Raul Mostoslavsky

Summary

Affiliation: Harvard University
Country: USA

Publications

  1. pmc Sirtuins, metabolism, and cancer
    Barbara Martinez-Pastor
    The Massachusetts General Hospital, Cancer Center Harvard Medical School Boston, MA, USA
    Front Pharmacol 3:22. 2012
  2. ncbi request reprint The histone deacetylase SIRT6: at the crossroads between epigenetics, metabolism and disease
    Jean Pierre Etchegaray
    The Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA
    Curr Top Med Chem 13:2991-3000. 2013
  3. ncbi request reprint DNA repair, insulin signaling and sirtuins: at the crossroads between cancer and aging
    Raul Mostoslavsky
    Department of Medicine, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA
    Front Biosci 13:6966-90. 2008
  4. ncbi request reprint At the crossroad of lifespan, calorie restriction, chromatin and disease: meeting on sirtuins
    Raul Mostoslavsky
    Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA, USA
    Cell Cycle 9:1907-12. 2010
  5. pmc SIRT6 recruits SNF2H to DNA break sites, preventing genomic instability through chromatin remodeling
    Debra Toiber
    The Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA
    Mol Cell 51:454-68. 2013
  6. ncbi request reprint Genomic instability and aging-like phenotype in the absence of mammalian SIRT6
    Raul Mostoslavsky
    Howard Hughes Medical Institute, The Children s Hospital, CBR Institute for Biomedical Research, Harvard University Medical School, Boston, MA 02115, USA
    Cell 124:315-29. 2006
  7. ncbi request reprint Mammalian SIRT1 limits replicative life span in response to chronic genotoxic stress
    Katrin F Chua
    Howard Hughes Medical Institute, Children s Hospital, CBR Institute for Biomedical Research, Department of Genetics, Harvard University Medical School, Boston, MA 02115, USA
    Cell Metab 2:67-76. 2005
  8. doi request reprint Assaying chromatin sirtuins
    Lei Zhong
    The Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA
    Methods Mol Biol 1077:149-63. 2013
  9. pmc The histone deacetylase SIRT6 is a tumor suppressor that controls cancer metabolism
    Carlos Sebastian
    The Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA
    Cell 151:1185-99. 2012
  10. ncbi request reprint DNA repair, genome stability, and aging
    David B Lombard
    Howard Hughes Medical Institute, The Children s Hospital, Department of Genetics, Harvard Medical School and, The CBR Institute for Biomedical Research, Boston, Massachusetts 02115, USA
    Cell 120:497-512. 2005

Detail Information

Publications41

  1. pmc Sirtuins, metabolism, and cancer
    Barbara Martinez-Pastor
    The Massachusetts General Hospital, Cancer Center Harvard Medical School Boston, MA, USA
    Front Pharmacol 3:22. 2012
    ..Here, we specifically review recent progress on the role of sirtuins in DNA repair and energy metabolism, further discussing the implication of sirtuins in the biology of cancer...
  2. ncbi request reprint The histone deacetylase SIRT6: at the crossroads between epigenetics, metabolism and disease
    Jean Pierre Etchegaray
    The Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA
    Curr Top Med Chem 13:2991-3000. 2013
    ..This review describes the most current information regarding the molecular and physiological relevance of SIRT6 in the context of epigenetics, metabolism and disease. ..
  3. ncbi request reprint DNA repair, insulin signaling and sirtuins: at the crossroads between cancer and aging
    Raul Mostoslavsky
    Department of Medicine, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA
    Front Biosci 13:6966-90. 2008
    ....
  4. ncbi request reprint At the crossroad of lifespan, calorie restriction, chromatin and disease: meeting on sirtuins
    Raul Mostoslavsky
    Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA, USA
    Cell Cycle 9:1907-12. 2010
    ..Undoubtedly, this is an increasingly expanding field that it is here to stay and growth...
  5. pmc SIRT6 recruits SNF2H to DNA break sites, preventing genomic instability through chromatin remodeling
    Debra Toiber
    The Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA
    Mol Cell 51:454-68. 2013
    ..We present a unique crosstalk between a histone modifier and a chromatin remodeler, regulating a coordinated response to prevent DNA damage. ..
  6. ncbi request reprint Genomic instability and aging-like phenotype in the absence of mammalian SIRT6
    Raul Mostoslavsky
    Howard Hughes Medical Institute, The Children s Hospital, CBR Institute for Biomedical Research, Harvard University Medical School, Boston, MA 02115, USA
    Cell 124:315-29. 2006
    ..We conclude that one function of SIRT6 is to promote normal DNA repair, and that SIRT6 loss leads to abnormalities in mice that overlap with aging-associated degenerative processes...
  7. ncbi request reprint Mammalian SIRT1 limits replicative life span in response to chronic genotoxic stress
    Katrin F Chua
    Howard Hughes Medical Institute, Children s Hospital, CBR Institute for Biomedical Research, Department of Genetics, Harvard University Medical School, Boston, MA 02115, USA
    Cell Metab 2:67-76. 2005
    ..Together, our findings demonstrate an unexpected SIRT1 function in promoting replicative senescence in response to chronic cellular stress and implicate p19(ARF) as a downstream effector in this pathway...
  8. doi request reprint Assaying chromatin sirtuins
    Lei Zhong
    The Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA
    Methods Mol Biol 1077:149-63. 2013
    ....
  9. pmc The histone deacetylase SIRT6 is a tumor suppressor that controls cancer metabolism
    Carlos Sebastian
    The Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA
    Cell 151:1185-99. 2012
    ..Our studies reveal SIRT6 to be a potent tumor suppressor acting to suppress cancer metabolism...
  10. ncbi request reprint DNA repair, genome stability, and aging
    David B Lombard
    Howard Hughes Medical Institute, The Children s Hospital, Department of Genetics, Harvard Medical School and, The CBR Institute for Biomedical Research, Boston, Massachusetts 02115, USA
    Cell 120:497-512. 2005
    ..We review Sir2, a factor linking genomic stability, metabolism, and aging. We conclude with a general discussion of the role of mutant mice in aging research and avenues for future investigation...
  11. 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
    ..Overall, our results extend the recent finding of lysine acetylation of mitochondrial proteins and demonstrate that SIRT3 has evolved to control reversible lysine acetylation in this organelle...
  12. pmc Metabolic control of muscle mitochondrial function and fatty acid oxidation through SIRT1/PGC-1alpha
    Zachary Gerhart-Hines
    Dana Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, One Jimmy Fund Way, Boston, MA 02115, USA
    EMBO J 26:1913-23. 2007
    ..These results have implications for understanding selective nutrient adaptation and how it might impact lifespan or metabolic diseases such as obesity and diabetes...
  13. pmc SIRT1 redistribution on chromatin promotes genomic stability but alters gene expression during aging
    Philipp Oberdoerffer
    Department of Pathology and Glenn Labs for Aging Research, Harvard Medical School, Boston, MA 02115, USA
    Cell 135:907-18. 2008
    ..Thus, DNA damage-induced redistribution of SIRT1 and other chromatin-modifying proteins may be a conserved mechanism of aging in eukaryotes...
  14. pmc Chromatin and beyond: the multitasking roles for SIRT6
    Sita Kugel
    Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA
    Trends Biochem Sci 39:72-81. 2014
    ..In this article we seek to describe and expand this knowledge with recent advances in understanding the mechanisms of SIRT6 action and their implications for human biology and disease. ..
  15. pmc The deacetylase Sirt6 activates the acetyltransferase GCN5 and suppresses hepatic gluconeogenesis
    John E Dominy
    Department of Cancer Biology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Mol Cell 48:900-13. 2012
    ..Activation of hepatic Sirt6 may therefore be therapeutically useful for treating insulin-resistant diabetes...
  16. pmc SIRT6: a master epigenetic gatekeeper of glucose metabolism
    Lei Zhong
    Massachusetts General Hospital Cancer Center, Boston, USA
    Transcription 1:17-21. 2010
    ..In this Point of View article, we will first highlight our recent findings, and then provide an in-depth discussion of their implications in cancer and aging...
  17. pmc Chromatin protein L3MBTL1 is dispensable for development and tumor suppression in mice
    Jinzhong Qin
    Cancer Center, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
    J Biol Chem 285:27767-75. 2010
    ..In cohorts of mice followed for more than 2 years, lack of L3MBTL1 did not alter normal lifespan or survival with or without sublethal irradiation...
  18. pmc Metabolism, longevity and epigenetics
    Claudia Cosentino
    The Massachusetts General Hospital Cancer Center Harvard Medical School, 185 Cambridge St, Boston, MA, USA
    Cell Mol Life Sci 70:1525-41. 2013
    ..We summarize current knowledge of the emerging concepts indicating close crosstalk between the epigenetic machineries able to sense metabolic stress, their adaptive metabolic responses and their potential role in longevity...
  19. pmc Conserved role of SIRT1 orthologs in fasting-dependent inhibition of the lipid/cholesterol regulator SREBP
    Amy K Walker
    Massachusetts General Hospital Cancer Center, Charlestown, Massachusetts 02129, USA
    Genes Dev 24:1403-17. 2010
    ..These findings may have important biomedical implications for the treatment of metabolic disorders associated with aberrant lipid/cholesterol homeostasis, including metabolic syndrome and atherosclerosis...
  20. pmc Fine tuning our cellular factories: sirtuins in mitochondrial biology
    Lei Zhong
    The Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA
    Cell Metab 13:621-6. 2011
    ..Here, we review recent advances on the role of this fascinating family of mammalian proteins and their well-orchestrated function in modulating mitochondrial activity...
  21. ncbi request reprint SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic beta cells
    Marcia C Haigis
    Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA
    Cell 126:941-54. 2006
    ..These results indicate that SIRT4 functions in beta cell mitochondria to repress the activity of GDH by ADP-ribosylation, thereby downregulating insulin secretion in response to amino acids, effects that are alleviated during CR...
  22. pmc A tale of metabolites: the cross-talk between chromatin and energy metabolism
    Barbara Martinez-Pastor
    The Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA
    Cancer Discov 3:497-501. 2013
    ....
  23. pmc A SIRT1-LSD1 corepressor complex regulates Notch target gene expression and development
    Peter Mulligan
    Massachusetts General Hospital Cancer Center and Harvard Medical School, Building 149, 13th Street, Charlestown, MA 02129, USA
    Mol Cell 42:689-99. 2011
    ..These findings offer new insights into conserved mechanisms of epigenetic gene repression and regulation of development by SIRT1 in metazoans...
  24. ncbi request reprint Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase
    Anne Brunet
    Division of Neuroscience, Children s Hospital, and Department of Neurobiology, Center for Blood Research CBR Institute for Biomedical Research, Harvard Medical School, Boston, MA 02115, USA
    Science 303:2011-5. 2004
    ..Thus, one way in which members of the Sir2 family of proteins may increase organismal longevity is by tipping FOXO-dependent responses away from apoptosis and toward stress resistance...
  25. pmc The histone deacetylase Sirt6 regulates glucose homeostasis via Hif1alpha
    Lei Zhong
    The Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA
    Cell 140:280-93. 2010
    ..Our studies uncover a role for the chromatin factor SIRT6 as a master regulator of glucose homeostasis and may provide the basis for novel therapeutic approaches against metabolic diseases, such as diabetes and obesity...
  26. pmc From sirtuin biology to human diseases: an update
    Carlos Sebastian
    Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts 02114, USA
    J Biol Chem 287:42444-52. 2012
    ..In this minireview, we provide an update on the known roles for each of the seven mammalian sirtuins in these areas...
  27. doi request reprint Characterization of nuclear sirtuins: molecular mechanisms and physiological relevance
    Debra Toiber
    The Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA
    Handb Exp Pharmacol 206:189-224. 2011
    ..In this chapter, we summarize current concepts on non-metabolic functions for sirtuins, depicting this broad family from yeast to mammals...
  28. ncbi request reprint Mechanism and control of V(D)J recombination at the immunoglobulin heavy chain locus
    David Jung
    Howard Hughes Medical Institute, Children s Hospital, CBR Institute for Biomedical Research, and Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA
    Annu Rev Immunol 24:541-70. 2006
    ..In this review, we summarize advances that have been made in understanding how V(D)J recombination at the IgH locus is controlled and discuss important areas for future investigation...
  29. ncbi request reprint The lingering enigma of the allelic exclusion mechanism
    Raul Mostoslavsky
    Howard Hughes Medical Institute, The Children s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Cell 118:539-44. 2004
    ..Despite some progress, the precise mechanism of allelic exclusion remains an enigma...
  30. pmc SIRT6 Is Required for Normal Retinal Function
    Dafne M Silberman
    Laboratory of Retinal Neurochemistry and Experimental Ophthalmology, Department of Human Biochemistry, School of Medicine, CEFYBO CONICET UBA, Buenos Aires, Argentina Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts, United States of America
    PLoS ONE 9:e98831. 2014
    ..Our results identify SIRT6 as a critical modulator of retinal function, likely through its effects on chromatin. ..
  31. doi request reprint eNERgizing pluripotent gene transcription
    Jean Pierre Etchegaray
    The Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, USA
    Cell Stem Cell 9:285-6. 2011
    ....
  32. ncbi request reprint SIRT3 in calorie restriction: can you hear me now?
    Carlos Sebastian
    The Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, 02114, USA
    Cell 143:667-8. 2010
    ..2010) show that the sirtuin SIRT3 mediates the protective effects of caloric restriction on age-related hearing loss by promoting the mitochondrial antioxidant system through the regulation of isocitrate dehydrogenase 2 (Idh2)...
  33. ncbi request reprint Receptor revision in T cells: an open question?
    Raul Mostoslavsky
    Howard Hughes Medical Institute, The Children s Hospital, The Center for Blood Research, and Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
    Trends Immunol 25:276-9. 2004
    ..Although the existence of such a process in T cells remains controversial, recent studies suggest that mature T cells are able to similarly revise their receptors in the periphery...
  34. pmc Developmental defects and p53 hyperacetylation in Sir2 homolog (SIRT1)-deficient mice
    Hwei Ling Cheng
    Howard Hughes Medical Institute, Children s Hospital, Center for Blood Research, and Department of Genetics, Harvard University Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 100:10794-9. 2003
    ..Together, our observations provide direct evidence that endogenous SIRT1 protein regulates p53 acetylation and p53-dependent apoptosis, and show that the function of this enzyme is required for specific developmental processes...
  35. ncbi request reprint Chromatin dynamics and locus accessibility in the immune system
    Raul Mostoslavsky
    Howard Hughes Medical Institute, Children s Hospital, Center for Blood Research, and Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nat Immunol 4:603-6. 2003
    ..Moreover, once a cell becomes terminally differentiated, 'heritable' gene expression must be maintained in all daughter cells and, thus, faithfully recapitulated after each cellular division...
  36. ncbi request reprint Allelic 'choice' governs somatic hypermutation in vivo at the immunoglobulin kappa-chain locus
    Shira Fraenkel
    The Hebrew University Hadassah Medical School, Jerusalem 91120, Israel
    Nat Immunol 8:715-22. 2007
    ..Thus, it seems that the epigenetic mechanisms that initially bring about monoallelic variable-(diversity)-joining rearrangement continue to be involved in the control of antibody diversity at later stages of B cell development...
  37. pmc SIRT1 controls endothelial angiogenic functions during vascular growth
    Michael Potente
    Molecular Cardiology, Department of Internal Medicine III, University of Frankfurt, 60590 Frankfurt, Germany
    Genes Dev 21:2644-58. 2007
    ..These findings uncover a novel and unexpected role for SIRT1 as a critical modulator of endothelial gene expression governing postnatal vascular growth...
  38. doi request reprint Sirtuin-mediated deacetylation pathway stabilizes Werner syndrome protein
    Tomoaki Kahyo
    Molecular Gerontology Research Group, Mitsubishi Kagaku Institute of Life Sciences, Minamiooya, Machida, Tokyo, Japan
    FEBS Lett 582:2479-83. 2008
    ..Furthermore, we found a decrease in the WRN level in Sirt1-deficient mice. These results indicate that sirtuin-mediated deacetylation stabilizes WRN. STRUCTURED SUMMARY:..
  39. doi request reprint SIRT1 regulates circadian clock gene expression through PER2 deacetylation
    Gad Asher
    Department of Molecular Biology, Sciences III, University of Geneva, 30, Quai Ernest Ansermet, CH 1211 Geneva 4, Switzerland
    Cell 134:317-28. 2008
    ..Given the NAD(+) dependence of SIRT1 deacetylase activity, it is likely that SIRT1 connects cellular metabolism to the circadian core clockwork circuitry...
  40. pmc A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy
    In Hye Lee
    Translational Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892
    Proc Natl Acad Sci U S A 105:3374-9. 2008
    ..These results suggest that the Sirt1 deacetylase is an important in vivo regulator of autophagy and provide a link between sirtuin function and the overall cellular response to limited nutrients...

Research Grants2