SIRT2

Summary

Gene Symbol: SIRT2
Description: sirtuin 2
Alias: SIR2, SIR2L, SIR2L2, NAD-dependent protein deacetylase sirtuin-2, NAD-dependent 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. 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
  5. 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
  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 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
  8. ncbi Phylogenetic classification of prokaryotic and eukaryotic Sir2-like proteins
    R A Frye
    Pittsburgh V A Medical Center 132L, University, Pittsburgh, Pennsylvania 15240, USA
    Biochem Biophys Res Commun 273:793-8. 2000
  9. ncbi Structure of the histone deacetylase SIRT2
    M S Finnin
    Cellular Biochemistry and Biophysics Program, and Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Nat Struct Biol 8:621-5. 2001
  10. 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

Research Grants

  1. JEFFREY SCOTT SMITH; Fiscal Year: 2014
  2. Raul Mostoslavsky; Fiscal Year: 2014
  3. Weiwei Dang; Fiscal Year: 2015
  4. JEFFREY SCOTT SMITH; Fiscal Year: 2016
  5. Shin Ichiro Imai; Fiscal Year: 2016
  6. ROLE OF SIRTUIN IN CIGARETTE SMOKE-INDUCED LUNG INFLAMMATION AND INJURY
    Irfan Rahman; Fiscal Year: 2013
  7. Danesh Moazed; Fiscal Year: 2014
  8. Sir2 regulation and chemical modulation
    Anthony A Sauve; Fiscal Year: 2010
  9. Leonard P Guarente; Fiscal Year: 2016
  10. Marcia Haigis; Fiscal Year: 2014

Detail Information

Publications193 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. 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...
  5. 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...
  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 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...
  8. ncbi Phylogenetic classification of prokaryotic and eukaryotic Sir2-like proteins
    R A Frye
    Pittsburgh V A Medical Center 132L, University, Pittsburgh, Pennsylvania 15240, USA
    Biochem Biophys Res Commun 273:793-8. 2000
    ..The seven human sirtuin genes include all four classes: SIRT1, SIRT2, and SIRT3 are class I, SIRT4 is class II, SIRT5 is class III, and SIRT6 and SIRT7 are class IV.
  9. ncbi Structure of the histone deacetylase SIRT2
    M S Finnin
    Cellular Biochemistry and Biophysics Program, and Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Nat Struct Biol 8:621-5. 2001
    ..The 1.7 A crystal structure of the 323 amino acid catalytic core of human SIRT2, a homolog of yeast Sir2, reveals an NAD-binding domain, which is a variant of the Rossmann fold, and a smaller ..
  10. 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...
  11. 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...
  12. ncbi Sir2 regulates skeletal muscle differentiation as a potential sensor of the redox state
    Marcella Fulco
    Muscle Gene Expression Group, Laboratory of Muscle Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Mol Cell 12:51-62. 2003
    b>Sir2 is a NAD(+)-dependent histone deacetylase that controls gene silencing, cell cycle, DNA damage repair, and life span...
  13. 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 ..
  14. 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 ..
  15. 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)...
  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 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...
  18. ncbi Mitotic regulation of SIRT2 by cyclin-dependent kinase 1-dependent phosphorylation
    Brian J North
    Gladstone Institute of Virology and Immunology, University of California San Francisco, California 94158, USA
    J Biol Chem 282:19546-55. 2007
    ..Here, we demonstrate that SIRT2 is phosphorylated both in vitro and in vivo on serine 368 by the cell-cycle regulator, cyclin-dependent kinase 1, ..
  19. 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...
  20. 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...
  21. doi Cytosolic FoxO1 is essential for the induction of autophagy and tumour suppressor activity
    Ying Zhao
    Key Laboratory of Carcinogenesis and Translational Research Ministry of Education, Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing 100191, China
    Nat Cell Biol 12:665-75. 2010
    ..In response to stress, FoxO1 was acetylated by dissociation from sirtuin-2 (SIRT2), a NAD(+)-dependent histone deacetylase, and the acetylated FoxO1 bound to Atg7, an E1-like protein, to influence ..
  22. pmc Sir-two-homolog 2 (Sirt2) modulates peripheral myelination through polarity protein Par-3/atypical protein kinase C (aPKC) signaling
    Bogdan Beirowski
    Department of Genetics, Washington University School of Medicine, St Louis, MO 63110, USA
    Proc Natl Acad Sci U S A 108:E952-61. 2011
    ..to examine peripheral nerve myelination and identified the NAD(+)-dependent deacetylase Sir-two-homolog 2 (Sirt2) as a protein likely to be involved in myelination...
  23. 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...
  24. 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...
  25. pmc The histone deacetylase SIRT2 stabilizes Myc oncoproteins
    P Y Liu
    Children s Cancer Institute Australia for Medical Research, Randwick, Sydney, NSW 2031, Australia
    Cell Death Differ 20:503-14. 2013
    ..Here we demonstrated that the class III histone deacetylase SIRT2 was upregulated by N-Myc in neuroblastoma cells and by c-Myc in pancreatic cancer cells, and that SIRT2 enhanced N-..
  26. pmc The tumor suppressor SirT2 regulates cell cycle progression and genome stability by modulating the mitotic deposition of H4K20 methylation
    Lourdes Serrano
    Department of Genetics, The Human Genetics Institute of New Jersey, Rutgers University, Piscataway, New Jersey 08854, USA
    Genes Dev 27:639-53. 2013
    ..However, the mechanisms involved in the regulation of this event are not well understood. Here we show that SirT2 regulates H4K20me1 deposition through the deacetylation of H4K16Ac (acetylation of H4K16) and determines the ..
  27. pmc HDAC6 and SIRT2 regulate the acetylation state and oncogenic activity of mutant K-RAS
    Moon Hee Yang
    Molecular Pathology Unit, Center for Cancer Research, and Center for Systems Biology, Massachusetts General Hospital, 149 13 Street, Charlestown, MA 02129
    Mol Cancer Res 11:1072-7. 2013
    ..Here, the deacetylases HDAC6 and SIRT2 were shown to regulate the acetylation state of K-RAS in cancer cells...
  28. doi A role for SIRT2-dependent histone H3K18 deacetylation in bacterial infection
    Haig A Eskandarian
    Unité des Interactions Bactéries Cellules, Institut Pasteur, Paris, France
    Science 341:1238858. 2013
    ..We found that during infection with the bacterium Listeria monocytogenes, the host deacetylase sirtuin 2 (SIRT2) translocates to the nucleus, in a manner dependent on the bacterial factor InlB...
  29. pmc SIRT2 induces the checkpoint kinase BubR1 to increase lifespan
    Brian J North
    Department of Genetics, Paul F Glenn Laboratories for the Biological Mechanisms of Aging Harvard Medical School, Boston, MA, USA
    EMBO J 33:1438-53. 2014
    ..Here, we show that the loss of BubR1 levels with age is due to a decline in NAD(+) and the ability of SIRT2 to maintain lysine-668 of BubR1 in a deacetylated state, which is counteracted by the acetyltransferase CBP...
  30. 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...
  31. 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...
  32. 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...
  33. 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]...
  34. 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 ..
  35. 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...
  36. 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...
  37. pmc 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...
  38. 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...
  39. 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 ..
  40. 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...
  41. 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 ..
  42. 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...
  43. 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-..
  44. 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 ..
  45. 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...
  46. 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 ..
  47. 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...
  48. 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, ..
  49. 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...
  50. 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...
  51. 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...
  52. 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...
  53. 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...
  54. 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...
  55. 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...
  56. 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...
  57. 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 ..
  58. 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)...
  59. 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...
  60. 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)...
  61. 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...
  62. 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...
  63. 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...
  64. 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 ..
  65. 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 ..
  66. 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...
  67. 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...
  68. 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 ..
  69. 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 ..
  70. 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 ..
  71. 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...
  72. 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...
  73. 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...
  74. 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 ..
  75. 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 ..
  76. 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 ..
  77. 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...
  78. 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...
  79. 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 ..
  80. 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)...
  81. 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...
  82. ncbi Silencing factors participate in DNA repair and recombination in Saccharomyces cerevisiae
    Y Tsukamoto
    Department of Molecular Biology, Institute of Medical Science, University of Tokyo, Japan
    Nature 388:900-3. 1997
    ..b>Sir2 and Sir3, but not Sir1, were also found to participate in these processes...
  83. ncbi Histone deacetylases: unique players in shaping the epigenetic histone code
    Sam Thiagalingam
    Genetics and Molecular Medicine Programs and Pulmonary Center, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118, USA
    Ann N Y Acad Sci 983:84-100. 2003
    ..and class III HDACs form a structurally distinct class of NAD-dependent enzymes that are similar to the yeast SIR2 proteins...
  84. ncbi Differential regulation of the Sir2 histone deacetylase gene family by inhibitors of class I and II histone deacetylases
    S Kyrylenko
    Department of Neuroscience and Neurology, University of Kuopio, 70211 Kuopio, Finland
    Cell Mol Life Sci 60:1990-7. 2003
    ..b>SIRT2, SIRT4 and SIRT7 were upregulated, whereas SIRT1, SIRT5 and SIRT6 were downregulated by trichostatin A (TSA) and n-..
  85. ncbi Predominant expression of Sir2alpha, an NAD-dependent histone deacetylase, in the embryonic mouse heart and brain
    Jun Sakamoto
    Department of Pharmacology, Sapporo Medical University, School of Medicine, S1 W17, Chuo Ku, 060 8556, Sapporo, Japan
    FEBS Lett 556:281-6. 2004
    b>Sir2 is an NAD-dependent histone deacetylase that functions in longevity, gene silencing, heterochromatin formation, DNA repair, and suppression of DNA recombination in yeast...
  86. 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...
  87. ncbi Nutrient sensing and metabolic decisions
    Janet E Lindsley
    Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, Utah 84132 3201, USA
    Comp Biochem Physiol B Biochem Mol Biol 139:543-59. 2004
    ..In this review, we bring together information about five different nutrient-sensing pathways (AMP kinase, mTOR, PAS kinase, hexosamine biosynthesis and Sir2), highlighting their similarities, differences and roles in disease.
  88. ncbi Telomeric heterochromatin propagation and histone acetylation control mutually exclusive expression of antigenic variation genes in malaria parasites
    Lucio H Freitas-Junior
    Institut Pasteur, Biology of Host Parasite Interactions Unit CNRS URA2581, 25, rue du Dr Roux, 75724 Paris, France
    Cell 121:25-36. 2005
    ..One type of modification is mediated by a protein homologous to yeast Sir2 called PfSir2, which forms a chromosomal gradient of heterochromatin structure and histone hypoacetylation...
  89. 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...
  90. 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)...
  91. pmc Structure and function of the Saccharomyces cerevisiae Sir3 BAH domain
    Jessica J Connelly
    W M Keck Structural Biology Laboratory, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA
    Mol Cell Biol 26:3256-65. 2006
    ..Overexpression of this domain alone can lead to silencing as long as Sir1 is overexpressed and Sir2 and Sir4 are present...
  92. pmc Sirtuins deacetylate and activate mammalian acetyl-CoA synthetases
    William C Hallows
    Department of Biomolecular Chemistry, University of Wisconsin Medical School, 1300 University Avenue, Madison, WI 53706, USA
    Proc Natl Acad Sci U S A 103:10230-5. 2006
    b>Silent Information Regulator 2 (Sir2) enzymes (or sirtuins) are NAD(+)-dependent deacetylases that modulate gene silencing, aging and energy metabolism. Previous work has implicated several transcription factors as sirtuin targets...
  93. pmc Individual subunits of the Ssn6-Tup11/12 corepressor are selectively required for repression of different target genes
    Fredrik Fagerström-Billai
    School of Life Sciences, Södertörns högskola, SE 141 89 Huddinge, Sweden
    Mol Cell Biol 27:1069-82. 2007
    ..Interestingly, a subset of corepressor target genes, including direct target genes affected by Ssn6 overexpression, is associated with the function of class II (Clr3) and III (Hst4 and Sir2) HDACs.
  94. ncbi Sirtuin 2, a mammalian homolog of yeast silent information regulator-2 longevity regulator, is an oligodendroglial protein that decelerates cell differentiation through deacetylating alpha-tubulin
    Wenbo Li
    Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597
    J Neurosci 27:2606-16. 2007
    ..Here, we show that sirtuin 2 (SIRT2), a mammalian SIR2 homolog, is an oligodendroglial cytoplasmic protein and localized to the outer and juxtanodal ..
  95. ncbi Nicotinamide riboside promotes Sir2 silencing and extends lifespan via Nrk and Urh1/Pnp1/Meu1 pathways to NAD+
    Peter Belenky
    Departments of Genetics and Biochemistry and the Norris Cotton Cancer Center, Dartmouth Medical School, Rubin 733 HB7937, Lebanon, NH 03756, USA
    Cell 129:473-84. 2007
    Although NAD(+) biosynthesis is required for Sir2 functions and replicative lifespan in yeast, alterations in NAD(+) precursors have been reported to accelerate aging but not to extend lifespan...
  96. 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...
  97. ncbi Is Sirt1 a miracle bullet for longevity?
    Shin Ichiro Imai
    Department of Molecular Biology and Pharmacology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA
    Aging Cell 6:735-7. 2007
    The Sir2 (silent information regulator 2) family of nicotinamide adenine dinucleotide-dependent deacetylases has been implicated in the regulation of aging and longevity across a wide variety of organisms...
  98. pmc Structural and synthetic investigations of tanikolide dimer, a SIRT2 selective inhibitor, and tanikolide seco-acid from the Madagascar marine cyanobacterium Lyngbya majuscula
    Marcelino Gutierrez
    Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography and the Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, La Jolla, California 92037, USA
    J Org Chem 74:5267-75. 2009
    Tanikolide seco-acid 2 and tanikolide dimer 3, the latter a novel and selective SIRT2 inhibitor, were isolated from the Madagascar marine cyanobacterium Lyngbya majuscula...
  99. pmc Resveratrol attenuates mitochondrial oxidative stress in coronary arterial endothelial cells
    Zoltan Ungvari
    Department of Physiology, New York Medical College, Valhalla, New York, USA
    Am J Physiol Heart Circ Physiol 297:H1876-81. 2009
    ..mtROS production in CAECs, an effect that was prevented by the knockdown of the protein deacetylase silent information regulator 2/sirtuin 1 (SIRT1), an intracellular target of resveratrol...
  100. doi Sirtuin regulation in calorie restriction
    Xiaolei Qiu
    Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA 94720, USA
    Biochim Biophys Acta 1804:1576-83. 2010
    ..studies in model organisms began to uncover the molecular regulation of calorie restriction response, with the gene SIR2 playing an essential role...
  101. pmc The Sir2-Sum1 complex represses transcription using both promoter-specific and long-range mechanisms to regulate cell identity and sexual cycle in the yeast Kluyveromyces lactis
    Meleah A Hickman
    Institute for Genome Sciences and Policy, Duke University, Durham, North Carolina, United States of America
    PLoS Genet 5:e1000710. 2009
    Deacetylases of the Sir2 family regulate lifespan and response to stress...

Research Grants64

  1. JEFFREY SCOTT SMITH; Fiscal Year: 2014
    ..b>Sir2 from the budding yeast, Saccharomyces cerevisiae, is the founding family member and has been extensively studied ..
  2. Raul Mostoslavsky; Fiscal Year: 2014
    ..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 ..
  3. Weiwei Dang; Fiscal Year: 2015
    ..However, it has become exceedingly difficult to explorer more pro-lifespan regulators, like Sir2, because disruption of many genes that impair critical pathways naturally result in shorter lifespan and they may ..
  4. JEFFREY SCOTT SMITH; Fiscal Year: 2016
    ..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...
  5. Shin Ichiro Imai; Fiscal Year: 2016
    ..We have been interested in the evolutionarily conserved SIR2 (silent information regulator 2) family of NAD-dependent deacetylases/ADP-ribosyltransferases, also called "sirtuins," as a critical ..
  6. ROLE OF SIRTUIN IN CIGARETTE SMOKE-INDUCED LUNG INFLAMMATION AND INJURY
    Irfan Rahman; Fiscal Year: 2013
    ..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 ..
  7. Danesh Moazed; Fiscal Year: 2014
    ..The SIR complex is composed of the NAD-dependent deacetylase Sir2, the histone binding protein Sir3, and an adaptor protein Sir4...
  8. Sir2 regulation and chemical modulation
    Anthony A Sauve; Fiscal Year: 2010
    ..abstract_text> ..
  9. Leonard P Guarente; Fiscal Year: 2016
    ..Three (SIRT1, 6, and 7) are primarily nuclear, three (SIRT3-5) are mitochondrial and SIRT2 is cytoplasmic...
  10. Marcia Haigis; Fiscal Year: 2014
    ..The protein Sir2 (Silent Information Regulator) positively regulates aging in model organisms, and its NAD-dependent enzymatic ..
  11. Transcriptional Regulation by a Deacetylase, CobB, in a Periodontopathogen
    DAVID J KOLODRUBETZ; Fiscal Year: 2013
    ..Members of the sirtuin (Sir2-like) family of proteins are found in all three domains of life...
  12. DAVID SUNG WEN YU; Fiscal Year: 2016
    ..Preliminary data identify SIRT2, a sirtuin family deacetylase, as a novel regulator of the RSR...
  13. Chemical Tools to Visualize Sirtuin Activity in Cells
    Anthony A Sauve; Fiscal Year: 2013
    ..b>SIRT2 is cytosolic...
  14. Albert R La Spada; Fiscal Year: 2016
    ..We demonstrated a genetic and functional interaction between Sgf73 and Sir2, the original member of a family of proteins known as the "sirtuins", and noted a physical interaction between ..
  15. Molecular Genetics of Caloric Restriction in Aging Flies
    Blanka Rogina; Fiscal Year: 2013
    ..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 ..
  16. 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 ..
  17. 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...
  18. Mechanism of Sir2 Family of NAD+-dependent Deacetylases
    Margie Borra; Fiscal Year: 2005
    The silent information regulator 2 (Sir2) family of enzymes is conserved in organisms ranging from some bacteria to human...
  19. Discovery of genes that extend yeast lifespan: Aging in immobilized cell reactors
    RAPHAEL ROSENZWEIG; Fiscal Year: 2009
    ..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 ..
  20. Regulation WRN deacetylation by SIRT1 after DNA damage
    JIANYUAN JACK LUO; Fiscal Year: 2012
    ..b>Sir2, an NAD-dependent histone deacetylase has been proved to extend life span in yeast and C. elegans...
  21. The Effects of Ethanol on Microtubules during Mouse Pre-implantation Development
    Yixian Zheng; Fiscal Year: 2012
    ..The NAD-dependent sirtuin SIRT2 and the histone deacetylase HDAC6 are responsible for regulating this acetylation...
  22. Stephen L Helfand; Fiscal Year: 2016
    ..life span extending effect of CR/DR is mediated by alterations in the activity of the histone deacetylases Rpd3 and Sir2, and the transcription factor p53...
  23. Raul Mostoslavsky; Fiscal Year: 2014
    ..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 ..
  24. Mammalian Sir2 Function in Pancreatic Beta Cells
    Shin Ichiro Imai; Fiscal Year: 2012
    ....
  25. Brain epigenetic mechanisms in alcohol dependence
    SUBHASH PANDEY; Fiscal Year: 2009
    ..and trichostatin A (ISA) is a potent inhibitor of class I and II HDACs, but not the class III HDACs [silent information regulator 2(Sir2) protein family] which requires a cofactor, nicotinamide-adenine dinucleotide (NAD), for ..
  26. The Regulation of Mitochondrial Function by SIRT3
    Qiang Tong; Fiscal Year: 2010
    ..b>Sir2, which possesses the NAD- dependent deacetylase and ADP-ribosyltransferase activities, mediates the effect of ..
  27. Sir2 Regulates AMPK and Lipid Metabolism in Diabetes
    Mengwei Zang; Fiscal Year: 2012
    ..SIRT1, a mammalian ortholog of silent information regulator 2 (Sir2), is an NAD-dependent deacetylase mediates the effects of caloric restriction to expend lifespan...
  28. Does SIRT1 regulate mammalian health and longevity?
    Joseph A Baur; Fiscal Year: 2011
    ..It has been proposed that the Sir2/SIRT1 deacetylase is a critical mediator of CR's effects and indeed, Sir2 is necessary for lifespan extension ..
  29. Nihal Ahmad; Fiscal Year: 2016
    ..Over the past decade, SIRT1, a member of SIR2 family of sirtuin class III histone deacetylases, has garnered tremendous attention in neoplastic transformation ..
  30. Repressing HIF-1: targets and mechanisms
    Nianli Sang; Fiscal Year: 2012
    ..In addition, we have found that HDACIs stimulate the expression of HDAC3 and Sirt2, two potential repressors of HIF-1 activity...
  31. Role of Chromatin in Genomic Maintenance
    David A Sinclair; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): The SIR2/SIRT1 gene is an ancient gene that delays aging in diverse organisms, from yeast to flies, and potentially even mammals...
  32. Metabolic Cellular Stress and its Regulatory Mechanism in Diabetic Embryopathy
    Peixin Yang; Fiscal Year: 2012
    ..NTDs);3) PKCa gene deletion, a p70S6K1 inhibitor, an ER chaperone (4-PBA) and overexpression of sirtuin 2 (SIRT2) histone deacetylase in the neural tube, all reduce hyperglycemia- induced NTDs;4) both p70S6K1 inhibitor and SIR2 ..
  33. A Chemical Biology Approach for Discovery of HDAC Inhibitors
    Taro Amagata; Fiscal Year: 2012
    ..SIRT1 regulates several tumor suppressor genes such as p53 and forkhead box (FOXO) whereas SIRT2 regulates a G2/M mitotic checkpoint and 1-tubulin stability...
  34. Mitochondrial Genetics of Aging in Drosophila
    David M Rand; Fiscal Year: 2013
    ..We will exploit these mtDNA replacement strains to test this hypothesis using epistasis experiments with the Rpd3 - Sir2 and TOR pathways that play important roles in nutrient-based changes in longevity...
  35. Functions and Interactions dFOXO in Drosopila Aging
    Marc Tatar; Fiscal Year: 2010
    ..through genetic analysis how longevity is affected by the interaction of dFOXO with the histone deactylase SIR2, with the translation factor binding protein 4e-BP, and with the insulin receptor substrate homolog chico and (4) ..
  36. Vera Gorbunova; Fiscal Year: 2015
    ..Furthermore, we found that SIRT6, a mammalian homolog of yeast longevity gene Sir2, promotes DSB repair under oxidative stress and is able to complement senescence-related decline in repair...
  37. Development of cambinol analogues as antilymphoma agents
    Antonio Bedalov; Fiscal Year: 2012
    ..and evaluate analogues of cambinol, a small molecule inhibitor of human NAD-dependent deacetylases SIRT1 and SIRT2, and to validate SIRT1 and/or SIRT2 as therapeutic targets in germinal center lymphomas...
  38. Genome-wide Analysis of Aging in Yeast
    Brian K Kennedy; Fiscal Year: 2010
    ..multiple deletions, has led to the conclusion that caloric restriction can extend yeast replicative life span by a SIR2-independent, ERC-independent mechanism...
  39. Marc R Gartenberg; Fiscal Year: 2015
    ..The laboratory recently discovered that Sir2, the evolutionarily conserved protein deacetylase responsible for yeast heterochromatin assembly, retains cohesin ..
  40. Cell polarity and aging
    JOSE RICARDO MCFALINE FIGUEROA; Fiscal Year: 2012
    ..Finally, other studies support a role for SIR2, a conserved lifespan regulator and the actin cytoskeleton in the localization of oxidatively-damaged proteins, and ..
  41. Regulation of SirT1 by Deleted in Breast Cancer 1 (DBC1)
    Zhenkun Lou; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): SirT1, the mammalian ortholog of yeast Sir2, regulates a variety of cellular processes in mammalian cells, such as cellular stress response and energy metabolism, contributing to possible anti-aging ..
  42. Biochemical and genomic studies of histone deacetylases
    BRADLEY BERNSTEIN; Fiscal Year: 2006
    ..The yeast HDACs RPD3 and SIR2 have previously been shown to have opposite effects on silencing and aging...
  43. Molecular Mechanisms of Mammalian SIRT6 Function
    Katrin F Chua; Fiscal Year: 2010
    b>Sir2 (Silent Information Regulator-2) proteins function in aging and lifespan regulation in multiple model organisms...
  44. Eduardo N Chini; Fiscal Year: 2016
    ..In the second cycle of funding for our grant entitled, [unreadable]The Sir2[unreadable]p53[unreadable]IGF link in mammalian life span control,[unreadable] we will pursue studies to delineate ..
  45. KINETIC STUDIES OF ENZYME MECHANISMS
    Ivan Rayment; Fiscal Year: 2013
    ..1. Sir2 is an important enzyme in cell signaling that transfers acetyl groups from acetylated lysine in proteins to the ..
  46. Cross regulation between JNK and Insulin Signaling
    Dirk Bohmann; Fiscal Year: 2010
    ..To test the hypothesis that the life span regulator Sir2 cooperates with JNK in the activation of Foxo and the mediation of its biological effects.
  47. Peptidomimetic Human SIRT1 Enzyme Inhibitors
    Weiping Zheng; Fiscal Year: 2010
    ..Protein deacetylation can be catalyzed by a class of evolutionarily conserved intracellular Sir2 family enzymes. In humans, seven Sir2 orthologues, i.e. SIRT1-7, have been identified...
  48. Epigenetics of Dietary and Body Fat in Drosophila
    Douglas Ruden; Fiscal Year: 2006
    ..The Aims are: 1) To identify genes with altered chromatin states (altered Rpd3 or Sir2 binding sites) in a multi-generational study in which high or low body fat isogenic strains of Drosophila are fed a ..
  49. MICHAEL JAMES VAN METER; Fiscal Year: 2015
    ..SIRT6 is one of seven mammalian homologues of the yeast gene, SIR2, which was identified for its ability to regulate lifespan and promote genomic stability...
  50. The Role of Sirt1 in Neonatal Hypoxic Ischemic Brain Injury
    ALLYSON EVANS VAUGHN; Fiscal Year: 2010
    ..Sirti, the mammalian orthologue of the yeast NAD+depenedent protein deacetylase, Sir2, has proven to regulate resistance to a variety of cellular stresses, in part by inhibiting apoptosis...
  51. 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 ..
  52. JOSEPH VINCENT BONVENTRE; Fiscal Year: 2016
    ..In the second Specific Aim we will define the role of sirtuin T2 (SIRT2) in the response to injury and to relate SIRT2 expression and activity to G2/M transition control and the ..
  53. Chromatin Regulation by Deacetylation and SUMO-Targeted Ubiquitin Ligation
    Lorraine Pillus; Fiscal Year: 2012
    ..The proposed research builds on the lab's recent discovery that the Sir2 deacetylase is physically and functionally linked to a STUbL activity catalyzed by the Slx5-Slx8 complex...
  54. Bioengineering challenges for platelet production from hematopoietic stem cells
    William M Miller; Fiscal Year: 2010
    ..the hypothesis, based on our preliminary results, that NIC increases Mk ploidy via inhibition of the SIRT1 and SIRT2 Class III histone/protein deacetylases...
  55. JASPER D RINE; Fiscal Year: 2016
    ..of metabolic intermediates as mediators of epigenetics and cancer, the PI will resolve the paradoxical role of Sir2, the founding member of the sirtuin family of deacetylases, with respect to the potential role of 2-O-acetyl-ADP-..
  56. RAGHAVAN PILLAI RAJU; Fiscal Year: 2016
    ..genomics in the rat resulted in the identification of a novel pathway involving Sirt1 (mammalian homolog of sir2-silent mating type information regulation 2) in hemorrhagic injury...
  57. Robert S Weiss; Fiscal Year: 2015
    ..to be regulated by the mitochondrial protein Sirt5, a member of the Sir2 family of proteins (for Silent information regulator 2)...
  58. The Role of Drosophila SIR2 in gene silencing, DNA meta*
    PETER HARTE; Fiscal Year: 2005
    The long term goal of the proposed research is to understand the role of the Drosophila SIR2 protein in gene silencing and investigate its possible role in lifespan-extension by caloric restriction (CR) in higher eukaryotes...
  59. STRUCTURAL STUDIES OF DNA REPAIR PROTEINS
    TOM E ELLENBERGER; Fiscal Year: 2011
    ..order to explore other diverse functions of the repair endonuclease ERCC1-XPF, and 3) the enzymatic regulation of Sir2, a protein deacetylase with diverse activities, including DNA repair functions...
  60. 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...
  61. TWO NOVEL CPLA2 BINDING PROTEINS AND CELL DEATH
    Alice Sheridan; Fiscal Year: 2005
    cPLA2 interacts with three proteins, including TipGO, a TipGO splice variant which we have called PLIP, and SIRT2. The goals of this application have been to study the molecular basis for and roles of these proteins in mesangial cell ..
  62. The Foxo3/Sirt1 complex in oxidative stress-induced neuronal death
    DANIEL R CALNAN; Fiscal Year: 2010
    ..In response to oxidative stress stimuli, FoxoS interacts with Sirtl, a member of the Sir2 family of deacetylases that extend longevity in invertebrates...