Histone Deacetylase 6 in Health and Disease

References

• Marmorstein R , RothSY . Histone acetyltransferases: function, structure, and catalysis . Curr. Opin. Genet. Dev.11 ( 2 ), 155 – 161 ( 2001 ).
   PubMed Web of Science ®Google Scholar
• De Ruijter AJ , Van GennipAH , CaronHN , KempS , Van KuilenburgAB . Histone deacetylases (HDACs): characterization of the classical HDAC family . Biochem. J.370 ( Pt 3 ), 737 – 749 ( 2003 ).
   PubMed Web of Science ®Google Scholar
• Aldana-Masangkay GI , SakamotoKM . The role of HDAC6 in cancer . J. Biomed. Biotechnol.2011 , 875824 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Bertos NR , GilquinB , ChanGK , YenTJ , KhochbinS , YangXJ . Role of the tetradecapeptide repeat domain of human histone deacetylase 6 in cytoplasmic retention . J. Biol. Chem.279 ( 46 ), 48246 – 48254 ( 2004 ).
   PubMed Web of Science ®Google Scholar
• Seigneurin-Berny D , VerdelA , CurtetSet al. Identification of components of the murine histone deacetylase 6 complex: link between acetylation and ubiquitination signaling pathways . Mol. Cell. Biol.21 ( 23 ), 8035 – 8044 ( 2001 ).
   PubMed Web of Science ®Google Scholar
• Pugacheva EN , JablonskiSA , HartmanTR , HenskeEP , GolemisEA . HEF1-dependent Aurora A activation induces disassembly of the primary cilium . Cell129 ( 7 ), 1351 – 1363 ( 2007 ).
   PubMed Web of Science ®Google Scholar
• Williams KA , ZhangM , XiangSet al. Extracellular signal-regulated kinase (ERK) phosphorylates histone deacetylase 6 (HDAC6) at serine 1035 to stimulate cell migration . J. Biol. Chem.288 ( 46 ), 33156 – 33170 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Han Y , JeongHM , JinYHet al. Acetylation of histone deacetylase 6 by p300 attenuates its deacetylase activity . Biochem. Biophys. Res. Commun.383 ( 1 ), 88 – 92 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Hook SS , OrianA , CowleySM , EisenmanRN . Histone deacetylase 6 binds polyubiquitin through its zinc finger (PAZ domain) and copurifies with deubiquitinating enzymes . Proc. Natl Acad. Sci. USA99 ( 21 ), 13425 – 13430 ( 2002 ).
   PubMed Web of Science ®Google Scholar
• Liu Y , PengL , SetoE , HuangS , QiuY . Modulation of histone deacetylase 6 (HDAC6) nuclear import and tubulin deacetylase activity through acetylation . J. Biol. Chem.287 ( 34 ), 29168 – 29174 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Chen PB , HungJH , HickmanTLet al. Hdac6 regulates Tip60-p400 function in stem cells . eLife2 , e01557 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Verdel A , CurtetS , BrocardMPet al. Active maintenance of mHDA2/mHDAC6 histone-deacetylase in the cytoplasm . Curr. Biol.10 ( 12 ), 747 – 749 ( 2000 ).
   PubMed Web of Science ®Google Scholar
• Voelter-Mahlknecht S , MahlknechtU . Cloning and structural characterization of the human histone deacetylase 6 gene . Int. J. Mol. Med.12 ( 1 ), 87 – 93 ( 2003 ).
   PubMed Web of Science ®Google Scholar
• Ding G , LiuHD , HuangQet al. HDAC6 promotes hepatocellular carcinoma progression by inhibiting P53 transcriptional activity . FEBS Lett.587 ( 7 ), 880 – 886 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Lam HC , CloonanSM , BhashyamARet al. Histone deacetylase 6-mediated selective autophagy regulates COPD-associated cilia dysfunction . J. Clin. Invest.123 ( 12 ), 5212 – 5230 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Zhuang Y , NguyenHT , LaskyJAet al. Requirement of a novel splicing variant of human histone deacetylase 6 for TGF-beta1-mediated gene activation . Biochem. Biophys. Res. Commun.392 ( 4 ), 608 – 613 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• Lwin T , ZhaoX , ChengFet al. A microenvironment-mediated c-Myc/miR-548m/HDAC6 amplification loop in non-Hodgkin B cell lymphomas . J. Clin. Invest.123 ( 11 ), 4612 – 4626 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Huang S , WangS , BianCet al. Upregulation of miR-22 promotes osteogenic differentiation and inhibits adipogenic differentiation of human adipose tissue-derived mesenchymal stem cells by repressing HDAC6 protein expression . Stem Cells Dev.21 ( 13 ), 2531 – 2540 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Simon D , LalooB , BarillotMet al. A mutation in the 3’-UTR of the HDAC6 gene abolishing the post-transcriptional regulation mediated by hsa-miR-433 is linked to a new form of dominant X-linked chondrodysplasia . Hum. Mol. Genet.19 ( 10 ), 2015 – 2027 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• Conacci-Sorrell M , NgouenetC , EisenmanRN . Myc-nick: a cytoplasmic cleavage product of Myc that promotes alpha-tubulin acetylation and cell differentiation . Cell142 ( 3 ), 480 – 493 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• Creppe C , MalinouskayaL , VolvertMLet al. Elongator controls the migration and differentiation of cortical neurons through acetylation of alpha-tubulin . Cell136 ( 3 ), 551 – 564 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• L’hernault SW , RosenbaumJL . Chlamydomonas alpha-tubulin is posttranslationally modified in the flagella during flagellar assembly . J. Cell Biol.97 ( 1 ), 258 – 263 ( 1983 ).
   PubMed Web of Science ®Google Scholar
• Ohkawa N , SugisakiS , TokunagaEet al. N-acetyltransferase ARD1-NAT1 regulates neuronal dendritic development . Genes Cells13 ( 11 ), 1171 – 1183 ( 2008 ).
   PubMed Web of Science ®Google Scholar
• Hubbert C , GuardiolaA , ShaoRet al. HDAC6 is a microtubule-associated deacetylase . Nature417 ( 6887 ), 455 – 458 ( 2002 ).
   PubMed Web of Science ®Google Scholar
• North BJ , MarshallBL , BorraMT , DenuJM , VerdinE . The human Sir2 ortholog, SIRT2, is an NAD+-dependent tubulin deacetylase . Mol. Cell.11 ( 2 ), 437 – 444 ( 2003 ).
   PubMed Web of Science ®Google Scholar
• Zhang X , YuanZ , ZhangYet al. HDAC6 modulates cell motility by altering the acetylation level of cortactin . Mol. Cell.27 ( 2 ), 197 – 213 ( 2007 ).
   PubMed Web of Science ®Google Scholar
• Zhang Y , ZhangM , DongHet al. Deacetylation of cortactin by SIRT1 promotes cell migration . Oncogene28 ( 3 ), 445 – 460 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Lee JY , KogaH , KawaguchiYet al. HDAC6 controls autophagosome maturation essential for ubiquitin-selective quality-control autophagy . EMBO J.29 ( 5 ), 969 – 980 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• Ouyang H , AliYO , RavichandranMet al. Protein aggregates are recruited to aggresome by histone deacetylase 6 via unanchored ubiquitin C termini . J. Biol. Chem.287 ( 4 ), 2317 – 2327 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Watabe M , NakakiT . Protein kinase CK2 regulates the formation and clearance of aggresomes in response to stress . J. Cell Sci.124 ( Pt 9 ), 1519 – 1532 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Liu KP , ZhouD , OuyangDYet al. LC3B-II deacetylation by histone deacetylase 6 is involved in serum-starvation-induced autophagic degradation . Biochem. Biophys. Res. Commun.441 ( 4 ), 970 – 975 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• An WG , SchulteTW , NeckersLM . The heat shock protein 90 antagonist geldanamycin alters chaperone association with p210bcr-abl and v-src proteins before their degradation by the proteasome . Cell Growth Differ.11 ( 7 ), 355 – 360 ( 2000 ).
   PubMedGoogle Scholar
• Renoir JM , RadanyiC , FaberLE , BaulieuEE . The non-DNA-binding heterooligomeric form of mammalian steroid hormone receptors contains a hsp90-bound 59-kilodalton protein . J. Biol. Chem.265 ( 18 ), 10740 – 10745 ( 1990 ).
   PubMed Web of Science ®Google Scholar
• Sanchez ER , MeshinchiS , TienrungrojW , SchlesingerMJ , ToftDO , PrattWB . Relationship of the 90-kDa murine heat shock protein to the untransformed and transformed states of the L cell glucocorticoid receptor . J. Biol. Chem.262 ( 15 ), 6986 – 6991 ( 1987 ).
   PubMed Web of Science ®Google Scholar
• Boyault C , GilquinB , ZhangYet al. HDAC6-p97/VCP controlled polyubiquitin chain turnover . EMBO J.25 ( 14 ), 3357 – 3366 ( 2006 ).
   PubMed Web of Science ®Google Scholar
• Lee JY , NaganoY , TaylorJP , LimKL , YaoTP . Disease-causing mutations in parkin impair mitochondrial ubiquitination, aggregation, and HDAC6-dependent mitophagy . J. Cell Biol.189 ( 4 ), 671 – 679 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• Rao R , FiskusW , YangYet al. HDAC6 inhibition enhances 17-AAG‐‐mediated abrogation of hsp90 chaperone function in human leukemia cells . Blood112 ( 5 ), 1886 – 1893 ( 2008 ).
   PubMed Web of Science ®Google Scholar
• Deribe YL , WildP , ChandrashakerAet al. Regulation of epidermal growth factor receptor trafficking by lysine deacetylase HDAC6 . Sci. Signal2 ( 102 ), ra84 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Gao YS , HubbertCC , LuJ , LeeYS , LeeJY , YaoTP . Histone deacetylase 6 regulates growth factor-induced actin remodeling and endocytosis . Mol. Cell. Biol.27 ( 24 ), 8637 – 8647 ( 2007 ).
   PubMed Web of Science ®Google Scholar
• ian C , JarzembowskiJA , OpipariAW , Jr. , CastleVP , KwokRP . HDAC6 deacetylates Ku70 and regulates Ku70-Bax binding in neuroblastoma . Neoplasia13 ( 8 ), 726 – 734 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Kerr E , HolohanC , MclaughlinKMet al. Identification of an acetylation-dependant Ku70/FLIP complex that regulates FLIP expression and HDAC inhibitor-induced apoptosis . Cell Death Differ.19 ( 8 ), 1317 – 1327 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Lee YS , LimKH , GuoXet al. The cytoplasmic deacetylase HDAC6 is required for efficient oncogenic tumorigenesis . Cancer Res.68 ( 18 ), 7561 – 7569 ( 2008 ).
   PubMed Web of Science ®Google Scholar
• Chen CS , WengSC , TsengPH , LinHP , ChenCS . Histone acetylation-independent effect of histone deacetylase inhibitors on Akt through the reshuffling of protein phosphatase 1 complexes . J. Biol. Chem.280 ( 46 ), 38879 – 38887 ( 2005 ).
   PubMed Web of Science ®Google Scholar
• Kim IA , NoM , LeeJMet al. Epigenetic modulation of radiation response in human cancer cells with activated EGFR or HER-2 signaling: potential role of histone deacetylase 6 . Radiother. Oncol.92 ( 1 ), 125 – 132 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Tien SC , ChangZF . Oncogenic Shp2 disturbs microtubule regulation to cause HDAC6-dependent ERK hyperactivation . Oncogene33 ( 22 ), 2938 – 2946 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Zhu QY , WangZ , JiCet al. C6-ceramide synergistically potentiates the anti-tumor effects of histone deacetylase inhibitors via AKT dephosphorylation and alpha-tubulin hyperacetylation both in vitro and in vivo . Cell Death Dis.2 , e117 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Parmigiani RB , XuWS , Venta-PerezGet al. HDAC6 is a specific deacetylase of peroxiredoxins and is involved in redox regulation . Proc. Natl Acad. Sci. USA105 ( 28 ), 9633 – 9638 ( 2008 ).
   PubMed Web of Science ®Google Scholar
• Gao L , CuetoMA , AsselbergsF , AtadjaP . Cloning and functional characterization of HDAC11: a novel member of the human histone deacetylase family . J. Biol. Chem.277 ( 28 ), 25748 – 25755 ( 2002 ).
   PubMed Web of Science ®Google Scholar
• Girdwood D , BumpassD , VaughanOAet al. P300 transcriptional repression is mediated by SUMO modification . Mol. Cell11 ( 4 ), 1043 – 1054 ( 2003 ).
   PubMed Web of Science ®Google Scholar
• Westendorf JJ , ZaidiSK , CascinoJEet al. Runx2 (Cbfa1, AML-3) interacts with histone deacetylase 6 and represses the p21(CIP1/WAF1) promoter . Mol. Cell Biol.22 ( 22 ), 7982 – 7992 ( 2002 ).
   PubMed Web of Science ®Google Scholar
• Palijan A , FernandesI , BastienYet al. Function of histone deacetylase 6 as a cofactor of nuclear receptor coregulator LCoR . J. Biol. Chem.284 ( 44 ), 30264 – 30274 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Karius T , SchnekenburgerM , DicatoM , DiederichM . MicroRNAs in cancer management and their modulation by dietary agents . Biochem. Pharmacol.83 ( 12 ), 1591 – 1601 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Schnekenburger M , DiederichM . Epigenetics offer new horizons for colorectal cancer prevention . Curr. Colorectal Cancer Rep.8 ( 1 ), 66 – 81 ( 2012 ).
   PubMedGoogle Scholar
• Seidel C , FloreanC , SchnekenburgerM , DicatoM , DiederichM . Chromatin-modifying agents in anti-cancer therapy . Biochimie94 ( 11 ), 2264 – 2279 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Schnekenburger M , DicatoM , DiederichM . Plant-derived epigenetic modulators for cancer treatment and prevention . Biotechnol. Adv.32 ( 6 ), 1123 – 1132 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Bazzaro M , LinZ , SantillanAet al. Ubiquitin proteasome system stress underlies synergistic killing of ovarian cancer cells by bortezomib and a novel HDAC6 inhibitor . Clin. Cancer Res.14 ( 22 ), 7340 – 7347 ( 2008 ).
   PubMed Web of Science ®Google Scholar
• Bradbury CA , KhanimFL , HaydenRet al. Histone deacetylases in acute myeloid leukaemia show a distinctive pattern of expression that changes selectively in response to deacetylase inhibitors . Leukemia19 ( 10 ), 1751 – 1759 ( 2005 ).
   PubMed Web of Science ®Google Scholar
• Kanno K , KannoS , NittaHet al. Overexpression of histone deacetylase 6 contributes to accelerated migration and invasion activity of hepatocellular carcinoma cells . Oncol. Rep.28 ( 3 ), 867 – 873 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Jung KH , NohJH , KimJKet al. Histone deacetylase 6 functions as a tumor suppressor by activating c-Jun NH2-terminal kinase-mediated beclin 1-dependent autophagic cell death in liver cancer . Hepatology56 ( 2 ), 644 – 657 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Marquard L , GjerdrumLM , ChristensenIJ , JensenPB , SehestedM , RalfkiaerE . Prognostic significance of the therapeutic targets histone deacetylase 1, 2, 6 and acetylated histone H4 in cutaneous T-cell lymphoma . Histopathology53 ( 3 ), 267 – 277 ( 2008 ).
   PubMed Web of Science ®Google Scholar
• Van Damme M , CrompotE , MeulemanNet al. HDAC isoenzyme expression is deregulated in chronic lymphocytic leukemia B-cells and has a complex prognostic significance . Epigenetics7 ( 12 ), 1403 – 1412 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Zhang Z , YamashitaH , ToyamaTet al. HDAC6 expression is correlated with better survival in breast cancer . Clin. Cancer Res.10 ( 20 ), 6962 – 6968 ( 2004 ).
   PubMed Web of Science ®Google Scholar
• Yoshida N , OmotoY , InoueAet al. Prediction of prognosis of estrogen receptor-positive breast cancer with combination of selected estrogen-regulated genes . Cancer Sci.95 ( 6 ), 496 – 502 ( 2004 ).
   PubMed Web of Science ®Google Scholar
• Park SY , JunJA , JeongKJet al. Histone deacetylases 1, 6 and 8 are critical for invasion in breast cancer . Oncol. Rep.25 ( 6 ), 1677 – 1681 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Pandey UB , NieZ , BatleviYet al. HDAC6 rescues neurodegeneration and provides an essential link between autophagy and the UPS . Nature447 ( 7146 ), 859 – 863 ( 2007 ).
   PubMed Web of Science ®Google Scholar
• Simoes-Pires C , ZwickV , NurissoA , SchenkerE , CarruptPA , CuendetM . HDAC6 as a target for neurodegenerative diseases: what makes it different from the other HDACs?Mol. Neurodegener.8 , 7 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Chapel HM , EsiriMM , WilcockGK . Immunoglobulin and other proteins in the cerebrospinal fluid of patients with Alzheimer’s disease . J. Clin. Pathol.37 ( 6 ), 697 – 699 ( 1984 ).
   PubMed Web of Science ®Google Scholar
• Glenner GG , WongCW . Alzheimer’s disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein . Biochem. Biophys. Res. Commun.120 ( 3 ), 885 – 890 ( 1984 ).
   PubMed Web of Science ®Google Scholar
• Kim C , ChoiH , JungESet al. HDAC6 inhibitor blocks amyloid beta-induced impairment of mitochondrial transport in hippocampal neurons . PLoS ONE7 ( 8 ), e42983 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Selenica ML , BennerL , HousleySBet al. Histone deacetylase 6 inhibition improves memory and reduces total tau levels in a mouse model of tau deposition . Alzheimers Res. Ther.6 ( 1 ), 12 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Spillantini MG , SchmidtML , LeeVM , TrojanowskiJQ , JakesR , GoedertM . Alpha-synuclein in Lewy bodies . Nature388 ( 6645 ), 839 – 840 ( 1997 ).
   PubMed Web of Science ®Google Scholar
• Du G , LiuX , ChenXet al. Drosophila histone deacetylase 6 protects dopaminergic neurons against {alpha}-synuclein toxicity by promoting inclusion formation . Mol. Biol. Cell21 ( 13 ), 2128 – 2137 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• Iwata A , RileyBE , JohnstonJA , KopitoRR . HDAC6 and microtubules are required for autophagic degradation of aggregated huntingtin . J. Biol. Chem.280 ( 48 ), 40282 – 40292 ( 2005 ).
   PubMed Web of Science ®Google Scholar
• Dompierre JP , GodinJD , CharrinBCet al. Histone deacetylase 6 inhibition compensates for the transport deficit in Huntington’s disease by increasing tubulin acetylation . J. Neurosci.27 ( 13 ), 3571 – 3583 ( 2007 ).
   PubMed Web of Science ®Google Scholar
• Bobrowska A , PaganettiP , MatthiasP , BatesGP . Hdac6 knock-out increases tubulin acetylation but does not modify disease progression in the R6/2 mouse model of Huntington’s disease . PLoS ONE6 ( 6 ), e20696 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Sakaguchi S , SakaguchiN , AsanoM , ItohM , TodaM . Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25): breakdown of a single mechanism of self-tolerance causes various autoimmune diseases . J. Immunol.155 ( 3 ), 1151 – 1164 ( 1995 ).
   PubMed Web of Science ®Google Scholar
• Hori S , NomuraT , SakaguchiS . Control of regulatory T cell development by the transcription factor Foxp3 . Science299 ( 5609 ), 1057 – 1061 ( 2003 ).
   PubMed Web of Science ®Google Scholar
• De Zoeten EF , WangL , ButlerKet al. Histone deacetylase 6 and heat shock protein 90 control the functions of Foxp3(+) T-regulatory cells . Mol. Cell. Biol.31 ( 10 ), 2066 – 2078 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Beier UH , WangL , HanR , AkimovaT , LiuY , HancockWW . Histone deacetylases 6 and 9 and sirtuin-1 control Foxp3+ regulatory T cell function through shared and isoform-specific mechanisms . Sci. Signal5 ( 229 ), ra45 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Kalin JH , ButlerKV , AkimovaT , HancockWW , KozikowskiAP . Second-generation histone deacetylase 6 inhibitors enhance the immunosuppressive effects of Foxp3+ T-regulatory cells . J. Med. Chem.55 ( 2 ), 639 – 651 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Pan F , FanH , LiuZ , JiangS . T cell signaling targets for enhancing regulatory or effector function . Sci. Signal5 ( 235 ), pe32 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Hsieh IN , LiouJP , LeeHY , LaiMJ , LiYH , YangCR . Preclinical anti-arthritic study and pharmacokinetic properties of a potent histone deacetylase inhibitor MPT0G009 . Cell Death Dis.5 , e1166 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Ahmed S , RiegseckerS , BeamerMet al. Largazole, a class I histone deacetylase inhibitor, enhances TNF-alpha-induced ICAM-1 and VCAM-1 expression in rheumatoid arthritis synovial fibroblasts . Toxicol. Appl. Pharmacol.270 ( 2 ), 87 – 96 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Vishwakarma S , IyerLR , MuleyMet al. Tubastatin, a selective histone deacetylase 6 inhibitor shows anti-inflammatory and anti-rheumatic effects . Int. Immunopharmacol.16 ( 1 ), 72 – 78 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Bedinger P , MoriartyA , Von BorstelRC , 2nd , DonovanNJ , SteimerKS , LittmanDR . Internalization of the human immunodeficiency virus does not require the cytoplasmic domain of CD4 . Nature334 ( 6178 ), 162 – 165 ( 1988 ).
   PubMed Web of Science ®Google Scholar
• Valenzuela-Fernandez A , AlvarezS , Gordon-AlonsoMet al. Histone deacetylase 6 regulates human immunodeficiency virus type 1 infection . Mol. Biol. Cell16 ( 11 ), 5445 – 5454 ( 2005 ).
   PubMed Web of Science ®Google Scholar
• Carroll R , PeterlinBM , DerseD . Inhibition of human immunodeficiency virus type 1 Tat activity by coexpression of heterologous trans activators . J. Virol.66 ( 4 ), 2000 – 2007 ( 1992 ).
   PubMed Web of Science ®Google Scholar
• Wei P , GarberME , FangSM , FischerWH , JonesKA . A novel CDK9-associated C-type cyclin interacts directly with HIV-1 Tat and mediates its high-affinity, loop-specific binding to TAR RNA . Cell92 ( 4 ), 451 – 462 ( 1998 ).
   PubMed Web of Science ®Google Scholar
• Huo L , LiD , SunXet al. Regulation of Tat acetylation and transactivation activity by the microtubule-associated deacetylase HDAC6 . J. Biol. Chem.286 ( 11 ), 9280 – 9286 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Rosenthal AS , ShevachEM . Function of macrophages in antigen recognition by guinea pig T lymphocytes. I. Requirement for histocompatible macrophages and lymphocytes . J. Exp. Med.138 ( 5 ), 1194 – 1212 ( 1973 ).
   PubMed Web of Science ®Google Scholar
• Cheng F , LienlafM , Perez-VillarroelPet al. Divergent roles of histone deacetylase 6 (HDAC6) and histone deacetylase 11 (HDAC11) on the transcriptional regulation of IL10 in antigen presenting cells . Mol. Immunol.60 ( 1 ), 44 – 53 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Serrador JM , CabreroJR , SanchoD , MittelbrunnM , UrzainquiA , Sanchez-MadridF . HDAC6 deacetylase activity links the tubulin cytoskeleton with immune synapse organization . Immunity20 ( 4 ), 417 – 428 ( 2004 ).
   PubMed Web of Science ®Google Scholar
• Kwon S , ZhangY , MatthiasP . The deacetylase HDAC6 is a novel critical component of stress granules involved in the stress response . Genes Dev.21 ( 24 ), 3381 – 3394 ( 2007 ).
   PubMed Web of Science ®Google Scholar
• Legros S , BoxusM , GatotJSet al. The HTLV-1 Tax protein inhibits formation of stress granules by interacting with histone deacetylase 6 . Oncogene30 ( 38 ), 4050 – 4062 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Fujita T , KimuraY , MiyamotoM , BarsoumianEL , TaniguchiT . Induction of endogenous IFN-alpha and IFN-beta genes by a regulatory transcription factor, IRF-1 . Nature337 ( 6204 ), 270 – 272 ( 1989 ).
   PubMed Web of Science ®Google Scholar
• Chattopadhyay S , FensterlV , ZhangY , VeleeparambilM , WetzelJL , SenGC . Inhibition of viral pathogenesis and promotion of the septic shock response to bacterial infection by IRF-3 are regulated by the acetylation and phosphorylation of its coactivators . mBio4 ( 2 ), ( 2013 ).
   Web of Science ®Google Scholar
• Husain M , HarrodKS . Enhanced acetylation of alpha-tubulin in influenza A virus infected epithelial cells . FEBS Lett.585 ( 1 ), 128 – 132 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Butler KV , KalinJ , BrochierC , VistoliG , LangleyB , KozikowskiAP . Rational design and simple chemistry yield a superior, neuroprotective HDAC6 inhibitor, tubastatin A . J. Am. Chem. Soc.132 ( 31 ), 10842 – 10846 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• Bergman JA , WoanK , Perez-VillarroelP , VillagraA , SotomayorEM , KozikowskiAP . Selective histone deacetylase 6 inhibitors bearing substituted urea linkers inhibit melanoma cell growth . J. Med. Chem.55 ( 22 ), 9891 – 9899 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Hackanson B , RimmeleL , BenkisserMet al. HDAC6 as a target for antileukemic drugs in acute myeloid leukemia . Leuk. Res.36 ( 8 ), 1055 – 1062 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Jochems J , BouldenJ , LeeBGet al. Antidepressant-like properties of novel HDAC6-selective inhibitors with improved brain bioavailability . Neuropsychopharmacology39 ( 2 ), 389 – 400 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Lee JH , MahendranA , YaoYet al. Development of a histone deacetylase 6 inhibitor and its biological effects . Proc. Natl Acad. Sci. USA110 ( 39 ), 15704 – 15709 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Schafer S , SaundersL , EliseevaEet al. Phenylalanine-containing hydroxamic acids as selective inhibitors of class IIb histone deacetylases (HDACs) . Bioorg. Med. Chem.16 ( 4 ), 2011 – 2033 ( 2008 ).
   PubMed Web of Science ®Google Scholar
• Haggarty SJ , KoellerKM , WongJC , GrozingerCM , SchreiberSL . Domain-selective small-molecule inhibitor of histone deacetylase 6 (HDAC6)-mediated tubulin deacetylation . Proc. Natl Acad. Sci. USA100 ( 8 ), 4389 – 4394 ( 2003 ).
   PubMed Web of Science ®Google Scholar
• Hideshima T , BradnerJE , WongJet al. Small-molecule inhibition of proteasome and aggresome function induces synergistic antitumor activity in multiple myeloma . Proc. Natl Acad. Sci. USA102 ( 24 ), 8567 – 8572 ( 2005 ).
   PubMed Web of Science ®Google Scholar
• Namdar M , PerezG , NgoL , MarksPA . Selective inhibition of histone deacetylase 6 (HDAC6) induces DNA damage and sensitizes transformed cells to anticancer agents . Proc. Natl Acad. Sci. USA107 ( 46 ), 20003 – 20008 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• Mithraprabhu S , KhongT , JonesSS , SpencerA . Histone deacetylase (HDAC) inhibitors as single agents induce multiple myeloma cell death principally through the inhibition of class I HDAC . Br. J. Haematol.162 ( 4 ), 559 – 562 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Santo L , HideshimaT , KungALet al. Preclinical activity, pharmacodynamic, and pharmacokinetic properties of a selective HDAC6 inhibitor, ACY-1215, in combination with bortezomib in multiple myeloma . Blood119 ( 11 ), 2579 – 2589 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Witt O , DeubzerHE , MildeT , OehmeI . HDAC family: what are the cancer relevant targets?Cancer Lett.277 ( 1 ), 8 – 21 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Rosik L , NiegischG , FischerU , JungM , SchulzWA , HoffmannMJ . Limited efficacy of specific HDAC6 inhibition in urothelial cancer cells . Cancer Biol. Ther.15 ( 6 ), 742 – 757 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Kalin JH , BergmanJA . Development and therapeutic implications of selective histone deacetylase 6 inhibitors . J. Med. Chem.56 ( 16 ), 6297 – 6313 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Smil DV , MankuS , ChantignyYAet al. Novel HDAC6 isoform selective chiral small molecule histone deacetylase inhibitors . Bioorg. Med. Chem. Lett.19 ( 3 ), 688 – 692 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Blackburn C , BarrettC , ChinJet al. Potent histone deacetylase inhibitors derived from 4-(aminomethyl)-N-hydroxybenzamide with high selectivity for the HDAC6 isoform . J. Med. Chem.56 ( 18 ), 7201 – 7211 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Chen Y , Lopez-SanchezM , SavoyDN , BilladeauDD , DowGS , KozikowskiAP . A series of potent and selective, triazolylphenyl-based histone deacetylases inhibitors with activity against pancreatic cancer cells and Plasmodium falciparum . J. Med. Chem.51 ( 12 ), 3437 – 3448 ( 2008 ).
   PubMed Web of Science ®Google Scholar
• Kozikowski AP , TapadarS , LuchiniDN , KimKH , BilladeauDD . Use of the nitrile oxide cycloaddition (NOC) reaction for molecular probe generation: a new class of enzyme selective histone deacetylase inhibitors (HDACIs) showing picomolar activity at HDAC6 . J. Med. Chem.51 ( 15 ), 4370 – 4373 ( 2008 ).
   PubMed Web of Science ®Google Scholar
• Inks ES , JoseyBJ , JesinkeySR , ChouCJ . A novel class of small molecule inhibitors of HDAC6 . ACS Chem. Biol.7 ( 2 ), 331 – 339 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Yu CW , ChangPT , HsinLW , ChernJW . Quinazolin-4-one derivatives as selective histone deacetylase-6 inhibitors for the treatment of Alzheimer’s disease . J. Med. Chem.56 ( 17 ), 6775 – 6791 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Zuco V , De CesareM , CincinelliRet al. Synergistic antitumor effects of novel HDAC inhibitors and paclitaxel in vitro and in vivo . PLoS ONE6 ( 12 ), e29085 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Clinical Trial Database . www.clinicaltrials.gov .
   Google Scholar
• Acetylon Pharmaceuticals Inc . www.acetylon.com .
   Google Scholar