Research Topics
Genomes and Genes
| Raul MostoslavskySummaryAffiliation: Harvard University Country: USA Publications
Research Grants
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Detail Information
Publications
DNA repair, insulin signaling and sirtuins: at the crossroads between cancer and agingRaul Mostoslavsky
Department of Medicine, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA
Front Biosci 13:6966-90. 2008....- At the crossroad of lifespan, calorie restriction, chromatin and disease: meeting on sirtuinsRaul 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... - Genomic instability and aging-like phenotype in the absence of mammalian SIRT6Raul 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... - Mammalian SIRT1 limits replicative life span in response to chronic genotoxic stressKatrin 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... 
The histone deacetylase SIRT6 is a tumor suppressor that controls cancer metabolismCarlos 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...- DNA repair, genome stability, and agingDavid 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... - Mammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylationDavid 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... - SIRT1 redistribution on chromatin promotes genomic stability but alters gene expression during agingPhilipp 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... - Metabolic control of muscle mitochondrial function and fatty acid oxidation through SIRT1/PGC-1alphaZachary 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... - SIRT6: a master epigenetic gatekeeper of glucose metabolismLei 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... - Chromatin protein L3MBTL1 is dispensable for development and tumor suppression in miceJinzhong 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... - The deacetylase Sirt6 activates the acetyltransferase GCN5 and suppresses hepatic gluconeogenesisJohn 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... - Conserved role of SIRT1 orthologs in fasting-dependent inhibition of the lipid/cholesterol regulator SREBPAmy 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... - SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic beta cellsMarcia 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... - Fine tuning our cellular factories: sirtuins in mitochondrial biologyLei 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... - Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylaseAnne 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... - A SIRT1-LSD1 corepressor complex regulates Notch target gene expression and developmentPeter 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... - From sirtuin biology to human diseases: an updateCarlos 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... 
Characterization of nuclear sirtuins: molecular mechanisms and physiological relevanceDebra 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...- The lingering enigma of the allelic exclusion mechanismRaul 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... - The histone deacetylase Sirt6 regulates glucose homeostasis via Hif1alphaLei 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... - Mechanism and control of V(D)J recombination at the immunoglobulin heavy chain locusDavid 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... - 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)... - Developmental defects and p53 hyperacetylation in Sir2 homolog (SIRT1)-deficient miceHwei 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... - 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... - Chromatin dynamics and locus accessibility in the immune systemRaul 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... - Allelic 'choice' governs somatic hypermutation in vivo at the immunoglobulin kappa-chain locusShira 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... - SIRT1 regulates circadian clock gene expression through PER2 deacetylationGad 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... - Sirtuin-mediated deacetylation pathway stabilizes Werner syndrome proteinTomoaki 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:.. - A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagyIn 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... - SIRT1 controls endothelial angiogenic functions during vascular growthMichael 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...
Research Grants
- The histone deacetylase SIRT6 functions as a co-repressor of Hif1 alpha in glucosRaul Mostoslavsky; Fiscal Year: 2010....
- Mammalian SIRT6 Is A Master Regulator Of Glucose HomeostasisRaul Mostoslavsky; Fiscal Year: 2010....