SIRT5

Summary

Gene Symbol: SIRT5
Description: sirtuin 5
Alias: SIR2L5, NAD-dependent deacetylase sirtuin-5, NAD-dependent lysine demalonylase and desuccinylase sirtuin-5, mitochondrial, NAD-dependent protein deacylase sirtuin-5, mitochondrial, SIR2-like protein 5, regulatory protein SIR2 homolog 5, silent mating type information regulation 2, S.cerevisiae, homolog 5, sir2-like 5, sirtuin type 5
Species: human

Top Publications

  1. ncbi Assignment of the NAD-dependent deacetylase sirtuin 5 gene (SIRT5) to human chromosome band 6p23 by in situ hybridization
    U Mahlknecht
    Department of Hematology Oncology, University of Heidelberg Medical Center, Heidelberg, Germany
    Cytogenet Genome Res 112:208-12. 2006
  2. doi Substrates and regulation mechanisms for the human mitochondrial sirtuins Sirt3 and Sirt5
    Christine Schlicker
    Laboratory of Biochemistry, Department of Physiological Chemistry, Ruhr University Bochum, Universitaetsstrasse 150, 44801 Bochum, Germany
    J Mol Biol 382:790-801. 2008
  3. doi Structural insights of SIR2rp3 proteins as promising biotargets to fight against Chagas disease and leishmaniasis
    Lionel Sacconnay
    Pharmacochemistry and Phytochemistry and Bioactive Natural Products, School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest Ansermet 30, CH 1211 Geneva 4, Switzerland
    Mol Biosyst 9:2223-30. 2013
  4. doi An acetylome peptide microarray reveals specificities and deacetylation substrates for all human sirtuin isoforms
    David Rauh
    Department of Enzymology, Institute for Biochemistry and Biotechnology, Martin Luther University, Kurt Mothes Staße 3, 06120 Halle Saale, Germany
    Nat Commun 4:2327. 2013
  5. doi SIRT5 Regulates the Mitochondrial Lysine Succinylome and Metabolic Networks
    Matthew J Rardin
    Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USA
    Cell Metab 18:920-33. 2013
  6. pmc Widespread and enzyme-independent Nε-acetylation and Nε-succinylation of proteins in the chemical conditions of the mitochondrial matrix
    Gregory R Wagner
    From the Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana 46202 and
    J Biol Chem 288:29036-45. 2013
  7. pmc Oxygen flux analysis to understand the biological function of sirtuins
    Dongning Wang
    Sarah W Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, NC, USA
    Methods Mol Biol 1077:241-58. 2013
  8. pmc Ethanol metabolism modifies hepatic protein acylation in mice
    Kristofer S Fritz
    Department of Pharmaceutical Sciences, University of Colorado Denver Anschutz Medical Campus, Aurora, Colorado, United States of America
    PLoS ONE 8:e75868. 2013
  9. pmc Metabolic characterization of a Sirt5 deficient mouse model
    Jiujiu Yu
    Laboratory of Integrative and Systems Physiology LISP NCEM, School of Life Sciences, Ecole Polytechnique Federale de Lausanne EPFL, 1015 Lausanne, Switzerland
    Sci Rep 3:2806. 2013
  10. doi Effect of breed on the expression of Sirtuins (Sirt1-7) and antioxidant capacity in porcine brain
    Y Ren
    1 Key laboratory of Animal Nutrition and Feed Science of Ministry of Agriculture, Key Laboratory of Feed and Animal Nutrition of Zhejiang Province, Institute of Feed Science, Zhejiang University, No 866 Yuhangtang Road, Hangzhou 310058, People s Republic of China
    Animal 7:1994-8. 2013

Scientific Experts

  • R A Frye
  • Susanne Voelter-Mahlknecht
  • Ondrej Slaby
  • Susan Costantini
  • Bruce G Szczepankiewicz
  • Matthew D Hirschey
  • Xiaoling Li
  • L Tomanek
  • U Mahlknecht
  • ERIC M VERDIN
  • C S Lieber
  • Hening Lin
  • Melanie Gertz
  • Christin Glorioso
  • Clemens Steegborn
  • Frank Fischer
  • Bin He
  • Christin A Glorioso
  • Yasuhiko Nakamura
  • David B Lombard
  • Benjamin Suenkel
  • Wenjuan He
  • John C Newman
  • Jintang Du
  • Johan Auwerx
  • Masahito Ogura
  • Takashi Nakagawa
  • Yi Zhang
  • Chao Peng
  • Yeyun Zhou
  • Linh Ho
  • Nobuya Inagaki
  • Leonard Guarente
  • Daisuke Tanaka
  • Christine Schlicker
  • Eriko Michishita
  • Matthew J Rardin
  • Kristofer S Fritz
  • Jiujiu Yu
  • Sonja Körner
  • Zhi Feng Lin
  • Y Ren
  • Akihiro Nakamura
  • Michelle F Green
  • Dongning Wang
  • David Rauh
  • Jeongsoon Park
  • Lionel Sacconnay
  • Chi Chih Lai
  • Gregory R Wagner
  • Mahadevan Lakshminarasimhan
  • Firouzeh Aladini
  • Mike Schutkowski
  • Wei Zhong Zhu
  • Minjia Tan
  • Zhongyu Xie
  • H F Wang
  • Eija Pirinen
  • Yue Chen
  • Angeliki Chalkiadaki
  • Andreas S Madsen
  • Michael Van Damme
  • Bernadette M M Zwaans
  • Yingming Zhao
  • Donghui Li
  • Daniel X Tishkoff
  • Jose M Villalba
  • Quan Hao
  • Richard A Cerione
  • Y Cen
  • Nobuko Matsushita
  • Yi Qun Geng
  • Jenny Y Sun
  • Talita Carneiro Brandão Pereira
  • Yana Cen
  • Christian F W Becker
  • Kristina Schoonjans
  • Jing Yi Huang
  • Tiara L A Kawahara
  • Natalie Lefort
  • William C Hallows
  • Jason A Pfister
  • Hiroyasu Yamamoto
  • Bjoern Schwer
  • K V Chowdari
  • Johannes Trapp
  • Nidhi Ahuja
  • Anja Schuetz
  • S Kyrylenko
  • Lilia G Noriega

Detail Information

Publications70

  1. ncbi Assignment of the NAD-dependent deacetylase sirtuin 5 gene (SIRT5) to human chromosome band 6p23 by in situ hybridization
    U Mahlknecht
    Department of Hematology Oncology, University of Heidelberg Medical Center, Heidelberg, Germany
    Cytogenet Genome Res 112:208-12. 2006
    Sirtuin 5 (SIRT5) is a nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase and belongs to the Silent information regulator 2 (Sir2) family of sirtuin histone deacetylases (HDACs), which play a central role in epigenetic gene ..
  2. doi Substrates and regulation mechanisms for the human mitochondrial sirtuins Sirt3 and Sirt5
    Christine Schlicker
    Laboratory of Biochemistry, Department of Physiological Chemistry, Ruhr University Bochum, Universitaetsstrasse 150, 44801 Bochum, Germany
    J Mol Biol 382:790-801. 2008
    ..Mammalian mitochondria contain three Sirtuins, Sirt3, Sirt4, and Sirt5. Only one substrate is known for Sirt3 as well as for Sirt4, and up to now, no target for Sirt5 has been reported...
  3. doi Structural insights of SIR2rp3 proteins as promising biotargets to fight against Chagas disease and leishmaniasis
    Lionel Sacconnay
    Pharmacochemistry and Phytochemistry and Bioactive Natural Products, School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest Ansermet 30, CH 1211 Geneva 4, Switzerland
    Mol Biosyst 9:2223-30. 2013
    ..Molecular docking of known inhibitors revealed strong analogies with the mitochondrial human SIRT5 in terms of binding mode and interaction strength...
  4. doi An acetylome peptide microarray reveals specificities and deacetylation substrates for all human sirtuin isoforms
    David Rauh
    Department of Enzymology, Institute for Biochemistry and Biotechnology, Martin Luther University, Kurt Mothes Staße 3, 06120 Halle Saale, Germany
    Nat Commun 4:2327. 2013
    ..protein as a Sirt3 substrate and show that peroxiredoxin 1 and high-mobility group B1 protein are deacetylated by Sirt5 and Sirt1, respectively, at the identified sites, rendering them likely new in vivo substrates...
  5. doi SIRT5 Regulates the Mitochondrial Lysine Succinylome and Metabolic Networks
    Matthew J Rardin
    Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USA
    Cell Metab 18:920-33. 2013
    ..approach to characterize the lysine succinylome in liver mitochondria and its regulation by the desuccinylase SIRT5. A total of 1,190 unique sites were identified as succinylated, and 386 sites across 140 proteins representing ..
  6. pmc Widespread and enzyme-independent Nε-acetylation and Nε-succinylation of proteins in the chemical conditions of the mitochondrial matrix
    Gregory R Wagner
    From the Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana 46202 and
    J Biol Chem 288:29036-45. 2013
    ..These findings may have implications for the evolutionary roles that the mitochondria-localized SIRT3 deacetylase and SIRT5 desuccinylase have in the maintenance of metabolic health.
  7. pmc Oxygen flux analysis to understand the biological function of sirtuins
    Dongning Wang
    Sarah W Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, NC, USA
    Methods Mol Biol 1077:241-58. 2013
    ..Of the seven mammalian sirtuins, three localize to the mitochondria: SIRT3, SIRT4, and SIRT5. Mitochondrial sirtuins are crucial regulators of the metabolic network that controls energy homeostasis and ..
  8. pmc Ethanol metabolism modifies hepatic protein acylation in mice
    Kristofer S Fritz
    Department of Pharmaceutical Sciences, University of Colorado Denver Anschutz Medical Campus, Aurora, Colorado, United States of America
    PLoS ONE 8:e75868. 2013
    ..The newly discovered desuccinylase activity of the mitochondrial sirtuin SIRT5 suggests that protein succinylation could be an important post-translational modification regulating mitochondrial ..
  9. pmc Metabolic characterization of a Sirt5 deficient mouse model
    Jiujiu Yu
    Laboratory of Integrative and Systems Physiology LISP NCEM, School of Life Sciences, Ecole Polytechnique Federale de Lausanne EPFL, 1015 Lausanne, Switzerland
    Sci Rep 3:2806. 2013
    b>Sirt5, localized in the mitochondria, is a member of sirtuin family of NAD⁺-dependent deacetylases. Sirt5 was shown to deacetylate and activate carbamoyl phosphate synthase 1...
  10. doi Effect of breed on the expression of Sirtuins (Sirt1-7) and antioxidant capacity in porcine brain
    Y Ren
    1 Key laboratory of Animal Nutrition and Feed Science of Ministry of Agriculture, Key Laboratory of Feed and Animal Nutrition of Zhejiang Province, Institute of Feed Science, Zhejiang University, No 866 Yuhangtang Road, Hangzhou 310058, People s Republic of China
    Animal 7:1994-8. 2013
    ..the mRNA levels of Sirt1, as well as Sirt2 and Sirt4, in Jinhua pigs were greater, but the mRNA levels of Sirt3, Sirt5, Sirt6, and Sirt7 of Jinhua pigs were lower compared with Danish Landrace pigs...
  11. 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
    ..SIRT2, SIRT4 and SIRT7 were upregulated, whereas SIRT1, SIRT5 and SIRT6 were downregulated by trichostatin A (TSA) and n-butyrate...
  12. doi SIRT5 desuccinylates and activates SOD1 to eliminate ROS
    Zhi Feng Lin
    Department of Thoracic Surgery, Shanghai First People s Hospital, Shanghai Jiaotong University, Shanghai 200080, China
    Biochem Biophys Res Commun 441:191-5. 2013
    ..Here, we report that SOD1 is succinylated and that succinylation decreases its activity. SIRT5 binds to, desuccinylates and activates SOD1. SOD1-mediated ROS reduction is increased when SIRT5 is co-expressed...
  13. doi Dietary restriction increases protein acetylation in the livers of aged rats
    Akihiro Nakamura
    Department of Pediatric Cardiology and Nephrology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
    Gerontology 59:542-8. 2013
    ..Furthermore, the effects of DR on sirtuins (e.g. SIRT1, SIRT2, SIRT3, and SIRT5) have also been reported in mammals...
  14. doi Cloning, chromosomal characterization and FISH mapping of the NAD(+)-dependent histone deacetylase gene sirtuin 5 in the mouse
    Susanne Voelter-Mahlknecht
    Institute of Occupational and Social Medicine and Health Services Research, University of Tuebingen, D 72074 Tuebingen, Germany
    Int J Oncol 43:237-45. 2013
    Sirtuin 5 (SIRT5) is a nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase, belonging to the silent information regulator 2 (Sir2) family of sirtuin histone deacetylases (sirtuins)...
  15. pmc SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways
    Jeongsoon Park
    Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA
    Mol Cell 50:919-30. 2013
    Protein function is regulated by diverse posttranslational modifications. The mitochondrial sirtuin SIRT5 removes malonyl and succinyl moieties from target lysines...
  16. pmc The bicyclic intermediate structure provides insights into the desuccinylation mechanism of human sirtuin 5 (SIRT5)
    Yeyun Zhou
    MacCHESS, Cornell High Energy Synchrotron Source, Cornell University, Ithaca, New York 14853, USA
    J Biol Chem 287:28307-14. 2012
    ..Their functions have been generally attributed to NAD-dependent deacetylase activity. However, human SIRT5 (sirtuin 5), which has been reported to exhibit little deacetylase activity, was recently identified as an NAD-..
  17. ncbi Transcription levels of sirtuin family in neural stem cells and brain tissues of adult mice
    H F Wang
    Laboratory of Molecular Neurobiology, School of Life Sciences, and Institute of Systems Biology, Shanghai University, Shanghai 200444, China
    Cell Mol Biol (Noisy-le-grand) . 2012
    ..Results indicated that the expression of sirt1, sirt5 and sirt6 was significant downregulated by nicotinamide treatment...
  18. doi Mitochondrial sirtuins: regulators of protein acylation and metabolism
    Wenjuan He
    Gladstone Institute of Virology and Immunology, University of California San Francisco, San Francisco, CA 94158, USA
    Trends Endocrinol Metab 23:467-76. 2012
    ..SIRT3 deacetylates and regulates the enzymatic activity of many metabolic enzymes in mitochondria, whereas SIRT5 removes two novel post-translational modifications, lysine malonylation and succinylation...
  19. doi Synthesis of carba-NAD and the structures of its ternary complexes with SIRT3 and SIRT5
    Bruce G Szczepankiewicz
    Sirtris, a GSK Company, 200 Technology Square, Cambridge, Massachusetts 02139, USA
    J Org Chem 77:7319-29. 2012
    ..SIRT3 and SIRT5 are NAD-consuming enzymes that are potential therapeutic targets for the treatment of metabolic diseases and ..
  20. doi Differential sirtuin expression patterns in amyotrophic lateral sclerosis (ALS) postmortem tissue: neuroprotective or neurotoxic properties of sirtuins in ALS?
    Sonja Körner
    Department of Neurology, Hannover Medical School, Hannover, Germany
    Neurodegener Dis 11:141-52. 2013
    ..We assessed the expression levels of sirtuins in human postmortem ALS and control brain and spinal cord...
  21. pmc Sirtuin activators and inhibitors
    Jose M Villalba
    Departamento de Biologia Celular, Fisiologia e Inmunologia, Campus Universitario de Rabanales, Edificio Severo Ochoa, Universidad de Cordoba, Campus de Excelencia Internacional Agroalimentario, Cordoba, Spain
    Biofactors 38:349-59. 2012
    ..Sirtuin inhibitors with a wide range of core structures have been identified for SIRT1, SIRT2, SIRT3 and SIRT5 (splitomicin, sirtinol, AGK2, cambinol, suramin, tenovin, salermide, among others)...
  22. pmc A molecular mechanism for direct sirtuin activation by resveratrol
    Melanie Gertz
    Department of Biochemistry, University of Bayreuth, Bayreuth, Germany
    PLoS ONE 7:e49761. 2012
    ..Here we show that resveratrol inhibits human Sirt3 and stimulates Sirt5, in addition to Sirt1, against fluorophore-labeled peptide substrates but also against peptides and proteins ..
  23. pmc Resveratrol stimulates cortisol biosynthesis by activating SIRT-dependent deacetylation of P450scc
    Donghui Li
    Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California 92093 0704, USA
    Endocrinology 153:3258-68. 2012
    ..The effects of resveratrol on P450scc protein levels and acetylation status are dependent on SIRT3 and SIRT5 expression...
  24. pmc Sirt5 deacylation activities show differential sensitivities to nicotinamide inhibition
    Frank Fischer
    Department of Biochemistry and Research Center for Bio Macromolecules, University of Bayreuth, Bayreuth, Germany
    PLoS ONE 7:e45098. 2012
    ..Using this assay, we show that the deacetylation activity of human Sirt5 features an unusual insensitivity to nicotinamide inhibition...
  25. doi SIRT5 deacetylates and activates urate oxidase in liver mitochondria of mice
    Yasuhiko Nakamura
    Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University, Kyoto 606 8507, Japan
    FEBS Lett 586:4076-81. 2012
    We identified urate oxidase (UOX) as a target of SIRT5 by comparing mitochondrial proteins in livers of SIRT5-overexpressing transgenic (SIRT5 Tg) and wild-type mice by using two-dimensional electrophoresis...
  26. pmc Mitochondrial protein acylation and intermediary metabolism: regulation by sirtuins and implications for metabolic disease
    John C Newman
    Gladstone Institute of Virology and Immunology, San Francisco, California 94158, USA
    J Biol Chem 287:42436-43. 2012
    ..b>SIRT5 exhibits demalonylase/desuccinylase activity, and lysine succinylation and malonylation are abundant mitochondrial ..
  27. pmc HDAC isoenzyme expression is deregulated in chronic lymphocytic leukemia B-cells and has a complex prognostic significance
    Michael Van Damme
    Laboratory of Clinical Cell Therapy, Faculty of Medicine, Institut Jules Bordet, Universite Libre de Bruxelles ULB, Brussels, Belgium
    Epigenetics 7:1403-12. 2012
    ..03, p < 0.0001). For OS, SIRT5 and 6 allowed stratification into 3 groups, with a median OS of > 360, 237 and 94 mo (HR = 6.38, p < 0.0001)...
  28. pmc Mitochondrial sirtuins and metabolic homeostasis
    Eija Pirinen
    Laboratory for Integrative and Systems Physiology, School of Life Sciences, Ecole Polytechnique Federale de Lausanne, CH 1015 Lausanne, Switzerland
    Best Pract Res Clin Endocrinol Metab 26:759-70. 2012
    ..The mitochondrial sirtuins SIRT3, SIRT4 and SIRT5 together with the nuclear SIRT1 regulate several aspects of mitochondrial physiology by controlling post-..
  29. doi Inhibition of the human deacylase Sirtuin 5 by the indole GW5074
    Benjamin Suenkel
    Department of Biochemistry, University of Bayreuth, Universitaetsstrasse 30, 95447 Bayreuth, Germany
    Bioorg Med Chem Lett 23:143-6. 2013
    ..Few pharmacological inhibitors have been reported yet for human Sirt5 since substrates and assays for reliable testing of its activity were unavailable until recently, and most ..
  30. doi Identification of microRNAs regulated by isothiocyanates and association of polymorphisms inside their target sites with risk of sporadic colorectal cancer
    Ondrej Slaby
    Masaryk Memorial Cancer Institute, Department of Comprehensive Cancer Care, Brno, Czech Republic
    Nutr Cancer 65:247-54. 2013
    ..SNPs) localized within the 3'UTRs of genes (AGTR1, TNFAIP2, PRKCB, HSPA9, RABGAP1, DICER1, ADAM19, VWA5A, and SIRT5) targeted by these ITC-related miRNAs...
  31. 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 tissues (all p&..
  32. pmc Genealogy of an ancient protein family: the Sirtuins, a family of disordered members
    Susan Costantini
    Pascale Foundation National Cancer Institute Cancer Research Center CROM, via Ammiraglio Bianco, 83013, Mercogliano, Italy
    BMC Evol Biol 13:60. 2013
    ..3D structures of human SIRT2, SIRT3, and SIRT5 revealed the overall conformation of the conserved core domain but they were unable to give a structural ..
  33. pmc Thiosuccinyl peptides as Sirt5-specific inhibitors
    Bin He
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA
    J Am Chem Soc 134:1922-5. 2012
    ..Here we demonstrate that thiosuccinyl peptides are potent and selective Sirt5 inhibitors...
  34. doi Substrates for efficient fluorometric screening employing the NAD-dependent sirtuin 5 lysine deacylase (KDAC) enzyme
    Andreas S Madsen
    Department of Chemistry, Technical University of Denmark, Kemitorvet 207, DK 2800, Kongens Lyngby, Denmark
    J Med Chem 55:5582-90. 2012
    ..substrates that enable highly efficient and enzyme-economical screening employing sirtuin 5 (SIRT5)...
  35. doi Proteomic analysis of mitochondrial proteins in cardiomyocytes from rats subjected to intermittent hypoxia
    Wei Zhong Zhu
    Physiological Laboratory of Hypoxia, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, 200031 Shanghai, People s Republic of China
    Eur J Appl Physiol 112:1037-46. 2012
    ..These findings will provide clues for understanding the mechanism of IH-induced cardiac protection and may lead to the development of interventional strategies designed to utilize the advantages of IH clinically...
  36. doi Sirtuins mediate mammalian metabolic responses to nutrient availability
    Angeliki Chalkiadaki
    Paul F Glenn Laboratory, Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Building 68, Cambridge, MA 02139, USA
    Nat Rev Endocrinol 8:287-96. 2012
    ..The mitochondrial sirtuins, SIRT3, SIRT4 and SIRT5, regulate the activity of important mitochondrial enzymes and drive metabolic cycles in response to fasting and ..
  37. ncbi Structure-activity studies on suramin analogues as inhibitors of NAD+-dependent histone deacetylases (sirtuins)
    Johannes Trapp
    Institute of Pharmaceutical Sciences, Albert Ludwigs Universitat Freiburg, 79104 Freiburg, Germany
    ChemMedChem 2:1419-31. 2007
    ..The recently published X-ray crystal structure of human SIRT5 in complex with suramin and the human SIRT2 structure were used to analyze the interaction mode of the novel ..
  38. pmc Mechanism-based affinity capture of sirtuins
    Yana Cen
    Department of Pharmacology, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10065, USA
    Org Biomol Chem 9:987-93. 2011
    ..that these tools are cross reactive against a variety of human sirtuin isoforms including SIRT1, SIRT2, SIRT3, SIRT5, SIRT6 and can react with microbial derived sirtuins as well...
  39. pmc Old enzymes, new tricks: sirtuins are NAD(+)-dependent de-acylases
    Matthew D Hirschey
    Sarah W Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, NC 27710, USA
    Cell Metab 14:718-9. 2011
    ..Two new studies by Du et al. (2011) and Peng et al. (2011) identify a new enzymatic activity for SIRT5, expanding the cellular repertoire of posttranslational modifications targeted by the sirtuins.
  40. pmc Proteome profile of functional mitochondria from human skeletal muscle using one-dimensional gel electrophoresis and HPLC-ESI-MS/MS
    Natalie Lefort
    Center for Metabolic Biology, Arizona State University, Tempe, AZ, USA
    J Proteomics 72:1046-60. 2009
    ..proteins were detected, and 487 of these were assigned to the mitochondrion, including the newly characterized SIRT5, MitoNEET and RDH13...
  41. pmc SIRT5 Deacetylates carbamoyl phosphate synthetase 1 and regulates the urea cycle
    Takashi Nakagawa
    Department of Biology, Massachusetts Institute of Technology, Cambridge, 02139, USA
    Cell 137:560-70. 2009
    ..Here, we show that SIRT5 localizes in the mitochondrial matrix and interacts with carbamoyl phosphate synthetase 1 (CPS1), an enzyme, ..
  42. pmc Ure(k)a! Sirtuins Regulate Mitochondria
    William C Hallows
    Department of Biomolecular Chemistry, University of Wisconsin School of Medicine and Public Health, Madison, 53706, USA
    Cell 137:404-6. 2009
    ..In this issue, Nakagawa et al. (2009) show that the sirtuin SIRT5 deacetylates and activates a mitochondrial enzyme, carbamoyl phosphate synthetase 1, which mediates the first step ..
  43. pmc SIRT6 links histone H3 lysine 9 deacetylation to NF-kappaB-dependent gene expression and organismal life span
    Tiara L A Kawahara
    Program in Epithelial Biology, Division of Endocrinology, Gerontology, and Metabolism, Stanford University School of Medicine, Stanford, CA 94305, USA
    Cell 136:62-74. 2009
    ..We propose that SIRT6 attenuates NF-kappaB signaling via H3K9 deacetylation at chromatin, and hyperactive NF-kappaB signaling may contribute to premature and normal aging...
  44. 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. The effect of SIRTs 3-7 on the regulation of neuronal survival, if any, has yet to be reported...
  45. doi Alcohol alters hepatic FoxO1, p53, and mitochondrial SIRT5 deacetylation function
    Charles S Lieber
    Section of Liver Disease and Nutrition, James J Peters VA Medical Center, 130 West Kingsbridge Road 151 2, Bronx, NY 10468, USA
    Biochem Biophys Res Commun 373:246-52. 2008
    ..04 and p=0.02, respectively) while hepatic p53 was found hyperacetylated (p=0.017). Furthermore, mitochondrial SIRT5 was reduced (p=0.0025), and PGC-1alpha hyperacetylated (p=0.027), establishing their role in protein modification...
  46. ncbi Localization of mouse mitochondrial SIRT proteins: shift of SIRT3 to nucleus by co-expression with SIRT5
    Yasuhiko Nakamura
    Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University, 54 Kawahara cho, Shogoin, Sakyo ku, Kyoto 606 8507, Japan
    Biochem Biophys Res Commun 366:174-9. 2008
    ..regulator 2 (SIR2) is involved in extension of yeast longevity by calorie restriction, and SIRT3, SIRT4, and SIRT5 are mammalian homologs of SIR2 localized in mitochondria...
  47. 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
    ..no mitochondrial hyperacetylation was detectable in mice lacking the two other mitochondrial sirtuins, SIRT4 and SIRT5. Surprisingly, despite this biochemical phenotype, SIRT3-deficient mice are metabolically unremarkable under basal ..
  48. ncbi Regulation of insulin secretion by SIRT4, a mitochondrial ADP-ribosyltransferase
    Nidhi Ahuja
    Gladstone Institute of Virology and Immunology, University of California, San Francisco, California 94158, USA
    J Biol Chem 282:33583-92. 2007
    ..Depletion of SIRT4 from insulin-producing INS-1E cells results in increased insulin secretion in response to glucose. These observations define a new role for mitochondrial SIRT4 in the regulation of insulin secretion...
  49. ncbi Sirtuin functions in health and disease
    Hiroyasu Yamamoto
    Institut de Genetique et de Biologie Moleculaire et Cellulaire, 1 rue Laurent Fries, Boite Postale 10142, 67404 Illkirch, France
    Mol Endocrinol 21:1745-55. 2007
    ..Here, we review some of the recent data related to the sirtuins and discuss their mode of action, their biological role in cellular and organismal models, and their possible association to age-related human diseases...
  50. ncbi Structural basis of inhibition of the human NAD+-dependent deacetylase SIRT5 by suramin
    Anja Schuetz
    Structural Genomics Consortium, University of Toronto, 100 College Street, Toronto, Ontario M5G 1L5, Canada
    Structure 15:377-89. 2007
    ..We identified suramin as a compound that binds to human SIRT5 and showed that it inhibits SIRT5 NAD(+)-dependent deacetylase activity with an IC(50) value of 22 microM...
  51. ncbi DNA pooling: a comprehensive, multi-stage association analysis of ACSL6 and SIRT5 polymorphisms in schizophrenia
    K V Chowdari
    Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15213, USA
    Genes Brain Behav 6:229-39. 2007
    ..and two positional candidate genes: ACSL6 (Acyl-Coenzyme A synthetase long-chain family member 6) and SIRT5 (silent mating type information regulation 2 homologue 5)...
  52. pmc Evolutionarily conserved and nonconserved cellular localizations and functions of human SIRT proteins
    Eriko Michishita
    Laboratory of Biosystems and Cancer, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Mol Biol Cell 16:4623-35. 2005
    ..with heterochromatic regions and nucleoli, respectively, where yeast Sir2 functions; 2) SIRT3, SIRT4, and SIRT5 are localized in mitochondria, an organelle that links aging and energy metabolism; 3) cellular p53 is a major in ..
  53. 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.
  54. doi Function and regulation of the mitochondrial sirtuin isoform Sirt5 in Mammalia
    Melanie Gertz
    Department of Physiological Chemistry, Ruhr University Bochum, Bochum, Germany
    Biochim Biophys Acta 1804:1658-65. 2010
    ..Mammals have seven Sirtuin isoforms, three of them - Sirt3, Sirt4, and Sirt5 - located to mitochondria, our centers of energy metabolism and apoptosis initiation...
  55. doi Mitochondrial sirtuins
    Jing Yi Huang
    Gladstone Institute of Virology and Immunology, University of California, San Francisco, CA, USA
    Biochim Biophys Acta 1804:1645-51. 2010
    ..Three sirtuins, SIRT3, 4 and 5, are located within the mitochondrial matrix. SIRT3 and SIRT5 are NAD(+)-dependent deacetylases that remove acetyl groups from acetyllysine-modified proteins and yield 2'-O-..
  56. pmc Sirt5 is a NAD-dependent protein lysine demalonylase and desuccinylase
    Jintang Du
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA
    Science 334:806-9. 2011
    ..Four of them (Sirt4 to Sirt7) have no detectable or very weak deacetylase activity. We found that Sirt5 is an efficient protein lysine desuccinylase and demalonylase in vitro...
  57. pmc The first identification of lysine malonylation substrates and its regulatory enzyme
    Chao Peng
    Ben May Department for Cancer Research, The University of Chicago, Chicago, IL 60637, USA
    Mol Cell Proteomics 10:M111.012658. 2011
    ..In addition, we demonstrate that Sirt5, a member of the class III lysine deacetylases, can catalyze lysine demalonylation and lysine desuccinylation ..
  58. pmc Mitochondrial sirtuins in the regulation of mitochondrial activity and metabolic adaptation
    David B Lombard
    Department of Pathology, Institute of Gerontology, 3015 BSRB, Ann Arbor, MI 48109, USA
    Handb Exp Pharmacol 206:163-88. 2011
    ..In mammals, three members of the sirtuin class of NAD(+)-dependent deacetylases - SIRT3, SIRT4, and SIRT5 - localize to mitochondria and regulate targets involved in a diverse array of biochemical pathways...
  59. doi SIRT1 and SIRT5 activity expression and behavioral responses to calorie restriction
    Yi Qun Geng
    Central Laboratory, Shantou University and The Chinese University of Hong Kong Joint Shantou International Eye Center, Shantou, Guangdong 515041, China
    J Cell Biochem 112:3755-61. 2011
    To investigate the effects of calorie restriction (CR) on behavioral performance and expression of SIRT1 and SIRT5 in rat cerebral tissues...
  60. pmc Mammalian sirtuins and energy metabolism
    Xiaoling Li
    Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
    Int J Biol Sci 7:575-87. 2011
    ..This review focuses on the involvement of two nuclear sirtuins, SIRT1 and SIRT6, and three mitochondrial sirtuins, SIRT3, SIRT4, and SIRT5, in regulation of diverse metabolic processes.
  61. ncbi Advances in characterization of human sirtuin isoforms: chemistries, targets and therapeutic applications
    Y Cen
    Department of Pharmacology, Weill Medical College of Cornell University, New York, NY 10065, USA
    Curr Med Chem 18:1919-35. 2011
    ..There are seven human sirtuin isoforms called SIRT1-SIRT7. The biochemical functions of SIRT1, SIRT2, SIRT3, SIRT5 and SIRT6 have been reported and NAD+ dependent deacetylase activities confirmed...
  62. doi Histone deacetylase inhibitors demonstrate significant preclinical activity as single agents, and in combination with bortezomib in Waldenström's macroglobulinemia
    Jenny Y Sun
    Bing Center for Waldenstrom s Macroglobulinemia, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Clin Lymphoma Myeloma Leuk 11:152-6. 2011
    ..of bone marrow CD19+ cells from 30 patients and 10 healthy donors showed overexpression of HDAC4, HDAC9, and Sirt5, with validation of HDAC9 overexpression by q-PCR in primary and BCWM.1 cells...
  63. doi Zebrafish as a model organism to evaluate drugs potentially able to modulate sirtuin expression
    Talita Carneiro Brandão Pereira
    Laboratório de Biologia Genômica e Molecular, Departamento de Biologia Celular e Molecular, Faculdade de Biociencias, Pontificia Universidade Catolica do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
    Zebrafish 8:9-16. 2011
    ..SIRT1, SIRT3, SIRT5, and SIRT6 genes were expressed in all tissues, and SIRT1 exhibited the highest level of expression in all organs...
  64. doi Distinct regulation of mitochondrial localization and stability of two human Sirt5 isoforms
    Nobuko Matsushita
    Laboratory of Molecular Biochemistry, School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192 0392, Japan
    Genes Cells 16:190-202. 2011
    ..In this study, we clarified the mechanism of subcellular localization of two SIRT5 isoforms (i.e...
  65. doi The proteomic response of the mussel congeners Mytilus galloprovincialis and M. trossulus to acute heat stress: implications for thermal tolerance limits and metabolic costs of thermal stress
    Lars Tomanek
    California Polytechnic State University, Department of Biological Sciences, Center for Coastal Marine Sciences, Environmental Proteomics Laboratory, 1 Grand Avenue, San Luis Obispo, CA 93407 0401, USA
    J Exp Biol 213:3559-74. 2010
    ..galloprovincialis, which is consistent with its expanding range in warmer waters...
  66. pmc Brain molecular aging, promotion of neurological disease and modulation by sirtuin 5 longevity gene polymorphism
    Christin Glorioso
    Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15213, USA
    Neurobiol Dis 41:279-90. 2011
    ..that subjects carrying a newly-characterized low-expressing polymorphism in a putative longevity gene (Sirtuin5; SIRT5(prom2)) have older brain molecular ages...
  67. pmc Sirtuin regulation of mitochondria: energy production, apoptosis, and signaling
    Eric Verdin
    Gladstone Institute of Virology and Immunology, San Francisco, CA 94158, USA
    Trends Biochem Sci 35:669-75. 2010
    ..Three sirtuins, SIRT3, SIRT4 and SIRT5, are located in the mitochondria, dynamic organelles that function as the primary site of oxidative metabolism and ..
  68. pmc Urea cycle regulation by mitochondrial sirtuin, SIRT5
    Takashi Nakagawa
    Paul F Glenn Laboratory for the Science of Aging and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Aging (Albany NY) 1:578-81. 2009
    Mammalian sirtuins have diverse roles in aging, metabolism and disease. Recently we reported a new function for SIRT5 in urea cycle regulation...
  69. doi Overexpression of SIRT5 confirms its involvement in deacetylation and activation of carbamoyl phosphate synthetase 1
    Masahito Ogura
    Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University, Shogoin, Sakyo ku, Kyoto 606 8507, Japan
    Biochem Biophys Res Commun 393:73-8. 2010
    ..In mammals, among the seven SIR2 homologues (SIRT1-7), SIRT3, 4, and 5 are localized to mitochondria. As SIRT5 mRNA levels in liver are increased by fasting, the physiological role of SIRT5 was investigated in liver of SIRT5-..
  70. 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
    ..The SIRT1 sequence has the closest homology to the S. cerevisiae Sir2p. The SIRT4 and SIRT5 sirtuins more closely resemble prokaryotic sirtuin sequences...

Research Grants55

  1. Regulation of HIV transcription and replication by SDF-1gamma
    Eric Verdin; Fiscal Year: 2006
    ..We will determine whether a correlations exist between SDF-1gamma expression, HIV replication and the presence of the SDF1-3'A allele. ..
  2. A New In Vitro Model for HIV Latency
    Eric Verdin; Fiscal Year: 2004
    ..These studies should further establish the validity of our model for the study of HIV latency in patients. ..
  3. DLPC Treatment of Alcoholic and Non-Alcoholic Fibrosis
    Charles Lieber; Fiscal Year: 2006
    ..abstract_text> ..
  4. ANTIVIRAL & ANTIFIBROTIC LIVER THERAPY OF HCV+ DRINKERS
    Charles Lieber; Fiscal Year: 2005
    ..Funds are requested for special laboratory tests, study nurses, travel to meetings, patient monitoring expenses and a core office. ..
  5. Epigenetic regulation of HIV latency
    ERIC M VERDIN; Fiscal Year: 2010
    ..Here we propose to study the role of epigenetic modifications in HIV latency and the possible role of drugs that modify epigenetic silencing as a novel therapeutic approach to induce the reactivation of latent HIV. ..
  6. ROLE OF CHROMATIN IN HIV TRANSCRIPTIONAL REGULATION
    ERIC M VERDIN; Fiscal Year: 2010
    ..These experiments have the potential of identifying novel factors mediating HIV transcriptional regulation that could be targeted therapeutically in the future. ..
  7. ROLE OF CHROMATIN IN HIV TRANSCRIPTIONAL REGULATION
    Eric Verdin; Fiscal Year: 2007
    ..These experiments have the potential of identifying novel factors mediating HIV transcriptional regulation that could be targeted therapeutically in the future. ..
  8. Synergistic Nutraceutical Effects of DLPC and SAMe
    Charles Lieber; Fiscal Year: 2007
    ....
  9. Antiviral/Antifibrotic Liver Therapy of Hepatitis C positive Alcohol Drinkers
    Charles Lieber; Fiscal Year: 2007
    ..Accordingly, support is requested for the completion of this novel approach for the treatment of HCV+ patients who become abstinent or who continue to consume alcohol moderately. ..
  10. Liver Fibrosis, Inflammation & Oxidative Stress Markers
    Charles Lieber; Fiscal Year: 2006
    ..abstract_text> ..
  11. MODULATION OF CD8 T CELL FUNCTION BY HIV ENVELOPE PROTEI
    Eric Verdin; Fiscal Year: 2003
    ..abstract_text> ..
  12. ROLE OF CHROMATIN IN HIV TRANSCRIPTIONAL REGULATION
    Eric Verdin; Fiscal Year: 2003
    ..Finally, the applicant will use an in vitro transcription system reconstituted with purified histones to evaluate the effects of specific mutations in the histone amino tails (sites of acetylation) on HIV expression. ..
  13. INTERACTION OF ETHANOL WITH HEPATIC MICROSOMES
    Charles Lieber; Fiscal Year: 1992
    ..Our ultimate goal is to define in molecular terms some of the most far-reaching changes brought about by chronic ethanol consumption in the internal milieu of the body and the resulting response to the environment...
  14. DLPC TREATMENT OF ALCOHOLIC AND NON ALCOHOLIC FIBROSIS
    Charles Lieber; Fiscal Year: 2000
    ..If successful, the proposed studies will establish DLPC as the first safe and chemically defined agent capable of preventing the progression (and possibly of promoting the regression) of hepatic and pulmonary fibrosis. ..
  15. MECHANISM AND ROLE OF MICROSOMAL ETHANOL OXIDATION
    Charles Lieber; Fiscal Year: 2001
    ..Such information is aimed at elucidating key aspects of alcohol mediated pathology in a way which may eventually affect alcohol related medical complications, their prevention and treatment. ..
  16. MODULATION OF T CELL FUNCTIONS BY HIV1 TAT
    Eric Verdin; Fiscal Year: 2001
    ..These studies will further define the role of Tat as modulator of T cell differentiated functions and establish its role in HIV pathogenesis. ..