly downregulated in cancerous tissues compared with noncancerous ..
  82. pmc Silent information regulator 2 potentiates Foxo1-mediated transcription through its deacetylase activity
    Hiroaki Daitoku
    Center for Tsukuba Advanced Research Alliance, University of Tsukuba, 1 1 1 Ten noudai, Tsukuba, Ibaraki 305 8577, Japan
    Proc Natl Acad Sci U S A 101:10042-7. 2004
    ..genes include the Forkhead transcription factor FOXO and the NAD-dependent histone deacetylase silent information regulator 2 (Sir2)...
  83. ncbi Small molecule regulation of Sir2 protein deacetylases
    Olivera Grubisha
    Department of Biomolecular Chemistry, University of Wisconsin, Madison, WI 53706 1532, USA
    FEBS J 272:4607-16. 2005
    The Sir2 family of histone/protein deacetylases (sirtuins) is comprised of homologues found across all kingdoms of life...
  84. pmc Phosphorylation regulates SIRT1 function
    Tsutomu Sasaki
    Neuroscience Graduate Program, University of Virginia, Charlottesville, Virginia, United States of America
    PLoS ONE 3:e4020. 2008
    b>SIR2 is an NAD(+)-dependent deacetylase [1]-[3] implicated in the regulation of lifespan in species as diverse as yeast [4], worms [5], and flies [6]...
  85. ncbi Drosophila Sir2 is required for heterochromatic silencing and by euchromatic Hairy/E(Spl) bHLH repressors in segmentation and sex determination
    Miriam I Rosenberg
    Division of Basic Sciences and Program in Developmental Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
    Cell 109:447-58. 2002
    Yeast SIR2 is a NAD+-dependent histone deacetylase required for heterochromatic silencing at telomeres, rDNA, and mating-type loci...
  86. ncbi Mechanism-based modulator discovery for sirtuin-catalyzed deacetylation reaction
    Weiping Zheng
    School of Pharmacy, Jiangsu University, Zhenjiang 212013, P R China
    Mini Rev Med Chem 13:132-54. 2013
    b>Silent information regulator 2 (Sir2) enzymes or sirtuins are a family of evolutionarily conserved intracellular protein deacetylases that can catalyze the acetyl group removal from the specific Nε-acetyl-lysine (AcK) side chains on a ..
  87. doi Tenovin-D3, a novel small-molecule inhibitor of sirtuin SirT2, increases p21 (CDKN1A) expression in a p53-independent manner
    Anna R McCarthy
    Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
    Mol Cancer Ther 12:352-60. 2013
    ..Recent studies show that tenovin-6, a small-molecule inhibitor of sirtuins SirT1 and SirT2, reduces tumor growth in vivo and eliminates leukemic stem cells in a murine model for chronic myelogenous ..
  88. doi Poly(ADP-ribose) polymerase mediates both cell death and ATP decreases in SIRT2 inhibitor AGK2-treated microglial BV2 cells
    Yexin Li
    School of Biomedical Engineering and Med X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, PR China
    Neurosci Lett 544:36-40. 2013
    Sirtuin 2 (SIRT2), a sirtuin family protein, is a tubulin deacetylase...
  89. doi Splitomicin inhibits fMLP-induced superoxide anion production in human neutrophils by activate cAMP/PKA signaling inhibition of ERK pathway
    Fu Chao Liu
    Department of Anesthesiology, Chang Gung Memorial Hospital, Linkou, Taiwan, ROC
    Eur J Pharmacol 688:68-75. 2012
    ..a cell-permeable lactone derived from naphthol and known to be a potent selective inhibitor of Sir2 (silent information regulator 2)...
  90. doi Design, synthesis, and biological activity of a novel series of human sirtuin-2-selective inhibitors
    Takayoshi Suzuki
    Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 13 Taishogun Nishitakatsukasa cho, Kita ku, Kyoto 603 8334, Japan
    J Med Chem 55:5760-73. 2012
    Selective inhibitors of human sirtuin 2 (SIRT2), a deacetylase, are candidate therapeutic agents for neurodegenerative diseases such as Parkinson's disease and Huntington's disease as well as potential tools for elucidating the ..
  91. doi Molecular modeling study for conformational changes of Sirtuin 2 due to substrate and inhibitor binding
    Sugunadevi Sakkiah
    Division of Applied Life Science BK21 program, Systems and Synthetic Agrobiotech Center SSAAC, Gyeongsang National University GNU, Gazha dong, Jinju, Republic of Korea
    J Biomol Struct Dyn 30:235-54. 2012
    Sirtuin is a member of NAD(+)-dependent deacetylase family. The structural details of Sirtuin 2 (SIRT2) complex will be very useful to discover the drug which might have beneficial effects on various diseases like cancer, diabetes, etc...
  92. doi Molecular docking and dynamics simulation, receptor-based hypothesis: application to identify novel sirtuin 2 inhibitors
    Sugunadevi Sakkiah
    Division of Applied Life Science BK21 program, Systems and Synthetic Agrobiotech Center SSAC, Plant Molecular Biology and Biotechnology Research Center PMBBRC, Research Institute of Natural Science RINS, Gyeongsang National University GNU, 501 Jinju daero, Gazha dong, Jinju 660 701, Korea
    Chem Biol Drug Des 80:315-27. 2012
    ..Owing to the absence of complex structure of sirtuin 2 (SIRT2), sirtinol was docked in the NAD(+) binding site and subjected to 5-nseconds molecular dynamics (MD) simulation...
  93. doi Nicotinamide inhibits growth of carcinogen induced mouse bladder tumor and human bladder tumor xenograft through up-regulation of RUNX3 and p300
    Wun Jae Kim
    Institute for Tumor Research and Department of Urology, College of Medicine, Cheongju, South Korea
    J Urol 185:2366-75. 2011
    ..We noted that the tumor suppressor RUNX3 is inactivated by promoter hypermethylation in human bladder cancer. We investigated whether reactivation of RUNX3 could suppress bladder cancer development in an animal model...
  94. ncbi Human Sir2-related protein SIRT1 associates with the bHLH repressors HES1 and HEY2 and is involved in HES1- and HEY2-mediated transcriptional repression
    Takehiko Takata
    Laboratory of Molecular and Cellular Assembly, Department of Biological Information, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 Nagatsuta, Midori ku, Yokohama 226 8501, Japan
    Biochem Biophys Res Commun 301:250-7. 2003
    ..bHLH repressor proteins, Hairy and Deadpan, bind to and function with the NAD(+)-dependent histone deacetylase, Sir2. Here we demonstrate that the human Sir2 homologue, SIRT1, also physically associates with the human bHLH repressor ..
  95. pmc Dietary obesity-associated Hif1α activation in adipocytes restricts fatty acid oxidation and energy expenditure via suppression of the Sirt2-NAD+ system
    Jaya Krishnan
    Institute of Cell Biology, ETH Zurich, Switzerland
    Genes Dev 26:259-70. 2012
    ..is linked to its capacity to suppress β-oxidation, in part, through transcriptional repression of sirtuin 2 (Sirt2) NAD(+)-dependent deacetylase...
  96. doi Deacetylation of FOXO3 by SIRT1 or SIRT2 leads to Skp2-mediated FOXO3 ubiquitination and degradation
    F Wang
    Children s Nutrition Research Center, Baylor College of Medicine, Houston, TX 77030, USA
    Oncogene 31:1546-57. 2012
    ..SIRT1 and SIRT2 deacetylate FOXO factors to regulate FOXO function...
  97. doi Sir2 is induced by oxidative stress in a yeast model of Huntington disease and its activation reduces protein aggregation
    M Alba Sorolla
    Departament de Ciencies Mediques Basiques, IRBLLEIDA, Universitat de Lleida, Facultat de Medicina, Spain
    Arch Biochem Biophys 510:27-34. 2011
    ..Oxidative stress, either endogenous as a result of mutant polyQ expression or exogenously generated, increases Sir2 levels...
  98. pmc Sir2 deletion prevents lifespan extension in 32 long-lived mutants
    Joe R Delaney
    Department of Pathology, University of Washington, Seattle, WA, USA
    Aging Cell 10:1089-91. 2011
    Activation of Sir2 orthologs is proposed to increase lifespan downstream of dietary restriction...
  99. pmc A possibility of nutriceuticals as an anti-aging intervention: activation of sirtuins by promoting mammalian NAD biosynthesis
    Shin Ichiro Imai
    Department of Developmental Biology, Washington University School of Medicine, Campus Box 8103, 660 South Euclid Avenue, St Louis, MO 63110, USA
    Pharmacol Res 62:42-7. 2010
    ..One potential target for the development of anti-aging drugs is the SIR2 (silent information regulator 2) family of NAD-dependent deacetylases/ADP-ribosyltransferases, called "sirtuins...
  100. pmc Structure-based development of novel sirtuin inhibitors
    Christine Schlicker
    Department of Biophysics, Ruhr University Bochum, Germany
    Aging (Albany NY) 3:852-72. 2011
    ..Virtual docking of a compound library into the peptide binding pockets of crystal structures of Sirt2, 3, 5 and 6 yielded compounds potentially discriminating between these isoforms...
  101. pmc The contribution of Toll-like receptor 2 to the innate recognition of a Leishmania infantum silent information regulator 2 protein
    Ricardo Silvestre
    Parasite Disease Group, Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal
    Immunology 128:484-99. 2009
    We have characterized a Leishmania protein belonging to the silent information regulator 2 (SIR2) family [SIR2 related protein 1 (SIR2RP1)] that might play an immunoregulatory role during infection through its capacity to trigger B-cell ..

Research Grants85

  1. The histone deacetylase SIRT6 functions as a co-repressor of Hif1 alpha in glucos
    Raul Mostoslavsky; Fiscal Year: 2010
    ..Little is known whether chromatin plays a role in carbohydrate flux. The yeast Sir2 protein is an NAD-dependent histone deacetylase that senses the metabolic status of the cell and functions as a ..
  2. ROLE OF SIRTUIN IN CIGARETTE SMOKE-INDUCED LUNG INFLAMMATION AND INJURY
    Irfan Rahman; Fiscal Year: 2010
    ..The founding member yeast Sir2 (ySir2, yeast silent information regulator 2) which is equivalent to human sirtuin1 (SIRT1) is essential for maintaining silent chromatin via the ..
  3. Protein Acetylation Signature of ES Cell Differentiation
    Alexey Terskikh; Fiscal Year: 2007
    ..In particular, we speculate that protein deacetylation mediated by the members of Sir2 family (mediated by the intracellular redox state) regulates the stem cell self-renewal vs...
  4. Mammalian SIRT6 Is A Master Regulator Of Glucose Homeostasis
    Raul Mostoslavsky; Fiscal Year: 2010
    ..Little is known whether chromatin plays a role in carbohydrate flux. The yeast Sir2 protein is an NAD-dependent histone deacetylase that senses the metabolic status of the cell and functions as a ..
  5. MECHANISM OF ACTION OF YEAST SILENCING COMPLEXES
    Danesh Moazed; Fiscal Year: 2007
    ..Information Regulator) complex, which mediates telomeric and mating-type silencing, the NAD-dependent deacetylase Sir2 associates with histone binding proteins Sir3 and Sir4, and all three proteins spread along the chromatin fiber in ..
  6. Role of Forkhead Proteins and Sirtuins in Metabolism
    ALEXANDER BANKS; Fiscal Year: 2007
    ..The silent information regulator 2 (Sir2 alpha) is a NAD+ dependent protein deacetylase that controls longevity in fruit flies and ..
  7. TRANSCRIPTIONAL SILENCING MECHANISMS
    JEF BOEKE; Fiscal Year: 2005
    ..The Sir2 protein is required for all forms of silencing, while Sir3 and Sir4 are required for telomeric and HM loci ..
  8. Reversible Protein Acetylation and Chromatin Function
    John M Denu; Fiscal Year: 2010
    The Sir2 (or sirtuin) protein family plays critical roles in aging, DMA repair, apoptosis, resistance to cell stress, and metabolism. However, the molecular basis for the varied phenotypes has remained elusive...
  9. Reversible Protein Acetylation and Chromatin Function
    John M Denu; Fiscal Year: 2010
    The Sir2 (or sirtuin) protein family plays critical roles in aging, DMA repair, apoptosis, resistance to cell stress, and metabolism. However, the molecular basis for the varied phenotypes has remained elusive...
  10. Regulation of mitochondrial metabolism by SIRT4
    Marcia Haigis; Fiscal Year: 2010
    ..The protein Sir2 (Silent Information Regulator) positively regulates aging in model organisms, and its NAD-dependent enzymatic ..
  11. Regulation of mitochondrial metabolism by SIRT4
    Marcia Haigis; Fiscal Year: 2009
    ..The protein Sir2 (Silent Information Regulator) positively regulates aging in model organisms, and its NAD-dependent enzymatic ..
  12. TWO NOVEL CPLA2 BINDING PROTEINS AND CELL DEATH
    Alice Sheridan; Fiscal Year: 2007
    ..phospholipase A2 interacts with 3 proteins, including Tip60, a Tip60 splice variant which we have called PLIP, and SIRT2. The goals of this grant have been to study the molecular basis for and roles of these proteins in mesangial cell ..
  13. TWO NOVEL CPLA2 BINDING PROTEINS AND CELL DEATH
    JOSEPH VINCENT BONVENTRE; Fiscal Year: 2010
    ..phospholipase A2 interacts with 3 proteins, including Tip60, a Tip60 splice variant which we have called PLIP, and SIRT2. The goals of this grant have been to study the molecular basis for and roles of these proteins in mesangial cell ..
  14. TWO NOVEL CPLA2 BINDING PROTEINS AND CELL DEATH
    Joseph Bonventre; Fiscal Year: 2009
    ..phospholipase A2 interacts with 3 proteins, including Tip60, a Tip60 splice variant which we have called PLIP, and SIRT2. The goals of this grant have been to study the molecular basis for and roles of these proteins in mesangial cell ..
  15. Sir2 regulation and chemical modulation
    Anthony Sauve; Fiscal Year: 2007
    ....
  16. Sir2 regulation and chemical modulation
    Anthony A Sauve; Fiscal Year: 2010
    ..abstract_text> ..
  17. Yeast Histone Acetylases and Sir2-like Deacetylases
    Rolf Sternglanz; Fiscal Year: 2004
    ..The specific aims for this period are: 1) to learn about the enzymatic mechanism of Sir2 and related proteins, recently demonstrated to be NAD-dependent protein deacetylases, 2) to determine if the role ..
  18. Molecular Study of sir-2 genes and Aging in C. elegans
    Leonard P Guarente; Fiscal Year: 2010
    ..The second is SIR2 and its related proteins (sirtuins), which have emerged in the past five years as important regulators of aging in ..
  19. Molecular Genetics of Caloric Restriction in Aging Flies
    Blanka Rogina; Fiscal Year: 2010
    ..In aim 1 of this proposal, we will determine if genetic manipulations of Indy, rpd3, and Sir2 genes, or CR, effect longevity by downregulation of the levels and activity of the OP I and III components in each ..
  20. KINETIC STUDIES OF ENZYME MECHANISMS
    WILLIAM WALLACE CLELAND; Fiscal Year: 2010
    ..NAD substrate, and at the carbonyl carbon and oxygen of the acetyl-peptide substrate in the reaction catalyzed by Sir2. Sir2 is a member of the silent regulator 2 family of protein deacetylases (sirtuins) which are involved in a host ..
  21. The Role of PARP-SIR2 Signaling in Heart Failure
    Mahesh Gupta; Fiscal Year: 2007
    ..As such, these studies are likely to provide new strategies for the management of heart failure. ..
  22. The Role of PARP-SIR2 Signaling in Heart Failure
    Mahesh P Gupta; Fiscal Year: 2010
    ..As such, these studies are likely to provide new strategies for the management of heart failure. ..
  23. The Role of PARP-SIR2 Signaling in Heart Failure
    Mahesh Gupta; Fiscal Year: 2009
    ..As such, these studies are likely to provide new strategies for the management of heart failure. ..
  24. Regulation WRN deacetylation by SIRT1 after DNA damage
    Jianyuan Luo; Fiscal Year: 2010
    ..b>Sir2, an NAD-dependent histone deacetylase has been proved to extend life span in yeast and C. elegans...
  25. Structure-Function of Protein Deacetylases
    Ronen Marmorstein; Fiscal Year: 2007
    ..The class III HDACs belong to the Sir2 protein family and show primary sequence and structural divergence with the class I/II HDACs...
  26. Integrated Microfluidics for Nerve Regeneration Studies using Laser Nano-Axotomy
    Adela Ben Yakar; Fiscal Year: 2007
    ..1) time-lapse in-vivo imaging of axon re-growth and degeneration of injured axons and (2) the role of the Sir2 family of genes and the drug resveratrol in regeneration of injured axons...
  27. Repressing HIF-1: targets and mechanisms
    Nianli Sang; Fiscal Year: 2010
    ..In addition, we have found that HDACIs stimulate the expression of HDAC3 and Sirt2, two potential repressors of HIF-1 activity...
  28. Repressing HIF-1: targets and mechanisms
    Nianli Sang; Fiscal Year: 2009
    ..In addition, we have found that HDACIs stimulate the expression of HDAC3 and Sirt2, two potential repressors of HIF-1 activity...
  29. Control of Sir2 by Nuclear NAD Salvage Pathways
    Jeffrey Smith; Fiscal Year: 2007
    ..For example, the Sir2 family of NAD-dependent protein deacetylases (the Sirtuins) couple the deacetylation of specific acetyl-lysine side ..
  30. Sir2 Regulates AMPK and Lipid Metabolism in Diabetes
    Mengwei Zang; Fiscal Year: 2009
    ..SIRT1, a mammalian ortholog of silent information regulator 2 (Sir2), is an NAD-dependent deacetylase mediates the effects of caloric restriction to expend lifespan...
  31. Sir2 Regulates AMPK and Lipid Metabolism in Diabetes
    Mengwei Zang; Fiscal Year: 2010
    ..SIRT1, a mammalian ortholog of silent information regulator 2 (Sir2), is an NAD-dependent deacetylase mediates the effects of caloric restriction to expend lifespan...
  32. Sir2 Regulates AMPK and Lipid Metabolism in Diabetes
    Mengwei Zang; Fiscal Year: 2010
    ..SIRT1, a mammalian ortholog of silent information regulator 2 (Sir2), is an NAD-dependent deacetylase mediates the effects of caloric restriction to expend lifespan...
  33. NAD Biosynthesis and the Regulation of Sirtuins
    JEFFREY SCOTT SMITH; Fiscal Year: 2010
    ..We have also recently identified thiamine biosynthesis as a metabolic pathway controlled by the Sir2 and Hst1 Sirtuins in response to changes in NAD and nicotinamide concentrations...
  34. The Sir2-p53-IGF link in mammalian life-span control
    Heidi Scrable; Fiscal Year: 2009
    ..This competitive revision application pertains to parent grant 1RO1 AG026094, The Sir2-p53-IGF link in mammalian life span control...
  35. NAD+ control of transcriptional silencing and longevity
    David Sinclair; Fiscal Year: 2007
    ..Yeast cells suppress this instability by forming "silent" heterochromatin at the rDNA locus. This process requires Sir2, an NAD+-dependent histone deacetylase...
  36. GENETIC ANALYSIS OF GENES CONTROLLING A POSITION EFFECT
    JASPER D RINE; Fiscal Year: 2010
    ..The NAD metabolite 2-0- Acetyl ADP Ribose, the product of the Sir2 histone deacetylase has gained much interest from in vitro suggestions for a role in silencing...
  37. Role of Chromatin in Genomic Maintenance
    David A Sinclair; Fiscal Year: 2010
    The SIR2/SIRT1 gene is an ancient gene that delays aging in diverse organisms, from yeast to flies, and potentially even mammals...
  38. Discovery of genes that extend yeast lifespan: Aging in immobilized cell reactors
    RAPHAEL ROSENZWEIG; Fiscal Year: 2007
    ..studies using yeast have led to the discovery of the role played by the silent information regulator protein Sir2 in modulating replicative lifespan, and the roles played by Ras2, Cyr1 and Sch9 in modulating chronological ..
  39. PATHOGENESIS OF CANDIDA GLABRATA IN THE URINARY TRACT
    Brendan Cormack; Fiscal Year: 2009
    ..part of this, we will determine if other NA-regulated genes (regulated by two NAD* dependent histone deacetylases Sir2 and Hst1) are in fact induced during UTI...
  40. PATHOGENESIS OF CANDIDA GLABRATA IN THE URINARY TRACT
    BRENDAN PATRICK CORMACK; Fiscal Year: 2010
    ..part of this, we will determine if other NA-regulated genes (regulated by two NAD* dependent histone deacetylases Sir2 and Hst1) are in fact induced during UTI...