Modulation of antigen-presenting cells by HDAC inhibitors: Implications in autoimmunity and cancer

Immunology and Cell Biology

Volumn 90, Issue 1, 2012, Pages 55-65

  Woan, Karrune V ^a   Sahakian, Eva ^a   Sotomayor, Eduardo M ^a   Seto, Edward ^a   Villagra, Alejandro ^a  

^a H LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE   (United States)

Author keywords

autoimmunity; HDAC; HDAC inhibitor

Indexed keywords

BELINOSTAT; CYCLOOXYGENASE 2; DEPSIPEPTIDE; ENTINOSTAT; GAMMA INTERFERON; GIVINOSTAT; HISTONE DEACETYLASE; HISTONE DEACETYLASE INHIBITOR; HLA A ANTIGEN; HLA B ANTIGEN; HLA C ANTIGEN; INTERLEUKIN 1; INTERLEUKIN 10; INTERLEUKIN 12; INTERLEUKIN 2; INTERLEUKIN 23; INTERLEUKIN 6; INTERLEUKIN 8; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 1; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 2; PANOBINOSTAT; ROMIDEPSIN; SIRTUIN; TEFINOSTAT; TRANSFORMING GROWTH FACTOR BETA; TRICHOSTATIN A; TUMOR NECROSIS FACTOR ALPHA; UNINDEXED DRUG; VALPROIC ACID; VORINOSTAT;

ADENOSINE DIPHOSPHATE RIBOSYLATION; ANTIGEN PRESENTING CELL; ANTIGEN RECOGNITION; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; AUTOIMMUNITY; CANCER CELL; CELL COMPARTMENTALIZATION; CELL DIFFERENTIATION; COMPLEMENT ACTIVATION; CYTOKINE PRODUCTION; DEPHOSPHORYLATION; DISEASE COURSE; DISEASE SEVERITY; DNA METHYLATION; DRUG EFFECT; ENDOPLASMIC RETICULUM; ENZYME ACTIVITY; ENZYME DEGRADATION; ENZYME INHIBITION; EPILEPSY; GENE CONTROL; GENE EXPRESSION; GENE LOCUS; GENETIC TRANSCRIPTION; HISTONE ACETYLATION; HISTONE MODIFICATION; HISTONE UBIQUITINATION; HUMAN; IMMUNE RESPONSE; IMMUNE SYSTEM; IMMUNOCOMPETENT CELL; IMMUNOMODULATION; IN VITRO STUDY; ISOMERIZATION; NEOPLASM; NONHUMAN; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PROTEIN CLEAVAGE; PROTEIN PHOSPHORYLATION; PROTEIN STABILITY; REVIEW; RNA SPLICING; SIGNAL TRANSDUCTION; SOMATIC CELL; TH1 CELL; TH2 CELL; TUMOR IMMUNITY; UPREGULATION;

ANTIGEN-PRESENTING CELLS; ANTINEOPLASTIC AGENTS; AUTOIMMUNITY; HISTONE DEACETYLASE INHIBITORS; HUMANS; IMMUNOLOGIC FACTORS; MODELS, IMMUNOLOGICAL; NEOPLASMS;

EID: 84855471028     PISSN: 08189641     EISSN: 14401711     Source Type: Journal    
DOI: 10.1038/icb.2011.96     Document Type: Review

References (135)

1. Luger K, Mader AW, Richmond RK, Sargent DF, Richmond TJ. Crystal structure of the nucleosome core particle at 2.8 A resolution. Nature 1997; 389: 251-260. (Pubitemid 27406632)
2. Suganuma T, Workman J. Signals and combinatorial functions of histone modifica-tions. Annu Rev Biochem 2011; 80: 27.
3. Bannister AJ, Kouzarides T. Regulation of chromatin by histone modifications. Cell Res 2011; 21: 381-395.
4. Lee KK, Workman JL. Histone acetyltransferase complexes: one size doesn't fit all. Nat Rev Mol Cell Biol 2007; 8: 284-295. (Pubitemid 46474661)
5. De Ruijter AJM, van Gennip AH, Caron HN, Kemp S, van Kuilenburg ABP. Histone deacetylases (HDACs): characterization of the classical HDAC family. Biochem J 2003; 370: 737-749. (Pubitemid 36399066)
6. Glozak MA, Sengupta N, Zhang X, Seto E. Acetylation and deacetylation of non-histoneproteins. Gene 2005; 363: 15-23.
7. Gu W, Roeder RG. Activation of p53 sequence-specific DNA binding by acetylation of the p53 C-terminal domain. Cell 1997; 90: 595-606. (Pubitemid 27357952)
8. Yuan Z-l, Guan Y-j, Chatterjee D, Chin YE. Stat3 dimerization regulated by reversible acetylation of a single lysine residue. Science 2005; 307: 269-273. (Pubitemid 40116244)
9. Boyes J, Byfield P, Nakatani Y, Ogryzko V Regulation of activity of the transcription factor GATA-1 byacetylation. Nature 1998; 396: 594-598. (Pubitemid 28563723)
10. Marzio G, Wagener C, Gutierrez MI, Cartwright P, Helin K, Giacca M. E2F family members are differentially regulated by reversible acetylation. J Biol Chem 2000; 275: 10887-10892. (Pubitemid 30212722)
11. Yao Y-L, Yang W-M, Seto E. Regulation of transcription factor YY1 by acetylation and deacetylation. Mol Cell Biol 2001; 21: 5979-5991. (Pubitemid 32737814)
12. Munshi N, Merika M, Yie J, Senger K, Chen G, Thanos D. Acetylation of HMG I(Y) by CBPturns off IFNß expression by disruptingthe enhanceosome. Mol Cell 1998; 2: 457-467. (Pubitemid 128381298)
13. Kiernan R, Brès V, Ng RWM, Coudart M-P, El Messaoudi S, Sardet C et al. Post-activation turn-off of NF-κB-dependent transcription is regulated by acetylation of p65. J Biol Chem 2003; 278: 2758-2766. (Pubitemid 36801357)
14. Kawai H, Li H, Avraham S, Jiang S, Avraham HK. Overexpression of histone deacetylase HDAC1 modulates breast cancer progression by negative regulation of estrogen receptor α. Int J Cancer 2003; 107: 353-358. (Pubitemid 37266453)
15. Gaughan L, Logan IR, Neal DE, Robson CN. Regulation of androgen receptor and histone deacetylase 1 by Mdm2-mediated ubiquitylation. Nucleic Acids Res 2005; 33: 13-26. (Pubitemid 40276925)
16. Martinez-Balbas MA, Bauer U-M, Nielsen SJ, Brehm A, Kouzarides T. Regulation of E2F1 activitybyacetylation. Embo J 2000; 19: 662-671.
17. Kovacs JJ, Murphy PJM, Gaillard S, Zhao X, Wu J-T, Nicchitta CV et al. HDAC6 regulates Hsp90 acetylation and chaperone-dependent activation of glucocorticoid receptor. Mol Cell 2005; 18: 601-607. (Pubitemid 40726236)
18. Hubbert C, Guardiola A, Shao R, Kawaguchi Y, Ito A, Nixon A et al. HDAC6 is a microtubule-associated deacetylase. Nature 2002; 417: 455-458. (Pubitemid 34563539)
19. Smith KT, Workman JL. Introducing the acetylome. Nat Biotechnol 2009; 27: 917-919.
20. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC et al. Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science 2009; 325: 834-840.
21. Leder A, Orkin S, Leder P. Differentiation of erythroleukemic cells in the presence of inhibitors of DNA synthesis. Science 1975; 190: 893-894.
22. Yoshida M, Kijima M, Akita M, Beppu T. Potent and specific inhibition of mammalian histonedeacetylase both in vivoand in vitrobytrichostatin A. JBiol Chem 1990; 265: 17174-17179.
23. Villagra A, Sotomayor EM, Seto E. Histone deacetylases and the immunological network: implications in cancer and inflammation. Oncogene 2010; 29: 157-173.
24. Kelly WK, O'Connor OA, Krug LM, Chiao JH, Heaney M, Curley Tet al. Phase I studyof anoral histonedeacetylase inhibitor, suberoylanilidehydroxamicacid, in patientswith advanced cancer. J Clin Oncol 2005; 23: 3923-3931.
25. Galli M, Salmoiraghi S, Golay J, Gozzini A, Crippa C, Pescosta N et al. A phase II multiple dose clinical trial of histone deacetylase inhibitor ITF2357 in patients with relapsed or progressive multiple myeloma. Ann Hematol 2010; 89: 185-190.
26. Roger T, Lugrin J, Le Roy D,Goy G, Mombelli M, Koessler Tet al. Histonedeacetylase inhibitors impair innate immune responses to Toll-like receptor agonists and to infection. Blood 2011; 117: 12.
27. Grabiec AM, Krausz S,de Jager W, Burakowski T,Groot D,Sanders MEet al.Histone deacetylase inhibitorssuppress inflammatoryactivation of rheumatoid arthritis patient synovial macrophages and tissue. J Immunol 2010; 184: 2718-2728.
28. Fuks F. DNA methylation and histone modifications: teaming upto silencegenes. Curr Opin Genet Dev 2005; 15: 490-495. (Pubitemid 41262404)
29. Marks PA, Breslow R. Dimethyl sulfoxide to vorinostat: development of this histone deacetylase inhibitor as an anticancer drug. Nat Biotech 2007; 25: 84-90. (Pubitemid 46087907)
30. Piekarz RL, Frye R, Turner M, Wright JJ, Allen SL, Kirschbaum MH et al. Phase II multi-institutional trial of the histone deacetylase inhibitor romidepsin as monotherapy for patients with cutaneous T-cell lymphoma. J Clin Oncol 2009; 27: 5410-5417.
31. Mandl-Weber S, Meinel FG, Jankowsky R, Oduncu F, Schmidmaier R, Baumann P. The novel inhibitor of histone deacetylase resminostat (RAS2410) inhibits proli-feration and induces apoptosis in multiple myeloma (MM) cells. Br J Haematol 2010; 149: 518-528.
32. Bolden JE, Peart MJ, Johnstone RW. Anticancer activities of histone deacetylase inhibitors. Nat Rev Drug Discov 2006; 5: 769-784. (Pubitemid 44348499)
33. Minucci S, Pelicci PG. Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer. Nat Rev Cancer 2006; 6: 38-51. (Pubitemid 43054973)
34. Dokmanovic M, Clarke C, Marks PA. Histone deacetylase inhibitors: overview and perspectives. Mol Cancer Res 2007; 5: 981.
35. Inoue S, Mai A, Dyer MJS, Cohen GM. Inhibition of histone deacetylase Class I but not Class II is critical for the sensitization of leukemic cells to tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis. Cancer Res 2006; 66: 6785-6792. (Pubitemid 44085638)
36. Aldana-Masangkay GI, Sakamoto KM. The role of HDAC6 in cancer. J Biomed Biotechnol 2010; 2011: 875824.
37. Buglio D, Khaskhely NM, Voo KS, Martinez-Valdez H, Liu Y-J, Younes A. HDAC11 plays an essential role in regulating OX40 ligand expression in Hodgkin lymphoma. Blood 2011; 117: 8.
38. Dunn GP, Old LJ, Schreiber RD. The immunobiology of cancer immunosurveillance and immunoediting. Immunity 2004; 21: 137-148. (Pubitemid 39094044)
39. O'Sullivan T, Dunn GP, Lacoursiere DY, Schreiber RD, Bui JD. Cancer immunoediting of the NK group 2D ligand H60a. J Immunol 2011; 187: 8.
40. Dunn GP, Bruce AT, Ikeda H, Old LJ, Schreiber RD. Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol 2002; 3: 991-998. (Pubitemid 35363648)
41. Khong HT, Restifo NP. Natural selection of tumor variants in thegeneration of "tumor escape" phenotypes. Nat Immunol 2002; 3: 999-1005. (Pubitemid 35363649)
42. Setiadi AF, Omilusik K, David MD, Seipp RP, Hartikainen J, Gopaul R et al. Epigenetic enhancement of antigen processing and presentation promotes immune recognition of tumors. Cancer Res 2008; 68: 9601-9607.
43. Murakami T, Sato A, Chun NA, Hara M, Naito Y, Kobayashi Y et al. Transcriptional modulation using HDACi depsipeptide promotes immune cell-mediated tumor destruction of murine B16 melanoma. J Invest Dermatol 2008; 128: 1506-1516. (Pubitemid 351693204)
44. Vo DD, Prins RM, Begley JL, Donahue TR, Morris LF, Bruhn KW et al. Enhanced antitumoractivity induced byadoptive T-cell transferand adjunctiveuseofthehistone deacetylase inhibitor LAQ824. Cancer Res 2009; 69: 8693-8699.
45. Christiansen AJ, West A, Banks K-M, Haynes NM, Teng MW, Smyth MJ et al. Eradication of solid tumors using histone deacetylase inhibitors combined with immune-stimulating antibodies. Proc Natl Acad Sci USA 2011; 108: 6.
46. Koenen HJ, Smeets RL, Vink PM, van Rijssen E, Boots AM, Joosten I. Human CD25high Foxp3pos regulatory T cells differentiate into IL-17-producing cells. Blood 2008; 112: 2340-2352.
47. Reddy P, Sun Y, Toubai T, Duran-Struuck R, Clouthier SG, Weisiger E et al. Histone deacetylase inhibition modulates indoleamine 2,3-dioxygenase- dependent DC func-tions and regulates experimental graft-versus-host disease in mice. J Clin Invest 2008;118: 2562-2573. (Pubitemid 351949783)
48. Shapira Y, Agmon-Levin N, Shoenfeld Y. Definingand analyzinggeoepidemiologyand human autoimmunity. J Autoimmun 2010; 34: J168-J177.
49. Szyf M. Epigenetic therapeutics in autoimmune disease. Clin Rev Allergy Immunol 2010; 39: 62-77.
50. Grabiec AM, Reedquist KA. Histone deacetylases in RA: epigenetics and epipheno-mena. Arthritis Res Ther 2010; 12: 142.
51. Leoni F, Fossati G, Lewis EC, Lee JK, Porro G, Pagani Pet al.The hist one deacety lase inhibitor ITF2357 reduces production of pro-inflammatory cytokines in vitro and systemic inflammation in vivo. Mol Med 2005; 11: 1-15.
52. Vojinovic J, Damjanov N. HDAC inhibition in rheumatoid arthritis and juvenile idiopathic arthritis. Mol Med 2011; 17: 397-403.
53. Reilly CM, Regna N, Mishra N. HDAC inhibition in lupus models. Mol Med 2011; 17: 417-425.
54. Marwick JA, Ito K, Adcock IM, Kirkham PA. Oxidative stress and steroid resistance in asthma and COPD: pharmacological manipulation of HDAC-2 as a therapeutic strategy. Expert Opin Ther Targets 2007; 11: 745-755. (Pubitemid 46901395)
55. Mastronardi FG, Noor A, Wood DD, Paton T, Moscarello MA. Peptidyl argininedeimi-nase 2 Cp G island in multiple sclerosis white matter is hypomethylated. J Neurosci Res 2007; 85: 2006-2016. (Pubitemid 47051489)
56. Qi Q, Guo Q, Tan G, Mao Y, Tang H, Zhou C et al. Predictors of the scleroderma phenotype in fibroblasts from systemic sclerosis patients. J Eur Acad Dermatol Venereol 2009; 23: 160-168.
57. Zhang K, Zhang R, Li X, Yin G, Niu X. Promoter methylation status of p15 and p21 genes in HPP-CFCs of bone marrowof patients with psoriasis. Eur J Dermatol 2009; 19: 141-146.
58. Glauben R, Siegmund B. Inhibition of histone deacetylases in inflammatory bowel diseases. Mol Med 2011; 17: 426-433.
59. Consalvi S, Saccone V, Giordani L, Minetti G, Mozzetta C, Puri PL. Histonedeacety-lase inhibitors in the treatment of muscular dystrophies: epigenetic drugs for genetic diseases. Mol Med 2011; 17: 457-465.
60. D'Cruz DP, Khamashta MA, Hughes GR. Systemic lupus erythematosus. Lancet 2007; 369: 587-596. (Pubitemid 46241445)
61. Rahman A, Isenberg DA. Systemic lupus erythematosus. N Engl J Med 2008; 358: 929-939. (Pubitemid 351397092)
62. Moser KL, Kelly JA, Lessard CJ, Harley JB. Recent insights into the genetic basis of systemic lupus erythematosus. Genes Immun 2009; 10: 373-379.
63. Mishra N, Brown DR, Olorenshaw IM, Kammer GM. Trichostatin A reverses skewed expression of CD154, interleukin-10, and interferon-gamma geneand protein expres-sion in lupus Tcells. Proc Natl Acad Sci USA 2001; 98: 2628-2633. (Pubitemid 32209533)
64. Chung YL, Lee MY, Wang AJ, Yao LF. A therapeutic strategy uses histone deacetylase inhibitors to modulate the expression of genes involved in the pathogenesis of rheumatoid arthritis. Mol Ther 2003; 8: 707-717.
65. Maciejewska Rodrigues H, Jungel A, Gay RE, Gay S. Innate immunity, epigeneticsand autoimmunity in rheumatoid arthritis. Mol Immunol 2009; 47: 12-18.
66. Wang H, Cheng F, Woan K, Sahakian E, Merino O, Rock-Klotz J et al. Histone deacetylase inhibitor LAQ824 augments inflammatory responses in macrophages through transcriptional regulation of IL-10. JImmunol 2011; 186: 11.
67. Van den Elsen PJ, Peijnenburg A, van Eggermond MC, Gobin SJ. Shared regulatory elements in the promoters of MHC class I and class II genes. Immunol Today 1998; 19: 308-312. (Pubitemid 28322326)
68. Gobin SJ, Peijnenburg A, Keijsers V, van den Elsen PJ. Site alpha is crucial for two routes of IFN gamma-induced MHC class I transactivation: the ISRE-mediated route and a novel pathway involving CIITA. Immunity 1997; 6: 601-611. (Pubitemid 27239351)
69. Ackerman AL, Cresswell P. Cellular mechanisms governing cross-presentation of exogenous antigens. Nat Immunol 2004; 5: 678-684. (Pubitemid 39023296)
70. Khan AN, Magner WJ, Tomasi TB. An epigenetic vaccine model active in the prevention and treatment of melanoma. J Transl Med 2007; 5: 64.
71. Khan AN, Gregorie CJ, Tomasi TB. Histone deacetylase inhibitors induce TAP, LMP, Tapasin genes and MHC class I antigen presentation by melanoma cells. Cancer Immunol Immunother 2008; 57: 647-654.
72. Pellicciotta I,Cortez-Gonzalez X,Sasik R, Reiter Y, Hardiman G, Langlade-Demoyen P et al. Presentation of telomerase reversetranscriptase, a self-tumor antigen, is down-regulated by histone deacetylase inhibition. Cancer Res 2008; 68: 8085-8093.
73. Song W, Tai YT, Tian Z, Hideshima T, Chauhan D, Nanjappa P et al. HDAC inhibition by LBH589 affects the phenotype and function of human myeloid dendritic cells. Leukemia 2011; 25: 161-168.
74. Cho H-I, Lee Y-R, Celis E. Interferon γ limitsthe effectiveness of melanoma peptide vaccines. Blood 2011; 117: 135-144.
75. Khan A, Tomasi T. Histonedeacetylaseregulationof immunegeneexpression in tumor cells. Immunol Res 2008; 40: 164-178.
76. Lazaro E, Kadie C, Stamegna P, Zhang SC, Gourdain P, Lai NY et al. Variable HIV peptide stability in human cytosol is critical to epitope presentation and immune escape. JClin Invest 2011; 121: 2480-2492.
77. Zika E, Greer SF, Zhu XS, Ting JP. Histone deacetylase 1/m Sin3A disrupts gamma interferon-induced CIITA function and major histocompatibility complex class II enhanceosomeformation. Mol Cell Biol 2003; 23: 3091-3102. (Pubitemid 36459224)
78. Kong X, Fang M, Li P, Fang F, Xu Y HDAC2 deacetylates class II transactivator and suppresses its activity in macrophages and smooth muscle cells. J Mol Cell Cardiol 2009; 46: 292-299.
79. Tomasi TB, Magner WJ, Khan AN. Epigenetic regulation of immune escape genes in cancer. Cancer Immunol Immunother 2006; 55: 1159-1184. (Pubitemid 43992044)
80. Reith W, Leibund Gut-Landmann S, Waldburger J-M. Regulation of MHC class II gene expression by the class II transactivator. Nat Rev Immunol 2005; 5: 793-806. (Pubitemid 41400853)
81. Soos JM, Krieger JI, Stuve O, King CL, Patarroyo JC, Aldape K et al. Malignant glioma cells use MHC class II transactivator (CIITA) promoters III and IV to direct IFN-gamma-inducible CIITA expression and can function as nonprofessional antigen presenting cells in endocytic processing and CD4(+) T-cell activation. Glia 2001; 36: 391-405. (Pubitemid 34010066)
82. Shakespear MR, Halili MA, Irvine KM, Fairlie DP, Sweet MJ. Histonedeacetylases as regulators of inflammation and immunity. Trends Immunol 2011; 32: 335-343.
83. Chou SD, Khan AN, Magner WJ,Tomasi TB. Histoneacetylation regulates the cell type specific CIITA promoters, MHC class II expression and antigen presentation in tumor cells. Int Immunol 2005; 17: 1483-1494. (Pubitemid 41631324)
84. Gialitakis M, Kretsovali A, Spilianakis C, Kravariti L, Mages J, Hoffmann R et al. Coordinated changes of histone modifications and HDAC mobilization regulate the induction of MHC class II genes by Trichostatin A. Nucleic Acids Res 2006; 34: 765-772. (Pubitemid 43380662)
85. Martin BK, Frelinger JG, Ting JP. Combination genetherapywith CD86 and the MHC class II transactivator in the control of lung tumor growth. J Immunol 1999; 162: 6663-6670. (Pubitemid 29309391)
86. Serrador JM, Cabrero JR, Sancho D, Mittelbrunn M, Urzainqui A, Sanchez-Madrid F. HDAC6 deacetylase activity links the tubulin cytoskeleton with immune synapse organization. Immunity 2004; 20: 417-428. (Pubitemid 38482120)
87. Säemann MD, Böhmig GA, Österreicher CH, Burtscher H, Parolini O, Diakos C et al. Anti-inflammatory effects of sodium butyrate on human monocytes: potent inhibition of IL-12 and up-regulation of IL-10 production. FASEBJ 2000; 14: 3.
88. Bode KA, Schroder K, Hume DA, Ravasi T, Heeg K, Sweet MJ et al. Histone deacetylase inhibitors decrease Toll-like receptor-mediated activation of proinflamma-torygeneexpression by impairingtranscription factor recruitment. Immunology 2007; 122: 596-606. (Pubitemid 350075958)
89. Trinchieri G. Interleukin-12 and the regulation of innate resistance and adaptive immunity. Nat Rev Immunol 2003; 3: 133-146. (Pubitemid 37328691)
90. Chang H-M, Paulson M, Holko M, Rice CM, Williams BRG, Marié I et al. Induction of interferon-stimulated gene expression and antiviral responses require protein deace-tylase activity. Proc Natl Acad Sci USA 2004; 101: 6.
91. Axtell RC, Raman C, Steinman L. Interferon-ß exacerbates Th17-mediated inflam-matorydisease. Trends Immunol 2011; 32: 272-277.
92. Nusinzon I, Horvath CM. Positive and Negative Regulation of the Innate Antiviral Response and Beta Interferon Gene Expression by Deacetylation. Mol Cell Biol 2006; 26: 3106-3113.
93. Villagra A, Cheng F, Wang HW, Suarez I, Glozak M, Maurin M et al. The histone deacetylase HDAC11 regulates the expression of interleukin 10 and immune toler-ance. Nat Immunol 2009; 10: 92-100.
94. Chen L, Fischle W, Verdin E, Greene WC. Duration of nuclear NF-kappa B action regulated by reversible acetylation. Science 2001; 293: 1653-1657. (Pubitemid 32807844)
95. Place RF, Noonan EJ, Giardina C. HDAC inhibition prevents NF-κB activation by suppressing proteasome activity: down-regulation of proteasome subunit expression stabilizes I?Bα. Biochem Pharmacol 2005; 70: 394-406 (Pubitemid 40905111)
96. Darnell JE.Validating Stat3 incancertherapy Nat Med 2005; 11: 595-596.
97. Cheng F, Wang HW, Cuenca A, Huang M, Ghansah T, Brayer J et al. A critical role for Stat3 signaling in immunetolerance. Immunity 2003; 19: 425-436. (Pubitemid 37153418)
98. Togi S, Kamitani S, Kawakami S, Ikeda O, Muromoto R, Nanbo A et al. HDAC3 influencesphosphorylation of STAT3 atserine 727 by interactingwith PP2A. Biochem Biophys Res Commun 2009; 379: 616-620.
99. Weinstein IB. Addiction to oncogenes-the Achilles heal of cancer. Science 2002; 297: 63-64. (Pubitemid 34743088)
100. Reddy P, Maeda Y, Hotary K, Liu C, Reznikov LL, Dinarello CA et al. Histone deacetylase inhibitor suberoylanilide hydroxamic acid reduces acute graft-versus-host disease and preserves graft-versus-leukemia effect. Proc Natl Acad Sci USA 2004; 101: 3921-3926. (Pubitemid 38381078)
101. Lagger G, O'Carroll D, Rembold M, Khier H, Tischler J, Weitzer G. Essential function of histonedeacetylase 1 in proliferation control and CDK inhibitor repression. EMBO J 2002; 21: 2672-2681. (Pubitemid 34619383)
102. Kawabata T, Nishida K, Takasugi K, Ogawa H, Sada K, Kadota Y et al. Increased activity and expression of histone deacetylase 1 in relation to tumor necrosis factor-alpha in synovial tissue of rheumatoid arthritis. Arthritis Res Ther 2010; 12: R133.
103. Faraco G, Cavone L, Chiarugi A. The therapeutic potential of HDAC inhibitors in the treatmentofmultiplesclerosis. Mol Med 2011; 17: 442-447.
104. Enya K, Hayashi H, Takii T, Ohoka N, Kanata S, Okamoto Tet al. The interaction with Sp1 and reduction in the activity of histone deacetylase 1 are critical for the constitutive gene expression of IL-1{alpha} in human melanoma cells. J Leukoc Biol 2008;83: 190-199.
105. Wang J, Lee S, Teh CE-Y, Bunting K, Ma L, Shannon MF. The transcription repressor, ZEB1, cooperateswith Ct BP2 and HDAC1 to suppress IL-2 geneactivation in Tcells. Int Immunol 2009; 21: 227-235.
106. Lu J, Sun H, Wang X, Liu C, Xu X, Li F et al. Interleukin-12 p40 promoter activity is regulated by the reversible acetylation mediated by HDAC1 and p300. Cytokine 2005; 31: 46-51. (Pubitemid 40828358)
107. Jee Y-K, Gilmour J, Kelly A, Bowen H, Richards D, Soh C et al. Repression of interleukin-5 transcription by the glucocorticoid receptor targets GATA3 signaling and involves histone deacetylase recruitment. J Biol Chem 2005; 280: 23243-23250. (Pubitemid 40853236)
108. Chang S, Collins PL, Aune TM. T-bet dependent removal of Sin3A-histone deacety-lase complexes at the Ifng locus drives Th1 differentiation. J Immunol 2008; 181: 8372-8381.
109. Valapour M, Jia G, John TS, Judith K, Antonella C, Vincenzo C et al. Histone deacetylation inhibits IL4 gene expression in T cells. J Allergy Clin Immunol 2002; 109: 238-245. (Pubitemid 34158287)
110. Xu M, Nie L, Kim SH, Sun XH. STAT5-induced Id-1 transcription involves recruitment of HDAC1 and deacetylation of C/EBPbeta. Embo J 2003; 22: 893-904. (Pubitemid 36227791)
111. Kato N, Tanaka J, Sugita J, Toubai T, Miura Y, Ibata M et al. Regulation of the expression of MHC class I-related chain A, B (MICA, MICB) via chromatin remodeling and its impact on the susceptibility of leukemic cells to the cytotoxicity of NKG2D-expressingcells. Leukemia 2007; 21: 2103-2108. (Pubitemid 47423800)
112. Bressi JC, Jennings AJ, Skene R, Wu Y, Melkus R, De Jong R et al. Exploration of the HDAC2 foot pocket: synthesis and SAR ofsubstituted N-(2-aminophenyl)benzamides. Bioorg Med Chem Lett 2010; 20: 4.
113. Montgomery RL, Davis CA, Potthoff MJ, Haberland M, Fielitz J,Qi Xet al. Histone deacetylases 1 and 2 redundantly regulate cardiac morphogenesis, growth, and contractility. Genes Dev 2007; 21: 1790-1802. (Pubitemid 47076478)
114. Huber LC, Brock M, Hemmatazad H, Giger OT, Moritz F, Trenkmann M et al. Histone deacetylase/acetylase activity in total synovial tissue derived from rheumatoid arthritis and osteoarthritis patients. Arthritis Rheum 2007; 56: 1087-1093. (Pubitemid 46608633)
115. Minetti GC, Colussi C, Adami R, Serra C, Mozzetta C, Parente V et al. Functional and morphological recovery of dystrophic muscles in mice treated with deacetylase inhibitors. Nat Med 2006; 12: 1147-1150. (Pubitemid 44527349)
116. Ito K, Barnes PJ, Adcock IM. Glucocorticoid receptor recruitment of histone deace-tylase 2 inhibits interleukin-1beta -induced histone H4 acetylation on lysines 8 and 12. Mol Cell Biol 2000; 20: 6891-6903.
117. Bhaskara S, Chyla BJ, Amann JM, Knutson SK, Cortez D, Sun Z-W et al. Deletion of histone deacetylase 3 reveals critical roles in S phase progression and DNA damage control. Mol Cell 2008; 30: 61-72. (Pubitemid 351470157)
118. Kuwatsuka Y, Ogawa F, Iwata Y, Komura K, Muroi E, Hara T et al. Decreased levels of autoantibody against histone deacetylase 3 in patients with systemic sclerosis. Autoimmunity 2009; 42: 120-125.
119. Zhang Y, Tuzova M, Xiao Z-XJ, Cruikshank WW, Center DM. Pro-IL-16 recruits histone deacetylase 3 to the Skp2 core promoter through interaction with transcription factor GABP. JImmunol 2008; 180: 402-408.
120. Krãmer OH, Knauer SK, Greiner G, Jandt E, Reichardt S, Gãhrs K-H et al. A phosphorylation-acetylation switch regulates STAT1 signaling. Genes Dev 2009; 23: 223-235.
121. Watamoto K, Towatari M, Ozawa Y, Miyata Y, Okamoto M, Abe A et al. Altered interaction of HDAC5 with GATA-1 during MEL cell differentiation. Oncogene 2003; 22: 9176-9184. (Pubitemid 38067993)
122. Ozawa Y, Towatari M, Tsuzuki S, Hayakawa F, Maeda T, Miyata Y et al. Histone deacetylase 3 associates with and represses the transcription factor GATA-2. Blood 2001; 98: 2116-2123.
123. Chen G-Y, Osada H, Santamaria-Babi LF, Kannagi R. Interaction of GATA-3/T-bet transcription factors regulates expression of sialyl Lewis X homing receptors on Th1/ Th2 lymphocytes. Proc Natl Acad Sci USA 2006; 103: 6.
124. Vannini A, Volpari C, Gallinari P, Jones P, Mattu M, Carfi A et al. Substrate bindingto histone deacetylases as shown by the crystal structure of the HDAC8-substrate complex. EMBO Rep 2007; 8: 879-884. (Pubitemid 350001433)
125. Haberland M, Mokalled MH, Montgomery RL, Olson EN. Epigenetic control of skull morphogenesis by histone deacetylase 8. Genes Dev 2009; 23: 1625-1630.
126. Bottomley MJ. Structures of protein domains that create or recognize histone modifications. EMBO Rep 2004; 5: 464.
127. Vega RB, Matsuda K,Oh J, Barbosa AC, Yang X, Meadows E et al. Histonedeacetylase 4 control schondrocyte hypertrophy durings keletogenesis. Cell 2004; 119: 555-566.
128. Sun Y, Ge Y, Drnevich J, Zhao Y, Band M, Chen J. Mammalian target of rapamycin regulates mi RNA-1 and follistatin in skelet al myogenesis. J Cell Biol 2010; 189: 1157-1169.
129. Chang S, Mc Kinsey TA, Zhang CL, Richardson JA, Hill JA, Olson EN. Histone deacetylases 5 and 9 govern responsiveness of the heart to a subset of stress signals and play redundant roles in heart development. Mol Cell Biol 2004; 24: 8467-8476. (Pubitemid 39245069)
130. Schmeck B, Lorenz J, N'Guessan PD, Opitz B, van Laak V, Zahlten J et al. Histone acetylation and flagellin are essential for Legionella pneumophila-induced cytokine expression. JImmunol 2008; 181: 940-947.
131. Schuetz A, Min J, Allali-Hassani A, Schapira M, Shuen M, Loppnau P et al. Human HDAC7 harborsa class IIa histonedeacetylase-specific zinc binding motifand cryptic deacetylase activity. J Biol Chem 2008; 283: 11355-11363.
132. Chang S, Young BD, Li S, Qi X, Richardson JA, Olson EN. Histone deacetylase 7 maintains vascular integrity by repressing matrix met alloproteinase 10. Cell 2006; 126:321-334. (Pubitemid 44092958)
133. Li B, Samanta A, Song X, Iacono KT, Bembas K, Tao R et al. FOXP3 interactionswith histoneacetyltransferaseand class II histonedeacetylasesare required for repression. Proc Natl Acad Sci USA 2007; 104: 6.
134. Zhang CL, Mc Kinsey TA, Chang S, Antos CL, Hill JA, Olson EN. Class II histone deacetylases act as signal-responsive repressors of cardiac hypertrophy. Cell 2002; 110:479-488. (Pubitemid 35232291)
135. Zhang Y, Kwon S, Yamaguchi T, Cubizolles F, Rousseaux S, Kneissel M et al. Mice lacking histonedeacetylase 6 have hyperacetylated tubulin but areviableand develop normally. Mol Cell Biol 2008; 28: 1688-1701.