histone deacetylases

Summary

Summary: Deacetylases that remove N-acetyl groups from amino side chains of the amino acids of HISTONES. Some of these belong to the SIRTUINS protein family.

Top Publications

  1. doi Lysine acetylation targets protein complexes and co-regulates major cellular functions
    Chunaram Choudhary
    Proteomics and Signal Transduction, Max Planck Institute for Biochemistry, Martinsried, Germany
    Science 325:834-40. 2009
  2. ncbi Anticancer activities of histone deacetylase inhibitors
    Jessica E Bolden
    Cancer Immunology Program, Peter MacCallum Cancer Centre, St Andrews Place, East Melbourne 3002, Victoria, Australia
    Nat Rev Drug Discov 5:769-84. 2006
  3. ncbi Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase
    S Imai
    Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA
    Nature 403:795-800. 2000
  4. pmc HDAC2 negatively regulates memory formation and synaptic plasticity
    Ji Song Guan
    Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences
    Nature 459:55-60. 2009
  5. ncbi HDAC6 rescues neurodegeneration and provides an essential link between autophagy and the UPS
    Udai Bhan Pandey
    Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Nature 447:859-63. 2007
  6. pmc Histone deacetylases (HDACs): characterization of the classical HDAC family
    Annemieke J M de Ruijter
    Academic Medical Centre, University of Amsterdam, Amsterdam, The, Netherlands
    Biochem J 370:737-49. 2003
  7. ncbi The deacetylase HDAC6 regulates aggresome formation and cell viability in response to misfolded protein stress
    Yoshiharu Kawaguchi
    Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA
    Cell 115:727-38. 2003
  8. ncbi Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer
    Saverio Minucci
    Department of Experimental Oncology, European Institute of Oncology, Via Ripamanti 435, 20141, Milan, Italy
    Nat Rev Cancer 6:38-51. 2006
  9. ncbi Histone deacetylase inhibitors: molecular mechanisms of action
    W S Xu
    Cell Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Oncogene 26:5541-52. 2007
  10. pmc The Rpd3/Hda1 family of lysine deacetylases: from bacteria and yeast to mice and men
    Xiang Jiao Yang
    Molecular Oncology Group, Department of Medicine, McGill University Health Center, Montreal, Quebec, H3A 1A1, Canada
    Nat Rev Mol Cell Biol 9:206-18. 2008

Research Grants

  1. Targeted siRNA nanotechnology for intravesical treatment of urologicaldiseases
    Robert M Weiss; Fiscal Year: 2010
  2. Role of IKK in NSCLC: Modulation of SMRT and NF-kappaB
    Marty W Mayo; Fiscal Year: 2012
  3. Rajvir Dahiya; Fiscal Year: 2015
  4. Schahram Akbarian; Fiscal Year: 2014
  5. HUIPING ROSE ZHOU; Fiscal Year: 2015
  6. Bioflavonoid Effects on EGF Signaling and Cell Cycle Pathways in Prostate Cancer
    BARRY MATTHEW MARKAVERICH; Fiscal Year: 2013
  7. Genistein and Prostate Cancer
    Rajvir Dahiya; Fiscal Year: 2010
  8. Improving Epigenetic-based Cell Reprogramming with Proteasome Inhibition
    Jaroslaw Staszkiewicz; Fiscal Year: 2011
  9. Gary B Kaplan; Fiscal Year: 2014
  10. Intermediary Metabolism, Histone Acetylation, and Transcriptional Regulation
    Ales Vancura; Fiscal Year: 2013

Detail Information

Publications393 found, 100 shown here

  1. doi Lysine acetylation targets protein complexes and co-regulates major cellular functions
    Chunaram Choudhary
    Proteomics and Signal Transduction, Max Planck Institute for Biochemistry, Martinsried, Germany
    Science 325:834-40. 2009
    ..Our data demonstrate that the regulatory scope of lysine acetylation is broad and comparable with that of other major posttranslational modifications...
  2. ncbi Anticancer activities of histone deacetylase inhibitors
    Jessica E Bolden
    Cancer Immunology Program, Peter MacCallum Cancer Centre, St Andrews Place, East Melbourne 3002, Victoria, Australia
    Nat Rev Drug Discov 5:769-84. 2006
    b>Histone deacetylases (HDACs) are enzymes involved in the remodelling of chromatin, and have a key role in the epigenetic regulation of gene expression...
  3. ncbi Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase
    S Imai
    Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA
    Nature 403:795-800. 2000
    ..Here we show that yeast and mouse Sir2 proteins are nicotinamide adenine dinucleotide (NAD)-dependent histone deacetylases, which deacetylate lysines 9 and 14 of H3 and specifically lysine 16 of H4...
  4. pmc HDAC2 negatively regulates memory formation and synaptic plasticity
    Ji Song Guan
    Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences
    Nature 459:55-60. 2009
    ..Increased histone-tail acetylation induced by inhibitors of histone deacetylases (HDACis) facilitates learning and memory in wild-type mice as well as in mouse models of neurodegeneration...
  5. ncbi HDAC6 rescues neurodegeneration and provides an essential link between autophagy and the UPS
    Udai Bhan Pandey
    Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Nature 447:859-63. 2007
    ..Morover, these findings suggest that it may be possible to intervene in neurodegeneration by augmenting HDAC6 to enhance autophagy...
  6. pmc Histone deacetylases (HDACs): characterization of the classical HDAC family
    Annemieke J M de Ruijter
    Academic Medical Centre, University of Amsterdam, Amsterdam, The, Netherlands
    Biochem J 370:737-49. 2003
    ..This challenging field has generated many fascinating results which will ultimately lead to a better understanding of the mechanism of gene transcription as a whole...
  7. ncbi The deacetylase HDAC6 regulates aggresome formation and cell viability in response to misfolded protein stress
    Yoshiharu Kawaguchi
    Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA
    Cell 115:727-38. 2003
    ..These findings identify HDAC6 as a crucial player in the cellular management of misfolded protein-induced stress...
  8. ncbi Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer
    Saverio Minucci
    Department of Experimental Oncology, European Institute of Oncology, Via Ripamanti 435, 20141, Milan, Italy
    Nat Rev Cancer 6:38-51. 2006
    b>Histone deacetylases (HDACs) are considered to be among the most promising targets in drug development for cancer therapy, and first-generation histone deacetylase inhibitors (HDACi) are currently being tested in phase I/II clinical ..
  9. ncbi Histone deacetylase inhibitors: molecular mechanisms of action
    W S Xu
    Cell Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Oncogene 26:5541-52. 2007
    ..The plurality of mechanisms of HDACi-induced cell death reflects both the multiple substrates of HDACs and the heterogeneous patterns of molecular alterations present in different cancer cells...
  10. pmc The Rpd3/Hda1 family of lysine deacetylases: from bacteria and yeast to mice and men
    Xiang Jiao Yang
    Molecular Oncology Group, Department of Medicine, McGill University Health Center, Montreal, Quebec, H3A 1A1, Canada
    Nat Rev Mol Cell Biol 9:206-18. 2008
    ..In vertebrates, the Rpd3/Hda1 family contains 11 members, traditionally referred to as histone deacetylases (HDAC) 1-11, which are further grouped into classes I, II and IV...
  11. doi Acetylation of non-histone proteins modulates cellular signalling at multiple levels
    Stephanie Spange
    Leibniz Institute for Age Research Fritz Lipmann Institute, Beutenbergstrasse 11, 07745 Jena, Germany
    Int J Biochem Cell Biol 41:185-98. 2009
    ..The recruitment of histone acetyltransferases and histone deacetylases to the transcriptional machinery is a key element in the dynamic regulation of genes controlling cellular ..
  12. 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
    ..These observations establish SIRT2 as a bona fide tubulin deacetylase...
  13. ncbi Functions of site-specific histone acetylation and deacetylation
    Mona D Shahbazian
    Department of Biological Chemistry, Geffen School of Medicine and the Molecular Biology Institute, University of California, Los Angeles, California 90095, USA
    Annu Rev Biochem 76:75-100. 2007
    ..Determining how these enzymes create distinct acetylation patterns and regulate the functional outcome is an important challenge...
  14. ncbi Determination of the class and isoform selectivity of small-molecule histone deacetylase inhibitors
    Nagma Khan
    TopoTarget UK LTD, 87a Milton Park, Abingdon, Oxon, OX14 4RY, UK
    Biochem J 409:581-9. 2008
    ....
  15. pmc HDAC6 controls autophagosome maturation essential for ubiquitin-selective quality-control autophagy
    Joo Yong Lee
    Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA
    EMBO J 29:969-80. 2010
    ..Our study identifies HDAC6 and the actin cytoskeleton as critical components that define QC autophagy and uncovers a novel regulation of autophagy at the level of autophagosome-lysosome fusion...
  16. doi Histone deacetylase inhibitors in cancer therapy
    Andrew A Lane
    Massachusetts General Hospital Cancer Center, Boston, MA 02214, USA
    J Clin Oncol 27:5459-68. 2009
    ..This compaction blocks gene transcription and inhibits differentiation, providing a rationale for developing HDAC inhibitors...
  17. ncbi HATs and HDACs: from structure, function and regulation to novel strategies for therapy and prevention
    X J Yang
    Molecular Oncology Group, Department of Medicine, McGill University Health Center, Montreal, Quebec, Canada
    Oncogene 26:5310-8. 2007
    ....
  18. ncbi Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription
    P L Jones
    Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, National Institute of Health, Bethesda, Maryland 20892 5431, USA
    Nat Genet 19:187-91. 1998
    ..These results establish a direct causal relationship between DNA methylation-dependent transcriptional silencing and the modification of chromatin...
  19. ncbi Inhibition of histone deacetylase activity by butyrate
    James R Davie
    Manitoba Institute of Cell Biology, Winnipeg, Manitoba, Canada
    J Nutr 133:2485S-2493S. 2003
    ..Pending the cell background, the nonproliferating cells may enter differentiation or apoptotic pathways. The potential of butyrate and HDAC inhibitors in the prevention and treatment of cancer is presented...
  20. ncbi Recovery of learning and memory is associated with chromatin remodelling
    Andre Fischer
    Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge 02139, USA
    Nature 447:178-82. 2007
    ..Moreover, increased histone acetylation by inhibitors of histone deacetylases induced sprouting of dendrites, an increased number of synapses, and reinstated learning behaviour and ..
  21. pmc Parkin-mediated K63-linked polyubiquitination targets misfolded DJ-1 to aggresomes via binding to HDAC6
    James A Olzmann
    Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322, USA
    J Cell Biol 178:1025-38. 2007
    ....
  22. ncbi Dimethyl sulfoxide to vorinostat: development of this histone deacetylase inhibitor as an anticancer drug
    Paul A Marks
    Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, USA
    Nat Biotechnol 25:84-90. 2007
    ..A new drug application was approved by the US Food and Drug Administration for vorinostat for treatment of cutaneous T-cell lymphoma. More potent analogs of SAHA have shown unacceptable toxicity...
  23. ncbi Histone deacetylase inhibitors: overview and perspectives
    Milos Dokmanovic
    Cell Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Mol Cancer Res 5:981-9. 2007
    ..A hypothesis is presented to explain the relative resistance of normal cells to HDACi-induced cell death...
  24. pmc HDAC3 is a critical negative regulator of long-term memory formation
    Susan C McQuown
    Department of Neurobiology and Behavior, Center for the Neurobiology of Learning and Memory, University of California, Irvine, Irvine, California 92697, USA
    J Neurosci 31:764-74. 2011
    ..The interplay between histone acetyltranserases and histone deacetylases (HDACs) is pivotal for the regulation of gene expression required for long-term memory processes...
  25. 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...
  26. ncbi Histone deacetylase inhibitors arrest polyglutamine-dependent neurodegeneration in Drosophila
    J S Steffan
    Department of Psychiatry and Human Behavior, Gillespie 2121, University of California, Irvine, California 92697, USA
    Nature 413:739-43. 2001
    ..These findings raise the possibility that therapy with HDAC inhibitors may slow or prevent the progressive neurodegeneration seen in Huntington's disease and other polyglutamine-repeat diseases, even after the onset of symptoms...
  27. pmc Histone deacetylases mediate the silencing of miR-15a, miR-16, and miR-29b in chronic lymphocytic leukemia
    Deepa Sampath
    Departments of Experimental Therapeutics, The University of Texas M D Anderson Cancer Center, 1901 East Road, Houston, TX 77054, USA
    Blood 119:1162-72. 2012
    ..In the present study, we show that the histone deacetylases (HDACs) are overexpressed in CLL and mediate the epigenetic silencing of miR-15a, miR-16, and miR-29b...
  28. pmc Structure of HDAC3 bound to co-repressor and inositol tetraphosphate
    Peter J Watson
    Henry Wellcome Laboratories of Structural Biology, Department of Biochemistry, University of Leicester, Leicester LE1 9HN, UK
    Nature 481:335-40. 2012
    ..This mechanism for the activation of HDAC3 appears to be conserved in class I HDACs from yeast to humans, and opens the way to novel therapeutic opportunities...
  29. pmc CBP/p300-mediated acetylation of histone H3 on lysine 56
    Chandrima Das
    Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, PO Box 6511, Aurora Colorado 80045, USA
    Nature 459:113-7. 2009
    ....
  30. pmc Identification and characterization of a family of mammalian methyl-CpG binding proteins
    B Hendrich
    Institute of Cell and Molecular Biology, University of Edinburgh, Edinburgh EH9 3JR, Scotland
    Mol Cell Biol 18:6538-47. 1998
    ..The data demonstrate that MBD2 and MBD4 bind specifically to methyl-CpG in vitro and in vivo and are therefore likely to be mediators of the biological consequences of the methylation signal...
  31. ncbi HDAC6 and microtubules are required for autophagic degradation of aggregated huntingtin
    Atsushi Iwata
    Department of Biological Sciences, Bio X Program, Stanford University, Stanford, California 94305 5430, USA
    J Biol Chem 280:40282-92. 2005
    ..These data suggest that HDAC6-dependent retrograde transport on microtubules is used by cells to increase the efficiency and selectivity of autophagic degradation...
  32. ncbi MEF2: a central regulator of diverse developmental programs
    Matthew J Potthoff
    Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390 9148, USA
    Development 134:4131-40. 2007
    ..Recent studies have revealed MEF2 to form an intimate partnership with class IIa histone deacetylases, which together function as a point of convergence of multiple epigenetic regulatory mechanisms...
  33. doi HDAC6 inhibitors reverse axonal loss in a mouse model of mutant HSPB1-induced Charcot-Marie-Tooth disease
    Constantin d'Ydewalle
    Vesalius Research Center, VIB and K U Leuven, Campus Gasthuisberg, Leuven, Belgium
    Nat Med 17:968-74. 2011
    ..Our findings demonstrate the pathogenic role of α-tubulin deacetylation in mutant HSPB1-induced neuropathies and offer perspectives for using HDAC6 inhibitors as a therapeutic strategy for hereditary axonopathies...
  34. ncbi HDAC6 regulates Hsp90 acetylation and chaperone-dependent activation of glucocorticoid receptor
    Jeffrey J Kovacs
    Department of Pharmacology and Cancer Biology, Duke University, Durham, North Carolina 27710, USA
    Mol Cell 18:601-7. 2005
    ..Our results identify Hsp90 as a target of HDAC6 and suggest reversible acetylation as a unique mechanism that regulates Hsp90 chaperone complex activity...
  35. doi A redox-dependent pathway for regulating class II HDACs and cardiac hypertrophy
    Tetsuro Ago
    Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ 07103, USA
    Cell 133:978-93. 2008
    ..upregulates DnaJb5, a heat shock protein 40, and forms a multiple-protein complex with DnaJb5 and class II histone deacetylases (HDACs), master negative regulators of cardiac hypertrophy...
  36. ncbi hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase
    H Vaziri
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Cell 107:149-59. 2001
    ..In contrast, expression of a catalytically inactive hSir2 protein potentiates p53-dependent apoptosis and radiosensitivity. We propose that hSir2 is involved in the regulation of p53 function via deacetylation...
  37. pmc In vivo destabilization of dynamic microtubules by HDAC6-mediated deacetylation
    Akihisa Matsuyama
    Chemical Genetics Laboratory, Wako, Saitama 351 0198, Japan
    EMBO J 21:6820-31. 2002
    Trichostatin A (TSA) inhibits all histone deacetylases (HDACs) of both class I and II, whereas trapoxin (TPX) cannot inhibit HDAC6, a cytoplasmic member of class II HDACs...
  38. ncbi Asymmetric inheritance of oxidatively damaged proteins during cytokinesis
    Hugo Aguilaniu
    Department of Cell and Molecular Biology Microbiology, Goteborg University, Goteborg, Sweden
    Science 299:1751-3. 2003
    ..These findings suggest that a genetically determined, Sir2p-dependent asymmetric inheritance of oxidatively damaged proteins may contribute to free-radical defense and the fitness of newborn cells...
  39. ncbi Molecular evolution of the histone deacetylase family: functional implications of phylogenetic analysis
    Ivan V Gregoretti
    Walther Cancer Center and Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46628, USA
    J Mol Biol 338:17-31. 2004
    b>Histone deacetylases (HDACs) modify core histones and participate in large regulatory complexes that both suppress and enhance transcription. Recent studies indicate that some HDACs can act on non-histone proteins as well...
  40. ncbi Stat3 dimerization regulated by reversible acetylation of a single lysine residue
    Zheng Long Yuan
    Department of Surgery, Brown University Medical School Rhode Island Hospital, Providence, RI 02903, USA
    Science 307:269-73. 2005
    ....
  41. ncbi Acetylation and deacetylation of non-histone proteins
    Michele A Glozak
    H Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, SRB 23011, Tampa, FL 33612, USA
    Gene 363:15-23. 2005
    ..Deacetylation of these non-histone proteins by histone deacetylases (HDACs) opens yet another exciting new field of discovery in the role of the dynamic acetylation and ..
  42. ncbi Histone deacetylases and cancer
    M A Glozak
    H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
    Oncogene 26:5420-32. 2007
    b>Histone deacetylases (HDACs) regulate the expression and activity of numerous proteins involved in both cancer initiation and cancer progression...
  43. pmc Class IIa histone deacetylases are hormone-activated regulators of FOXO and mammalian glucose homeostasis
    Maria M Mihaylova
    Molecular and Cell Biology Laboratory, The Salk Institute for Biological Studies, 10010 N Torrey Pines Road, La Jolla, CA 92037, USA
    Cell 145:607-21. 2011
    Class IIa histone deacetylases (HDACs) are signal-dependent modulators of transcription with established roles in muscle differentiation and neuronal survival...
  44. ncbi Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan
    Konrad T Howitz
    BIOMOL Research Laboratories, Inc, 5120 Butler Pike, Plymouth Meeting, Pennsylvania 19462, USA
    Nature 425:191-6. 2003
    ..We discuss possible evolutionary origins of this phenomenon and suggest new lines of research into the therapeutic use of sirtuin activators...
  45. pmc Signal-dependent nuclear export of a histone deacetylase regulates muscle differentiation
    T A McKinsey
    Department of Molecular Biology, The University of Texas Southwestern Medical Center at Dallas, 75390 9148, USA
    Nature 408:106-11. 2000
    ..MEF2 proteins also interact with the class II histone deacetylases HDAC4 and HDAC5, resulting in repression of MEF2-dependent genes...
  46. pmc Histone deacetylase inhibition-mediated neuronal differentiation of multipotent adult neural progenitor cells
    Jenny Hsieh
    Laboratory of Genetics, The Salk Institute, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 101:16659-64. 2004
    ..These results suggest that VPA promotes neuronal fate and inhibits glial fate simultaneously through the induction of neurogenic transcription factors including NeuroD...
  47. ncbi Histone deacetylase 3 (HDAC3) and other class I HDACs regulate colon cell maturation and p21 expression and are deregulated in human colon cancer
    Andrew J Wilson
    Department of Oncology, Albert Einstein Cancer Center, Montefiore Medical Center, Bronx, New York 10467, USA
    J Biol Chem 281:13548-58. 2006
    Inhibitors of histone deacetylases (HDACs) induce growth arrest, differentiation, and apoptosis of colon cancer cell lines in vitro and have demonstrated anti-cancer efficacy in clinical trials...
  48. ncbi Duration of nuclear NF-kappaB action regulated by reversible acetylation
    - Chen Lf
    Gladstone Institute of Virology and Immunology, Department of Medicine, University of California, San Francisco, CA 94141, USA
    Science 293:1653-7. 2001
    ....
  49. ncbi Substrate-specific activation of sirtuins by resveratrol
    Matt Kaeberlein
    Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA
    J Biol Chem 280:17038-45. 2005
    ..In light of these findings, the mechanism accounting for putative longevity effects of resveratrol should be reexamined...
  50. ncbi Negative control of p53 by Sir2alpha promotes cell survival under stress
    J Luo
    Institute of Cancer Genetics and Department of Pathology, College of Physicians and Surgeons, Columbia University, 1150 St Nicholas Avenue, New York, NY 10032, USA
    Cell 107:137-48. 2001
    ..These results have significant implications regarding an important role for Sir2alpha in modulating the sensitivity of cells in p53-dependent apoptotic response and the possible effect in cancer therapy...
  51. ncbi Structures of a histone deacetylase homologue bound to the TSA and SAHA inhibitors
    M S Finnin
    Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Nature 401:188-93. 1999
    b>Histone deacetylases (HDACs) mediate changes in nucleosome conformation and are important in the regulation of gene expression...
  52. ncbi The Sir2 family of protein deacetylases
    Gil Blander
    Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Annu Rev Biochem 73:417-35. 2004
    ..We summarize the current knowledge of the Sir2 homologs from different organisms, and finally we discuss the role of Sir2 in caloric restriction and aging...
  53. pmc Histone deacetylase inhibitors enhance memory and synaptic plasticity via CREB:CBP-dependent transcriptional activation
    Christopher G Vecsey
    Neuroscience Graduate Group, University of Pennsylvania, 19104, USA
    J Neurosci 27:6128-40. 2007
    ..Our results suggest that HDAC inhibitors enhance memory processes by the activation of key genes regulated by the CREB:CBP transcriptional complex...
  54. doi Clinical studies of histone deacetylase inhibitors
    H Miles Prince
    Division of Haematology and Medical Oncology, Peter MacCallum Cancer Centre, East Melbourne, Melbourne, Australia and University of Melbourne, Parkville, Victoria, Australia
    Clin Cancer Res 15:3958-69. 2009
    ..The use of the biomarker of histone hyperacetylation has been useful as a guide to target specificity, but generally does not predict for response and the search for more clinically relevant biomarkers must continue...
  55. pmc Histone deacetylase: a potential therapeutic target for fibrotic disorders
    Maoyin Pang
    Department of Medicine, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Middle House 301, 593 Eddy Street, Providence, RI 02903, USA
    J Pharmacol Exp Ther 335:266-72. 2010
    b>Histone deacetylases (HDACs) are enzymes that balance the acetylation activities of histone acetyltransferases on chromatin remodeling and play essential roles in regulating gene transcription...
  56. ncbi Role of histone H3 lysine 9 methylation in epigenetic control of heterochromatin assembly
    J Nakayama
    Cold Spring Harbor Laboratory, Post Office Box 100, Cold Spring Harbor, NY 11724, USA
    Science 292:110-3. 2001
    ..These data define a conserved pathway wherein sequential histone modifications establish a "histone code" essential for the epigenetic inheritance of heterochromatin assembly...
  57. 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
    ..This pathway, distinct from existing ageing models for yeast, may represent an evolutionarily conserved function of sirtuins in regulation of replicative ageing by maintenance of intact telomeric chromatin...
  58. pmc Domain-selective small-molecule inhibitor of histone deacetylase 6 (HDAC6)-mediated tubulin deacetylation
    Stephen J Haggarty
    Department of Molecular and Cellular Biology, and Harvard Institute of Chemistry and Cell Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA
    Proc Natl Acad Sci U S A 100:4389-94. 2003
    ..They also suggest that small molecules that selectively inhibit HDAC6-mediated alpha-tubulin deacetylation, a first example of which is tubacin, might have therapeutic applications as antimetastatic and antiangiogenic agents...
  59. doi HDAC6: a key regulator of cytoskeleton, cell migration and cell-cell interactions
    Agustin Valenzuela-Fernandez
    Departamento de Medicina Física y Farmacología, Facultad de Medicina and Instituto de Tecnologías Biomédicas ITB, Universidad de La Laguna, Tenerife, Spain
    Trends Cell Biol 18:291-7. 2008
    ....
  60. doi A DNAJB chaperone subfamily with HDAC-dependent activities suppresses toxic protein aggregation
    Jurre Hageman
    Department of Cell Biology, Section of Radiation and Stress Cell Biology, University Medical Center Groningen and University of Groningen, 9700 RB Groningen, The Netherlands
    Mol Cell 37:355-69. 2010
    ..is involved in substrate binding, formation of polydisperse oligomeric complexes, and interaction with histone deacetylases (HDAC4, HDAC6, SIRT2). Inhibiting HDAC4 reduced DNAJB8 function...
  61. ncbi Upregulation and nuclear recruitment of HDAC1 in hormone refractory prostate cancer
    Kalipso Halkidou
    School of Surgical and Reproductive Sciences, The Medical School, University of Newcastle upon Tyne, United Kingdom
    Prostate 59:177-89. 2004
    ..Histone deacetylase 1 (HDAC1) is a co-repressor involved in differentiation and proliferation control. It is upregulated in malignant compared to benign tissue, and targets a number of transcription factors including p53...
  62. ncbi Chromatin remodeling is a key mechanism underlying cocaine-induced plasticity in striatum
    Arvind Kumar
    Department of Psychiatry and Center for Basic Neuroscience, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA
    Neuron 48:303-14. 2005
    ..Furthermore, modulating histone deacetylase activity alters locomotor and rewarding responses to cocaine. Thus, chromatin remodeling is an important regulatory mechanism underlying cocaine-induced neural and behavioral plasticity...
  63. doi Therapeutic application of histone deacetylase inhibitors for central nervous system disorders
    Aleksey G Kazantsev
    Harvard Medical School, Massachusetts General Hospital, Mass General Institute for Neurodegenerative Disease, Charlestown, Massachusetts 02129 4404, USA
    Nat Rev Drug Discov 7:854-68. 2008
    b>Histone deacetylases (HDACs)--enzymes that affect the acetylation status of histones and other important cellular proteins--have been recognized as potentially useful therapeutic targets for a broad range of human disorders...
  64. 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
    ..We propose that binding of resveratrol to SIRT1 promotes a conformational change that better accommodates the attached coumarin group...
  65. pmc Multiple roles of HDAC inhibition in neurodegenerative conditions
    De Maw Chuang
    Molecular Neurobiology Section, National Institute of Mental Health, National Institutes of Health, 10 Center Drive MSC 1363, Bethesda, MD 20892 1363, USA
    Trends Neurosci 32:591-601. 2009
    b>Histone deacetylases (HDACs) play a key role in homeostasis of protein acetylation in histones and other proteins and in regulating fundamental cellular activities such as transcription...
  66. pmc The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms
    M Kaeberlein
    Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Genes Dev 13:2570-80. 1999
    ..Sir2p is a limiting component in promoting yeast longevity, and increasing the gene dosage extends the life span in wild-type cells. A possible role of the conserved SIR2 in mammalian aging is discussed...
  67. pmc A core SMRT corepressor complex containing HDAC3 and TBL1, a WD40-repeat protein linked to deafness
    M G Guenther
    Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine and Genetics, and The Penn Diabetes Center, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 USA
    Genes Dev 14:1048-57. 2000
    ..Intriguingly, loss-of-function TRbeta mutations cause deafness in mice and humans. These results define a new TR corepressor complex with a physical link to histone structure and a potential biological link to deafness...
  68. pmc Both corepressor proteins SMRT and N-CoR exist in large protein complexes containing HDAC3
    J Li
    Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
    EMBO J 19:4342-50. 2000
    ..These findings thus establish both SMRT and N-CoR complexes as bona fide HDAC-containing complexes and shed new light on the molecular pathways by which N-CoR and SMRT function in transcriptional repression...
  69. pmc Histone deacetylase inhibitor selectively induces p21WAF1 expression and gene-associated histone acetylation
    V M Richon
    DeWitt Wallace Research Laboratory, Cell Biology Program, Memorial Sloan Kettering Cancer Center and Graduate School of Medical Sciences of Cornell Medical School, New York, NY 10021, USA
    Proc Natl Acad Sci U S A 97:10014-9. 2000
    b>Histone deacetylases (HDACs) catalyze the removal of acetyl groups on the amino-terminal lysine residues of core nucleosomal histones. This activity is associated generally with transcriptional repression...
  70. ncbi Histone H3 methylation by Set2 directs deacetylation of coding regions by Rpd3S to suppress spurious intragenic transcription
    Michael J Carrozza
    Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA
    Cell 123:581-92. 2005
    ..This erases transcription elongation-associated acetylation to suppress intragenic transcription initiation...
  71. pmc HDAC-6 interacts with and deacetylates tubulin and microtubules in vivo
    Yu Zhang
    Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland
    EMBO J 22:1168-79. 2003
    ....
  72. ncbi HDAC6 is a microtubule-associated deacetylase
    Charlotte Hubbert
    Department of Pharmacology and Cancer Biology, Duke University, Durham, North Carolina 27710, USA
    Nature 417:455-8. 2002
    ..Our results show that HDAC6 is the tubulin deacetylase, and provide evidence that reversible acetylation regulates important biological processes beyond histone metabolism and gene transcription...
  73. pmc Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase
    Fan Yeung
    Department of Biochemistry and Molecular Genetics, The University of Virginia, Charlottesville, VA 22908, USA
    EMBO J 23:2369-80. 2004
    ....
  74. pmc Suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, ameliorates motor deficits in a mouse model of Huntington's disease
    Emma Hockly
    Medical and Molecular Genetics, Guy s, King s and St Thomas School of Medicine, King s College London, Eighth Floor Guy s Tower, Guy s Hospital, London SE1 9RT, United Kingdom
    Proc Natl Acad Sci U S A 100:2041-6. 2003
    ..SAHA dramatically improved the motor impairment in R6/2 mice, clearly validating the pursuit of this class of compounds as HD therapeutics...
  75. ncbi Histone deacetylase 6 inhibition compensates for the transport deficit in Huntington's disease by increasing tubulin acetylation
    Jim P Dompierre
    Institut Curie and Centre National de la Recherche Scientifique Unité Mixte de Recherche 146, Orsay, France
    J Neurosci 27:3571-83. 2007
    ..Our findings reveal that HDAC6 inhibition and acetylation at lysine 40 of alpha-tubulin may be therapeutic targets of interest in disorders such as HD in which intracellular transport is altered...
  76. pmc Human SIR2 deacetylates p53 and antagonizes PML/p53-induced cellular senescence
    Emma Langley
    Wellcome Institute Cancer Research UK and Department of Pathology, University of Cambridge, Tennis Court Road, CB2 1QR, UK
    EMBO J 21:2383-96. 2002
    ..Taken together, our data establish the SIRT1 deacetylase as a novel negative regulator of p53 function capable of modulating cellular senescence...
  77. doi Histone deacetylase inhibitors: current status and overview of recent clinical trials
    Xujun Ma
    Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota 55905, USA
    Drugs 69:1911-34. 2009
    ..The combination of HDAC inhibitors with other anticancer agents including epigenetic or chemotherapeutic agents demonstrated favourable clinical outcome...
  78. ncbi Post-activation turn-off of NF-kappa B-dependent transcription is regulated by acetylation of p65
    Rosemary Kiernan
    Laboratoire de Virologie Moleculaire, Institut de Genetique Humaine, Montpellier 34296, France
    J Biol Chem 278:2758-66. 2003
    ..We propose that acetylation of p65 plays a key role in IkappaBetaalpha-mediated attenuation of NF-kappaBeta transcriptional activity which is an important process that restores the latent state in post-induced cells...
  79. pmc Phase I study of an oral histone deacetylase inhibitor, suberoylanilide hydroxamic acid, in patients with advanced cancer
    William Kevin Kelly
    Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center and Joan and Sanford Weill Medical College of Cornell University, New York, NY 10021, USA
    J Clin Oncol 23:3923-31. 2005
    ..To determine the safety, dosing schedules, pharmacokinetic profile, and biologic effect of orally administered histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) in patients with advanced cancer...
  80. ncbi The Connectivity Map: using gene-expression signatures to connect small molecules, genes, and disease
    Justin Lamb
    Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA
    Science 313:1929-35. 2006
    ..These results indicate the feasibility of the approach and suggest the value of a large-scale community Connectivity Map project...
  81. pmc Class II histone deacetylases act as signal-responsive repressors of cardiac hypertrophy
    Chun Li Zhang
    Department of Molecular Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas 75390, USA
    Cell 110:479-88. 2002
    ..We show here that class II histone deacetylases (HDACs), which repress MEF2 activity, are substrates for a stress-responsive kinase specific for conserved ..
  82. pmc Butyrate improves insulin sensitivity and increases energy expenditure in mice
    Zhanguo Gao
    Antioxidant and Gene Regulation Laboratory, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA, USA
    Diabetes 58:1509-17. 2009
    ..We examined the role of butyric acid, a short-chain fatty acid formed by fermentation in the large intestine, in the regulation of insulin sensitivity in mice fed a high-fat diet...
  83. ncbi HDAC6 a new cellular stress surveillance factor
    Patrick Matthias
    Friedrich Miescher Institute for Biomedical Research, Novartis Research Foundation, Basel, Switzerland
    Cell Cycle 7:7-10. 2008
    ..HDAC6 appears both as a sensor of stressful stimuli and as an effector, which, thanks to its wide range of activities, mediates and coordinates appropriate cell responses...
  84. doi Histone deacetylases 1 and 2 are expressed at distinct stages of neuro-glial development
    Jessica L MacDonald
    Department of Zoology, University of British Columbia, Vancouver, Canada
    Dev Dyn 237:2256-67. 2008
    The deacetylation of histone proteins, catalyzed by histone deacetylases (HDACs), is a common epigenetic modification of chromatin, associated with gene silencing...
  85. pmc SIRT3 is a stress-responsive deacetylase in cardiomyocytes that protects cells from stress-mediated cell death by deacetylation of Ku70
    Nagalingam R Sundaresan
    University of Chicago Medical Center, Committee on Cellular and Molecular Physiology, Biological Science Division, University of Chicago, Chicago, Illinois 60637, USA
    Mol Cell Biol 28:6384-401. 2008
    ..These studies underscore an essential role of SIRT3 in the survival of cardiomyocytes in stress situations...
  86. doi Biomarkers for predicting clinical responses to HDAC inhibitors
    Lindsay Stimson
    Dept of Clinical Pharmacology, Laboratory of Cancer Biology, Oxford, United Kingdom
    Cancer Lett 280:177-83. 2009
    ..manipulation of acetylation has been possible with the identification of small molecule inhibitors of histone deacetylases (HDAC), the enzymes responsible for deacetylating lysine residues...
  87. pmc Genetic knock-down of HDAC7 does not ameliorate disease pathogenesis in the R6/2 mouse model of Huntington's disease
    Caroline L Benn
    Department of Medical and Molecular Genetics, King s College London School of Medicine, King s College London, London, UK
    PLoS ONE 4:e5747. 2009
    ..Therefore, we conclude that the beneficial effects of HDAC inhibitors are not predominantly mediated through the inhibition of HDAC7...
  88. ncbi Sirtuins in aging and age-related disease
    Valter D Longo
    Department of Molecular and Computational Biology, Andrus Gerontology Center, University of Southern California, Los Angeles, CA 90089, USA
    Cell 126:257-68. 2006
    ..Here we examine the roles of Sirtuins in diverse eukaryotic species, with special emphasis on their links to aging and age-related diseases including cancer, diabetes, and neurodegenerative disorders...
  89. 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
    ..Discovery of an intrinsic deacetylation activity for the conserved SIR2 family provides a mechanism for modifying histones and other proteins to regulate transcription and diverse biological processes...
  90. ncbi Expression and function of HD2-type histone deacetylases in Arabidopsis development
    Changhe Zhou
    Department of Biology, West Virginia University, Morgantown, WV 26506, USA
    Plant J 38:715-24. 2004
    HD2 (histone deacetylase) proteins are plant-specific histone deacetylases (HDACs). The Arabidopsis genome contains four HD2 genes, namely HD2A, HD2B, HD2C, and HD2D...
  91. pmc Histone deacetylase 3 (HDAC3) activity is regulated by interaction with protein serine/threonine phosphatase 4
    Xiaohong Zhang
    H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612, USA
    Genes Dev 19:827-39. 2005
    ....
  92. pmc Histone deacetylases and cancer
    Bruna Barneda-Zahonero
    Cellular Differentiation Group, Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute, Av Gran Via s n km 2 7, 08908 L Hospitalet, Barcelona, Spain
    Mol Oncol 6:579-89. 2012
    ..are achieved by the antagonistic actions of two families of enzymes, histone acetyltransferases (HATs) and histone deacetylases (HDACs)...
  93. pmc Protein kinases C and D mediate agonist-dependent cardiac hypertrophy through nuclear export of histone deacetylase 5
    Rick B Vega
    Department of Molecular Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390 9148, USA
    Mol Cell Biol 24:8374-85. 2004
    ..Recently, we showed that class II histone deacetylases (HDACs) suppress cardiac hypertrophy and that stress signals neutralize this repressive function by ..
  94. pmc CaM kinase II selectively signals to histone deacetylase 4 during cardiomyocyte hypertrophy
    Johannes Backs
    Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9148, USA
    J Clin Invest 116:1853-64. 2006
    Class IIa histone deacetylases (HDACs) regulate a variety of cellular processes, including cardiac growth, bone development, and specification of skeletal muscle fiber type...
  95. pmc Essential function of histone deacetylase 1 in proliferation control and CDK inhibitor repression
    Gerda Lagger
    Institute of Medical Biochemistry, Division of Molecular Biology, University of Vienna, Vienna Biocenter, Dr Bohr Gasse 9 2, A 1030 Vienna, Austria
    EMBO J 21:2672-81. 2002
    b>Histone deacetylases (HDACs) modulate chromatin structure and transcription, but little is known about their function in mammalian development...
  96. pmc HDAC6-p97/VCP controlled polyubiquitin chain turnover
    Cyril Boyault
    INSERM U309, Laboratoire de Biologie Moléculaire et Cellulaire de la Différenciation, Equipe chromatine et expression des gènes, Institut Albert Bonniot, Faculte de Medecine, Domaine de la Merci, La Tronche, France
    EMBO J 25:3357-66. 2006
    ....
  97. ncbi Histone-deacetylase inhibitors: novel drugs for the treatment of cancer
    Ricky W Johnstone
    Cancer Immunology Program, Peter MacCallum Cancer Institute, Trescowthick Research Laboratories, Smorgon Family Building, St Andrews Place, East Melbourne, 3002 Victoria, Australia
    Nat Rev Drug Discov 1:287-99. 2002
    The opposing actions of histone acetyltransferases (HATs) and histone deacetylases (HDACs) allow gene expression to be exquisitely regulated through chromatin remodelling...
  98. pmc HDAC4 and PCAF bind to cardiac sarcomeres and play a role in regulating myofilament contractile activity
    Mahesh P Gupta
    Department of Surgery, Committee on Molecular Medicine, Biological Science Division, University of Chicago, 5841 S Maryland Avenue, Chicago, IL 60637, USA
    J Biol Chem 283:10135-46. 2008
    ..These studies provide the first evidence that HATs and HDACs play a role in regulation of muscle contraction...
  99. ncbi Histone deacetylase is a direct target of valproic acid, a potent anticonvulsant, mood stabilizer, and teratogen
    C J Phiel
    Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6148, USA
    J Biol Chem 276:36734-41. 2001
    ..Based on these observations, we propose that inhibition of histone deacetylase provides a mechanism for valproic acid-induced birth defects and could also explain the efficacy of valproic acid in the treatment of bipolar disorder...
  100. ncbi Estrogen receptor-alpha directs ordered, cyclical, and combinatorial recruitment of cofactors on a natural target promoter
    Raphaël Métivier
    European Molecular Biology Laboratory, Meyerhofstrasse 1, D 69117 Heidelberg, Germany
    Cell 115:751-63. 2003
    ..Furthermore, the unanticipated findings of key roles for histone deacetylases and nucleosome-remodeling complexes in limiting transcription implies that transcriptional activation is a ..
  101. ncbi The NuRD component Mbd3 is required for pluripotency of embryonic stem cells
    Keisuke Kaji
    Centre Development in Stem Cell Biology, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, Edinburgh, EH9 3JQ, Scotland, UK
    Nat Cell Biol 8:285-92. 2006
    ..Our findings define a role for epigenetic silencing in the cell-fate commitment of pluripotent cells...

Research Grants74

  1. Targeted siRNA nanotechnology for intravesical treatment of urologicaldiseases
    Robert M Weiss; Fiscal Year: 2010
    ..Our first test of these nanoparticles will use a mouse model of bladder cancer. Thus, we can determine the therapeutic potential of siRNA for treatment of urologic diseases. ..
  2. Role of IKK in NSCLC: Modulation of SMRT and NF-kappaB
    Marty W Mayo; Fiscal Year: 2012
    ..The overall goal of this project is use these newly identified gene products as novel therapeutic targets for detection and treatment of NSCLC. ..
  3. Rajvir Dahiya; Fiscal Year: 2015
    ..The expression and activities of histone acetyltransferases (HATs) and histone deacetylases (HDACs) in miRNA transfected kidney cancer cells will be analyzed...
  4. Schahram Akbarian; Fiscal Year: 2014
    ..and electroconvulsive seizures, induce dynamic changes in histone acetylation, and (ii) drugs that inhibit histone deacetylases (HDACs) exhibit antidepressant-like effects, or enhance the therapeutic effect of a conventional ..
  5. HUIPING ROSE ZHOU; Fiscal Year: 2015
    ..of SphK2 by ERK1/2 increases nuclear S1P levels, which has been shown to be an inhibitor of specific histone deacetylases (HDAC 1 and 2)...
  6. Bioflavonoid Effects on EGF Signaling and Cell Cycle Pathways in Prostate Cancer
    BARRY MATTHEW MARKAVERICH; Fiscal Year: 2013
    ..Specific coregulators (histone acetyl transferases;HAT's and histone deacetylases;HDAC's) recruited to EGFR, c-Fos, PLK1 and CDKN1B promoters will be identified (via re-ChIP assays) ..
  7. Genistein and Prostate Cancer
    Rajvir Dahiya; Fiscal Year: 2010
    ....
  8. Improving Epigenetic-based Cell Reprogramming with Proteasome Inhibition
    Jaroslaw Staszkiewicz; Fiscal Year: 2011
    ..DNA * methyltransferases and histone deacetylases) using interfering RNA technology;3) modulating epigenetic * regulatory components with small molecules;and ..
  9. Gary B Kaplan; Fiscal Year: 2014
    ..This proposal examines new treatment approaches using pharmacological and behavioral treatments to extinguish cue reactivity in an animal model. Such approaches can inform future clinical trials for opiate abusing veterans. ..
  10. Intermediary Metabolism, Histone Acetylation, and Transcriptional Regulation
    Ales Vancura; Fiscal Year: 2013
    ..Perturbation of the balanced action of histone acetyltransferases (HATs) and histone deacetylases (HDACs) alters the expression pattern of genes involved in cellular growth, resulting in tumorigenesis...
  11. Epigenetic downregulation of the antibody response and inhibition of autoimmunity
    Paolo Casali; Fiscal Year: 2013
    ....
  12. SUSAN F KEAY; Fiscal Year: 2016
    ..BPS/IC cells indeed display an abnormal complement of certain gene regulatory proteins (including specific histone deacetylases (HDACs), transcription factors, and microRNAs) that could explain their abnormal gene expression and ..
  13. Regulation of Bile Acid Synthesis by Nuclear Receptors
    John Y L Chiang; Fiscal Year: 2010
    ..This study could contribute to understanding the mechanisms of metabolic diseases caused by dysregulation of bile acid synthesis and develop therapeutic agents to treat dyslipidemia, liver diseases, obesity and type II diabetes. ..
  14. Biomarkers to Assess Selenium Chemoprevention for NSCLC
    Steven A Belinsky; Fiscal Year: 2012
    ..Studies will also assess whether these same biomarkers can predict cancer recurrence. Finally, a cocktail of agents with minimal side effects is being evaluated that could ultimately be used in the prevention of lung cancer in humans. ..
  15. Juanita L Merchant; Fiscal Year: 2014
    ..Collectively, these studies will establish a link between ZBP-89 and pATMS1981, in the biosynthesis and function of 5HT in response to luminal butyrate. ..
  16. Leena A Hilakivi-Clarke; Fiscal Year: 2015
    ....
  17. Beta-cell Proliferation
    Fredric E Wondisford; Fiscal Year: 2013
    ..These studies of in vivo mechanisms of [unreadable]-cell proliferation may provide therapeutic approaches for diabetes mellitus in humans. ..
  18. Rajvir Dahiya; Fiscal Year: 2014
    ..We will also investigate whether histone acetylation, chromatin remodeling and associated enzymes (histone deacetylases and histone acetyltransferases) play a role in controlling expression of specific miRNAs...
  19. Scott W Hiebert; Fiscal Year: 2014
    DESCRIPTION (provided by applicant): Histone deacetylases regulate chromatin structure, transcription, replication, and DNA repair/recombination...
  20. Gene Transcription in SLE
    George C Tsokos; Fiscal Year: 2012
    ..The proposed studies will explore the mechanisms that lead to decreased production of interleukin-2 in order to identify molecules that we can target for therapeutic purposes. ..
  21. Activity Dependent Signaling in Adult Skeletal Muscle Fiber Plasticity
    Martin F Schneider; Fiscal Year: 2012
    ..2) To determine the molecular mechanisms for the differential regulation of two class II histone deacetylases, HDACs 4 and 5, which bind to and repress the activity of intra nuclear MEF2, a transcription factor which ..
  22. Nicola C Partridge; Fiscal Year: 2016
    ..Moreover, it will define how HDACs contribute to this. In so doing, the data will also provide new perspectives into treatment of disorders of calcium metabolism, cancer-associated bone disease and other bone disorders. ..
  23. The Role of the Nuclear Lamina in Chromatin Organization and Gene Expression in N
    Marcos Estecio; Fiscal Year: 2012
    ....
  24. Prevention of acute GvHD by inhibition of cdk2
    Vassiliki A Boussiotis; Fiscal Year: 2012
    ..on specific sites thereby reversing its ability to sequester E2F, and allowing for interaction of Rb with histone deacetylases (HDAC) and other chromatin remodeling proteins...
  25. Molecular Genetics of Caloric Restriction in Aging Flies
    Blanka Rogina; Fiscal Year: 2013
    ..It will reveal how reduced caloric intake affects metabolism and life span, and provide the foundation for the development of new therapies for the treatments of age-associated diseases in humans. ..
  26. Evolutionary Analysis of the Histone Deacetylase Family: Biomedical Research
    JOSEPH LEWIS GRAVES; Fiscal Year: 2011
    ..PUBLIC HEALTH RELEVANCE: The histone deacetylases are proteins that play an important role in gene expression...
  27. Study on the intracellular Network of TBX3
    Taosheng Huang; Fiscal Year: 2010
    ..Elucidation of the TBX3- HDAC interaction will deepen our understanding of the functions of TBX3 and may also lead to the identification of a novel therapeutic target for breast cancer. ..
  28. Renu A Kowluru; Fiscal Year: 2016
    ..This will offer patients additional therapeutic means to prevent/retard the sight-threatening complication of diabetes. ..
  29. C/EBP, atrogin-1, and muscle wasting
    Per Olof Hasselgren; Fiscal Year: 2009
    ..Improved insight into mechanisms accounting for muscle wasting will help develop better treatments of this debilitating condition. ..
  30. Epigenetic regulation of liver transporters
    Frederick J Suchy; Fiscal Year: 2013
    ..or in addition, we predict that there will be active recruitment of potent repressor complexes composed of histone deacetylases and corepressor molecules to the promoters of most FXR-target genes...
  31. Developing Nrf2 as a target for treatment of corticosteroid resistance in COPD
    Robert A Wise; Fiscal Year: 2012
    ..This projects aims at preclinical development of a potential drug target that can be used in the clinical setting to improve steroid responsiveness in COPD nafients. ..
  32. The Effects of Ethanol on Microtubules during Mouse Pre-implantation Development
    Yixian Zheng; Fiscal Year: 2012
    ....
  33. Ludo Van Den Bosch; Fiscal Year: 2016
    ....
  34. The functions of the US3 protein kinase of herpes simplex virus
    Bernard Roizman; Fiscal Year: 2011
    ..5 in enabling the release of capsids from infected cells, (c) both US3 and US3.5 phosphorylate histone deacetylases 1 and 2 (HDAC-1/2) and enable the expression of genes introduced into cells by co-transduction (helper ..
  35. Carol A Fierke; Fiscal Year: 2016
    ..is regulated by competition between histone acetyltransferases, that catalyze protein N-acetylation, and histone deacetylases (HDACs), that catalyze hydrolysis of 5-N-acetyl lysine...
  36. Zheng Sun; Fiscal Year: 2014
    ..Together, these approaches will generate testable hypothesis backed up by preliminary data, which is essential for successful competition for future funding opportunities. ..
  37. Heat shock protein 90 antagonist-based therapy of mantle cell lymphoma
    Kapil Bhalla; Fiscal Year: 2012
    ..This strategy involves combinations of treatments with heat shock protein 90 and proteosome inhibitors designed to target protein folding and degradation in MCL cells. ..
  38. DIPAK KUMAR SARKAR; Fiscal Year: 2015
    ..research tests the hypothesis that alcohol's modulating effect on DNA methyltransferases and/or histone deacetylases makes an epigenetic mark on the D2 receptor gene that reduces D2 receptor production and its inhibitory ..
  39. Histone deacetylase 7 and its interacting proteins in endothelial cells
    Hung Ying Kao; Fiscal Year: 2013
    ..Understanding the signaling that control inflammation, proliferation, apoptosis, and angiogenesis may have therapeutic implication in treating vascular diseases. ..
  40. Energy Restrction and Mammary Cancer
    Henry J Thompson; Fiscal Year: 2013
    ....
  41. Role of Protein Acetylation in Ncx1 Expression
    Donald R Menick; Fiscal Year: 2012
    ..In this application, we will examine the role that histone deacetylases (HDAC) have in the regulation of Ncx1...
  42. Ting C Zhao; Fiscal Year: 2016
    ..Histone acetyltransferases (HAT) and histone deacetylases (HDAC) are enzymes that modify the expression of genes by regulating chromatin structure...
  43. Samir S El-Dahr; Fiscal Year: 2014
    ..We propose that replacement of the endogenous p53 gene with a non-phosphorytable version of p53 (p53S/A23) rescues HNF1[unreadable] expression and terminal differentiation in salt-stressed BdkrB2-/- embryos. ..
  44. Dietary HDAC Inhibitors in Colon Cancer Prevention
    Roderick H Dashwood; Fiscal Year: 2012
    ....
  45. Regulation of non-histone protein functions by histone deacetylases
    Edward Seto; Fiscal Year: 2010
    b>Histone deacetylases (HDACs) are enzymes that regulate the functions of histone proteins by catalyzing the removal of acetyl groups from lysine residues...
  46. GREGORY SCOTT SCHULTZ; Fiscal Year: 2014
    ....
  47. MARIA JOSE ALMEIDA; Fiscal Year: 2016
    ..Increased understanding of the mechanisms that control bone formation will provide important information for the development of therapies to maintain or increase bone mass and strength, thereby reducing the risk of osteoporotic fractures ..
  48. Shireen Saleque; Fiscal Year: 2014
    ..LSD1 (lysine specific demethylase1), CoREST/Rcor1 (REST co-repressor), other Rcor homologs and the histone deacetylases HDAC1-2, we propose to explore the role of these co-factors in establishing transcriptional and epigenetic ..
  49. The Role of The Histone Epigenome in the Pathophysiology of Endometriosis
    MARICARMEN COLON; Fiscal Year: 2012
    ..Histone modification, including deacetylation by histone deacetylases or HDACs, has recently emerged as a key mechanism of gene expression regulation in cancer and other ..
  50. Role of p62 in Protein Aggregation and Neurodegeneration in ALS
    Haining Zhu; Fiscal Year: 2009
    ..Purchase of necessary equipment, supplies and reagents for the proposed research will also stimulate the economy as intended by the American Recovery &Reinvestment Act. ..
  51. Hongxin Dong; Fiscal Year: 2014
    ..By advancing our understanding of the epigenetic mechanisms of drug efficacy, it will be possible to develop new psychotropic treatment strategies that maximize benefits while minimizing side effects. ..
  52. Craig E Crosson; Fiscal Year: 2014
    ..In this system, protein acetylation and deacetylation are catalyzed by histone acetyltransferases and by histone deacetylases (HDACs), respectively...
  53. Small Molecule-Mediated Augmentation of Kidney Regeneration
    Neil A Hukriede; Fiscal Year: 2010
    ..The purpose of these studies is to identify new HDACi analogues that have a high potential for moving to clinical trials. 1. ..
  54. Fu Shin X Yu; Fiscal Year: 2015
    ..abstract_text> ..
  55. Allan Tsung; Fiscal Year: 2016
    ..g. myocardial infarction and cerebral ischemia). ..
  56. Fengchun Ye; Fiscal Year: 2014
    ..Anaerobic gram- negative bacteria produce various short chain fatty acids (SCFAs) that inhibit class-1/2 histone deacetylases (HDACs) to promote histone hyperacetylation and viral gene expression...
  57. BRETT CAMERON LANGLEY; Fiscal Year: 2015
    ..Our findings in this project could lead to new treatments for spinal cord injury and other central nervous system injuries and disease. ..
  58. Small-molecule probes of chromatin-mediated neuroplasticity
    Stephen J Haggarty; Fiscal Year: 2013
    ..These multidisciplinary studies will shed new light on molecular mechanisms of brain plasticity and the relevance of these mechanisms to the development of novel therapeutics for their treatment of memory and mood disorders. ..
  59. Raju C Reddy; Fiscal Year: 2016
    ..It would also establish the feasibility of an innovative approach to restoring therapeutic glucocorticoid sensitivity, thereby promoting PPAR-g-glucocorticoid synergy, in COPD and potentially in other steroid-resistant diseases. ..
  60. Raul Mostoslavsky; Fiscal Year: 2014
    ....
  61. Characterization of a Novel Erythropoietin Signaling Pathway
    Adam N Goldfarb; Fiscal Year: 2013
    ..In this proposal, a new signaling pathway, that can potentially explain both the beneficial and deleterious effects of Epo, will be characterized. ..
  62. Repair of oxidative DNA damage in mammalian cells
    Tadahide Izumi; Fiscal Year: 2013
    ..abstract_text> ..
  63. CHUNG JEN JAMES J CHOU; Fiscal Year: 2016
    ..We will determine the efficacy of our lead HDAC6 inhibitor candidates against AML, performing pharmacokinetic and dynamic studies on lead inhibitor candidates, and validate the inhibitor's ability to influence biomarkers in vivo. ..
  64. DNA methylation in aging, race and prostate cancer
    Rajvir Dahiya; Fiscal Year: 2006
    ..This information can be used for better management of prostate cancer using DNA methylated genes as diagnostic or prognostic biomarkers. ..
  65. Histone Deacetylases and reversible acetylation in signaling and disease
    JOHN DENU; Fiscal Year: 2009
    ..This 2009 FASEB summer conference "Histone deacetylases and reversible acetylation in signaling and disease" will focus primarily on the biological pathways and ..
  66. Proteasome/HDAC Inhibition in Leukemia/MDS; Phase I Trial and Correlative Studies
    Steven Grant; Fiscal Year: 2010
    ....
  67. Inhibition of Autophagy: A Novel Therapeutic Strategy for Advanced Solid Tumors
    Francis J Giles; Fiscal Year: 2010
    ....
  68. Analyses of a Non tumorigenic Teratocarcinoma Cell Line
    Paulette McCormick; Fiscal Year: 2005
    ..These studies will contribute significantly to our understanding of stem cell biology, embryonic development and cancer. ..
  69. Phase I Trial of Bortezomib and Romidepsin in CLL and Small Cell Lymphoma
    Steven Grant; Fiscal Year: 2010
    ..This will position us to perform future trials that will determine the effectiveness of this novel drug combination in patients with CLL or SLL and address the validity of our preclinical pharmacodynamic observations. ..
  70. Signaling inputs that maintain the heterogeneity of colorectal cancer cells
    Darina Lazarova; Fiscal Year: 2010
    ..cells Abstract Butyrate, a fermentation product of dietary fiber in the colon, inhibits the activity of histone deacetylases and induces cell growth arrest, differentiation, and apoptosis in colorectal cancer (CRC) cells in vitro...
  71. Histone Deacetylase Inhibitors in CML
    Kapil Bhalla; Fiscal Year: 2009
    ..abstract_text> ..