Advanced search
Publication Cover
Expert Opinion on Emerging Drugs Volume 9, 2004 - Issue 1
Submit an article Journal homepage
174
Views
69
CrossRef citations to date
0
Altmetric
Review

Histone modification enzymes: novel targets for cancer drugs

Rebecca Kristeleit Institute of Cancer Research, 15 Cotswold Rd, Sutton, Surrey, SM2 5NG, UK. [email protected]
,
Lindsay Stimson Institute of Cancer Research, 15 Cotswold Rd, Sutton, Surrey, SM2 5NG, UK. [email protected]
,
Paul Workman Institute of Cancer Research, 15 Cotswold Rd, Sutton, Surrey, SM2 5NG, UK. [email protected]
&
Wynne Aherne Institute of Cancer Research, 15 Cotswold Rd, Sutton, Surrey, SM2 5NG, UK. [email protected]
Pages 135-154 | Published online: 02 Mar 2005

Bibliography

  • BALL P: Portrait of a molecule. Nature (2003) 421(6920:421–422.
  • FELSENFIELD G, GROUDINE M: Controlling the double helix. Nature (2003) 421(6921)448–453.
  • •Provides interesting discussion of epigenetic mechanisms.
  • KORNBERG RD: Chromatin structure: a repeating unit of histones and DNA. Science (1974) 184:868–871.
  • ••Landmark paper describing chromatinstructure.
  • WEINTRAUB H, GROUDINE M: Chromosomal subunits in active genes have an altered conformation. Science (1976) 193:848–856.
  • LUGER K, MADER AW, RICHMOND RK, SARGENT DF, RICHMOND TJ: Crystal structure of the nucleosome core particle at 2.8A resolution. Nature (1997) 389:251–260.
  • ••First report of the crystal structure of thenucleosome.
  • CHEUNG P, ALLIS CD, SASS ONE-CORSIP: Signalling to chromatin through histone modifications. Cell (2000) 103:263–271.
  • MARMORSTEIN R: Protein modules that manipulate histone tails for chromatin regulation. Nat. Rev Mol. Cell Biol(2001) 2:422–432.
  • •Useful review of histone-protein Interactions regulating chromatin.
  • STRAHL BD, ALLIS CD: The language of covalent histone modifications. Nature (2000) 403:41–45.
  • ••The first paper to suggest an interactivelanguage between various histone modifications termed the 'histone code'.
  • TURNER BM: Cellular memory and the histone code. Cell (2002) 111:285–291.
  • ••Further definition of the histone code.
  • BROWN R, STRATHDEE G: Epigenomics and epigenetic therapy of cancer. Trends Mol Med. (2002) 11:15–21.
  • CRESS WD, SETO E: Histone deacetylases, transcriptional control and cancer.j Cell Phys. (2000) 184:1–16.
  • •A thorough, early review of the association between histone deacetylation and cancer.
  • MAHLKNECHT U, HOELZER D: Histone acetylation modifiers in the pathogenesis of malignant disease. Mol Med. (2000) 6:623–644.
  • TIMMERMANN S, LEHRMANN H, POLESSKAYA A, HAREL-BELLAN A: Histone acetylation and disease. Cell Mol Life Sci. (2001) 58:728–736.
  • MARKS PA, RICHON VM, BRESLOW R, RIFKIND RA: Histone deacetylase inhibitors as new anti-cancer drugs. Curl: Opin. Oncol (2001) 13:477–483.
  • DAVIS PK, BRACKMANN RK: Chromatin remodelling and cancer. Cancer Bid. Ther. (2003) 2:22–29.
  • •Review focusing on the relationship between cancer and regulation of chromatin structure.
  • RICE JC, ALLIS CD: Histone methylation versus histone acetylation: new insights into epigenetic regulation. Curl: Opin. Cell Biol. (2001) 13:263–273.
  • ••In-depth discussion of the interactionbetween histone acetylation and methylation.
  • BANNISTER AJ, SCHNEIDER R, KOUZARIDES T: Histone methylation: dynamic or static? Cell (2002) 109:801–806.
  • ••Discussion of the role of histonemethylation in chromatin regulation and gene expression.
  • BEISEL C, IMHOF A, GREEN J, KREMMER E, SAUER F: Histone methylation by the Drosophila epigenetic transcriptional regulator Ash 1. Nature (2002) 419(6909):857–862.
  • HANS F, DIMITROV S: Histone H3 phosphorylation and cell division. Oncogene (2001) 20:3021–3027.
  • GOTO H, YASUI Y, NIGG EA, INAGAKI M: Aurora-B phosphorylates Histone H3 at serine 28 with regard to the mitotic chromosome condensation. Genes Cells (2002) 7:11–17.
  • RAMASWAMY V, WILLIAMS JS, ROBINSON KM, SOPKO RL, SCHULTZ MC: Global control of histone modification by the anaphase-promoting complex. Mol Cell Bid. (2003) 24:9136–9149.
  • MURNION ME, ADAMS RR, CALLISTER DM, ALLIS CD, EARNSHAW WC, SWEDLOW JR: Chromatin-associated protein phosphatase 1 regulates Aurora B and histone H3 phosphorylation. J. Biol. Chem. (2001) 276:26656–26665.
  • ALLFREY VG, FAULKNER R, MIRSKY AE: Acetylation and methylation of histones and their possible role in the regulation of RNA synthesis. Proc. Natl. Acad. Sci. USA (1964) 51:786–794.
  • GRUNSTEIN M: Histone acetylation in chromatin structure and transcription. Nature (1997) 389:349–352.
  • ••Excellent early review outlining theImportant effects of histone acetylation on gene expression.
  • STRUHL K: Histone acetylation and transcriptional regulatory mechanisms. Genes Dev. (1998) 12:599–606.
  • CAMERON EE, BACHMAN KE, MYOHANEN S, HERMAN JG, BAYLIN SB: Synergy of demethylation and histone deacetylase inhibition in the re-expression of genes silenced in cancer. Nat. Genet. (1999) 21:103–107.
  • •Description of the important synergistic interaction between methylation and acetylation.
  • KOUZARIDES T: Acetylation: a regulatory modification to rival phophorylation? EMBO J. (2000) 19:1176–1179.
  • GREGORY PD, WAGNER K, HORZ W: Histone acetylation and chromatin remodelling. Exp. Cell Res. (2001) 265:195–202.
  • MORALES V, RICHARD-FOY H: Role of histone N-terminal tails and their acetylation in nucleosome dynamics. Mol Cell Bid. (2000) 20:7230–7237.
  • WOLFFE AP, HAYES JJ: Chromatin disruption and modification. Nucleic Adds Res. (1999) 27:711–720.
  • STERNER DE, BERGER SL: Acetylation of histones and transcription-related factors. Microbial. Mol Biol. Rev (2000) 64:435–459.
  • DE RUIJTER AJ, VAN GENNIP AH, CARON HN, KEMP S, VAN KUILENBURG AB: Histone deacetylases: characterisation of the classical HDAC family. Biochem. 1 (2003) 370:737–749.
  • ••A concise and thorough review outliningthe known effects of individual HDAC enzymes.
  • GROZINGER CM, SCHREIBER SL: Deacetylase enzymes: biological functions and the use of small molecule inhibitors. Chem. Biol. (2002) 9:3–16.
  • ••Review covering both HDAC enzymebiology and HDACI effects.
  • ZHANG Y, LI N, CARON C et al: HDAC-6 interacts with and deacetylates tubulin and microtubules in vivo. EMBO (2003) 22:1168–79.
  • •One of the first reports describing substrate specificity for an HDAC enzyme.
  • LIU Y, COLOSIMO AL, YANG X-J, LIAO D: Adenovirus ElB 55-kilodalton oncoprotein inhibits p53 acetylation by PCAE Ma. Cell. Biol. (2000) 20:5540–5553.
  • GU W, ROEDER RG: Activation of p53 sequence-specific DNA binding by acetylation of the p53 C-terminal domain. Cell (1997) 90:595–606.
  • KUO MH, ALLIS CD: Roles of histone acetyltransferases and deacetylases in gene regulation. BioEssays (1998) 20:615–626.
  • MARTINEZ-BALBAS MA, BAUER UM, NEILSEN SJ, BREHM A, KOUZARIDES T: Regulation of E2F1 activity by acetylation. EMBO J. (2000) 19:662–671.
  • BOYES J, BYFIELD P, NAKATANI Y, OGRYZKO V: Regulation of activity of the transcription factor GATA-1 by acetylation. Nature (1998) 396:594–598.
  • DHALLUIN C, CARLSON JE, ZENG L, HE C, AGGARWAL AK, ZHOU MM: Structure and ligand of a histone acetyltransferase bromodomain. Nature (1999) 399:491–496.
  • •Demonstration of the HAT bromodomain structure.
  • WORKMAN P: Scoring a bull's-eye against cancer genome targets. Curr. Opin. Pharmacol (2001) 1:342–352.
  • OGRYZKO VV: Mammalian histone acetyltransferases and their complexes. Cell Mol Life Sci. (2001) 58:683–692.
  • NG HH, BIRD A: Histone deacetylases: silencers for hire. Trends Biochem. Sci. (2000) 25:121–126.
  • BERTOS NR, WANG AH, YANG XJ: Class II histone deacetylases: structure, function and regulation. Biochem. Cell Biol. (2001) 79:243–252.
  • FISCHLE W, EMILIANI S, HENDZEL MJ et al.: A new family of human histone deacetylases related to Saccharomyces cerevisiae HDAlp. J. Biol. Chem. (1999) 274:11713–11720.
  • FISCHLE W, KIERMER V, DEQUIEDT F, VERDIN E: The emerging role of class II histone deacetylases. Biochem. Cell Biol. (2001) 79:337–348.
  • IMAI S, ARMSTRONG CM, KAEBERLEIN M, GUARENTE L: Transcriptional silencing and longevity protein Sir2 is a NAD dependent histone deacetylase. Nature (2000) 403:795–800.
  • DUTNALL RN, PILLUS L: DecipheringNAD-dependent deacetylases. Cell (2001) 105:161–164.
  • PARSONS XH, GARCIA SM, PILLUS L, KADONAGA JT: Histone deacetylation by Sir2 generates a transcriptionally repressed nucleoprotein complex. Proc. Natl. Acad. Sci. USA (2003) 100:1609–1614.
  • FINNIN MS, DONIGIAN JR, COHEN A et al.: Structures of a histone deacetylase homologue bound to the TSA and SAHA inhibitors. Nature (1999) 401:188–193.
  • ••Landmark paper illustrating the molecularbinding between HDACI an HDAC enzyme homologues.
  • HUBBERT C, GUARDIOLA A, SHAO R et al: HDAC6 is a microtubule-associated deacetylase. Nature (2002) 417:455–458.
  • ••First evidence for HDAC6 substratespecificity.
  • ALLAND L, MUHLE R, HOU H Jr et al: Role for NCoR and HDAC in Sin3-mediated transcriptional repression. Nature (1997) 387(6628):49–55.
  • HEINZEL T, LAVINSKY RM, MULLEN TM et al: A complex containing NCoR, mSin3 and histone deacetylase mediates transcriptional repression. Nature (1997) 387:43–48.
  • YAO YL, YANG WM, SETO E: Regulation of transcription factor YY1 by acetylation and deacetylation. Ma. Cell. Biol. (2001) 21:5979–5991.
  • BLACK AR, BLACK JD, AZIZKHAN-CLIFFORD J: Spl and Kruppel-like factor family of transcription factors in cell growth regulation and cancer. J. Cell Physiol (2001) 188:143–160.
  • MAGNAGHI-JAULIN L, GROISMAN R, NAGUIBNEVA I et al: Retinoblastoma protein represses transcription by recruiting a histone deacetylase. Nature (1998) 391:601–605.
  • •Discovery of the link between Rb and HDAC enzymes.
  • CHEN D, MA H, HONG H et al.: Regulation of transcription by a protein methyltransferase. Science (1999) 284:2174–2177.
  • STRAHL BD, OHBA R, COOK RG, ALLIS CD: Methylation of histone H3 at lysine 4 is highly conserved and correlates with transcriptionally active nuclei in 7etrahymena. Proc. Natl. Acad. Sci. USA (1999) 96:14967–14972.
  • •Evidence for the role of histone methylation in transcriptional activation.
  • JENUWEIN T, ALLIS CD: Translating the histone code. Science (2001) 293:1074–1080.
  • SANTOS-ROSA H, SCHNEIDER R, BANNISTER AJ et al.: Active genes are tri-methylated at K4 of histone H3. Nature (2002) 419:407–411.
  • SCHNEIDER R, BANNISTER AJ, KOUZARIDES T: Unsafe SETs: histone lysine methyltransferases and cancer. Trends Biochem. Sci (2002) 27:396–402.
  • •Review of histone methyltransferase enzymes and discussion of their possible role in cancer.
  • FENG Q, WANG H, NG GH et al: Methylation of H3-lysine9 is mediated by a new family of HMTases without a SET domain. Curr. Biol. (2002) 12:1052–1058.
  • KOUZARIDES T: Histone methylation in transcriptional control. Curr. Opin. Genet. Dev. (2002) 9:40–48.
  • BREILING A, ORLANDO V: SET domain proteins reset gene expression. Nat. Struct. Biol. (2002) 9:894–896.
  • REA S, EISENHABER F, O'CARROLL D et al.: Regulation of chromatin structure by site-specific histone H3 methyltransferases. Nature (2000) 406:593–599.
  • •This review focuses on the mechanisms by which methyltransferase enzymes regulate chromatin.
  • XIAO B, JING C, WILSON JR et al: Structure and catalytic mechanism of the human histone methyltranferase SET7/9. Nature (2003) 421(6923):652–656.
  • •Discovery of the structure of a human histone methyltransferase.
  • ZHANG Y, REINBERG D: Transcription regulation by histone methylation: interplay between different covalent modifications of the core histone tails. Genes Dev. (2001) 15:2343–2360.
  • WANG H, HUANG ZQ, XIA L et al: Methylation of histone H4 at arginine 3 facilitates transcriptional activation by nuclear hormone receptor. Science (2001) 293(5530:853–857.
  • CHEN D, HUANG SM, STALLCUP MR: Synergistic p160 coactivator dependent enhancement of estrogen receptor function by CARM1 and p300. I Biol. Chem. (2000) 275:40810–40816.
  • WET Y, MIZZEN CA, COOK RG, GOROVSKY MA, ALLIS CD: Phosphorylation of histone H3 at serine 10 is correlated with chromosome condensation during mitosis and meiosis in 7etrahymena. Proc. Nati Acad. Sci. USA (1998) 95:7480–7484.
  • KATAYAMA H, BRINKLEY WR, SEN S: The Aurora kinases: role in cell transformation and tumorigenesis. Cancer Metastasis Rev (2003) 22:451–464.
  • ••Review and discussion of the biology ofAurora kinases.
  • BISCHOFF JR, ANDERSON L, ZHU Y et al.: A homologue of Drosophila Aurora kinase is oncogenic and amplified in human colorectal cancers. EMBO J. (1998) 17:3052–3065.
  • CARMENA M, EARNSHAW WC: The cellular geography of Aurora kinases. Nat. Rev Mol. Cell Biol. (2003) 4:842–854.
  • ••Review and discussion of the biology ofAurora kinases.
  • MOORE SC: The elusive structural role of ubiquitinated histones. Biochem. Cell Biol. (2002) 80:311–319.
  • SUN Z-W, ALLIS CD: Ubiquitination of histone H2B regulates H3 methylation and gene silencing in yeast. Nature (2002) 418:104–108.
  • ••Good description of the effects of histoneubiquitination.
  • BRIGGS SD, XIAO T, SUN ZW et al: Trans-histone regulatory pathway in chromatin. Nature (2002) 418:498.
  • LADURNER AG: Inactivating chromosomes: a macro domain that minimizes transcription. Mol. (2003) 12:1–3.
  • WADE PA: Transcriptional control at regulatory checkpoints by histone deacetylases: molecular connections between cancer and chromatin. Hum. Mol. Genet. (2001) 10:693–698.
  • •Detailed discussion of the aberrant molecular events linking HDAC activity with cancer.
  • JOHNSTONE R: Histone deacetylase inhibitors: novel drugs for the treatment of cancer. Nat. Rev Drug Discov. (2002) 1:287–299.
  • ••Excellent review of HDACIs.
  • CAIRNS BR: Emerging roles for chromatinremodelling in cancer biology. Trends Cell Biol. (2001) 11:S15–S21.
  • CHAKRABORTY S, SENYUK V, NUCIFORA G: Genetic lesions and perturbation of chromatin architecture: a road to cell transformation. J. Cell Biochem. (2001) 82:310–325.
  • WARNER SL, BEARSS DJ, HAN H, VON HOFF DD: Targeting Aurora-2 kinase in cancer. Mol. Cancer Ther (2003) 2:589–595.
  • GIORDANO A, AVANTAGGIATI ML: p300 and CBP: partners for life and death. J. Cell Physiol (1999) 181:218–230.
  • GAYTHER SA, BATLEY SJ, LINGER L, BANNISTER A, THORPE K, CHIN SF: Mutations truncating the EP300 acetylase in human cancers. Nat. Genet. (2000) 24:300–303.
  • ••Characterisation of mutations in theHAT, p300.
  • MURAOKA M, KONISHI M, KIKUCHI-YANOSHITA R et al: p300 gene alterations in colorectal and gastric carcinomas. Oncogene (1996) 12:1565–1569.
  • •Genetic alterations of p300 in cancer.
  • GILES RH, PETERS DJ, BREUNING MH: Conjunction dysfunction: CBP/p300 in human disease. Trends Genet. (1998) 14:178–183.
  • PETRIJ F, GILES RH, DAUWERSE HG et al.: Rubenstein-Taybi syndrome caused by mutations in the transcriptional co-activator CBP. Nature (1995) 376:348–351.
  • KUNG AL, REBEL VI, BRONSON RT et al.: Gene dose-dependent control of haematopoiesis and haematologic tumour suppression by CBP. Genes Dev. (2000) 14:272–277.
  • TANAKA T, NARUSE I, MACKAWA T, MASUYA H, SHIROISHI T, ISHII S: Abnormal skeletal patterning in embryos lacking a single CBPallele: a partial similarity with Rubenstein-Taybi syndrome. Proc. Natl. Acad. Sci. USA (1997) 94:10215–10220.
  • SAKAI K, NAGAHARA H, ABE K, OBATA J: Loss of heterozygosity on chromosome 16 in hepatocellular carcinoma. J. Gastroenterof Hepatol (1992) 7:88–92.
  • LUNDBLAD JR, KWOK RP, LAURANCE ME, HARTER ML, GOODMAN RH: Adenoviral E1A-associated protein p300 as a functional homologue of the transcriptional co-activator CBP. Nature (1995) 374:85–88.
  • ECKNER R, LUDLOW JW, LILL NL et al: Association of p300 and CBP with simian virus 40 large T antigen. Mol. Cell Biol. (1996) 16:3454–3464.
  • ANZICK SL, KONONEN J, WALKER RL et al.: AIB1, a steroid receptor coactivator amplified in breast and ovarian cancer. Science (1997) 277:965–968.
  • BERNS EM, VAN STAVEREN IL, KLIJN JG, FOEKENS JA: Predictive value of SRC-1 for tamoxifen response of recurrent breast cancer. Breast Cancer Res. Treat. (1998) 48:87–92.
  • ROWLEY JD, RESHMI S, SOBULO 0et al.: All patients with the t(11; 16) (q23;p13.3) that involves MLL and CBP have treatment related haematologic disorders. Blood (1997) 90: 535–541.
  • AYTON PM, CLEARY ML: Molecular mechanisms of leukaemogenesis mediated by MLL fusion proteins. Oncogene (2001) 20:5695–5707.
  • IDA K, KITABAYASHI I, TAKI T et al:Adenoviral E1A-associated protein p300 is involved in acute myeloid leukaemia with t(11;22)(q23;q13). Blood (1997) 90:4699–4704.
  • YAO YL, OH SP, FUCHS M et al: Gene dosage-dependent embryonic development and proliferation defects in mice lacking the transcriptional integrator p300. Cell (1998) 93:361-372. •In vivo study of p300knockdown in mice.
  • DEBES JD, SEBO J, LOHSE CM, MURPHY LM, HAUGEN DL, TINDALL DJ: p300 in prostate cancer proliferation and progression. Cancer Res. (2003) 63:7638–7640.
  • •p300 in prostate cancer.
  • MINUCCI S, NERVI C, LO COCO F, PELICCI PG: Histone deacetylases: a common molecular target for differentiation treatment of acute myeloid leukaemias? Oncogene (2001) 20:3110–3115.
  • LIN RJ, NAGY L, INOUE S, SHAO W, MILLER WH Jr, EVANS RM: Role of the histone deacetylase complex in acute promyelocytic leukaemia. Nature (1998) 391:811–814.
  • •Description of aberrant fusion protein activity in APL.
  • HE LZ, GUIDEZ F, TRIBIOLI C et al: Distinct interactions of PML-RAR alpha and PLZF-RAR alpha with co-repressors determine differential responses to RA in APL. Nat. Genet. (1998) 18:126–135.
  • GRIGNANI F, DE MATTEIS S, NERVI C et al.: Fusion proteins of the retinoic acid receptor-alpha recruit histone deacetylase in promyelocytic leukaemia. Nature (1998) 391:815–818.
  • DHORDAIN P, LIN RJ, QUIEF S et al: The LAZ3 (BCL6) oncoprotein recruits a SMRT/mSin3A/histone deacetylase containing complex to mediate transcriptional repression. Nur. Adds Res. (1998) 26:4645–4651.
  • WANG J, HOSHINO T, REDNER RL, KAJIGAYA S, LIU JM: ETO, fusion partner in t(8:21) acute myeloid leukaemia, represses transcription by interaction with the human NcoR/mSin3.HDAC1 complex. Proc. Natl. Acad. Sci. USA (1998) 95:10860–10865.
  • WANG J, SAUNTHARARAJAH Y, REDNER RL, LUI J: Inhibitors of histone deacetylase relieve ETO-mediated repression and induce differentiation of AML1-ETO leukaemia cells. Cancer Res. (1999) 59:2766–2769.
  • SEARS R, OHTANI K, NEVINS JR: Identification of positively and negatively acting elements regulating expression of the E2F2 gene in response to cell growth signals. Mol. Cell Biol. (1997) 17: 5227–5235.
  • MCARTHUR GA, LAHERTY CD, QUEVA C et al: The Mad protein family links transcriptional repression to cell differentiation. Cold Spring Harbour Symp. Quant Biol. (1998) 63:423–433.
  • DANG CV: c-Myc target genes involved in cell growth, apoptosis and metabolism. Mol. Cell. Biol. (1999) 19:1–11.
  • NOMURA T, KHAN MM, KAUL SC et al.: Ski is a component of the histone deacetylase complex required for transcriptional repression by Mad and thyroid hormone receptor. Genes Dev. (1999) 13:412–423.
  • BREHM A, MISKA EA, MCCANCE DJ, REID JL, BANNISTER AJ, KOUZARIDES T: Retinoblastoma protein recruits histone deacetylase to repress transcription. Nature (1998) 391:597–601.
  • SELLERS WR, KAELIN WG Jr: Role of the retinoblastoma protein in the pathogenesis of human cancer. J. Clin Onc. (1997) 15:3301–3312.
  • ZHANG Y, WOODFORD N, XIA X, HAMBURGER AW: Repression of E2F1-mediated transcription by the ErbB3 binding protein Ebp1 involves histone deacetylases. Nur. Acids Res. (2003) 31:2168–2177.
  • KIM MS, KWON HJ, LEE YM et al: Histone deacetylases induce angiogenesis by negative regulation of tumour suppressor genes. Nat. Med. (2001) 7:437–443.
  • ••HDAC effects on angiogenesis.
  • DEROANNE CF, BONJEAN K, SERVOTTE S et al: Histone deacetylase inhibitors as antiangiogenic agents altering vascular endothelial growth factor signalling. Oncogene (2002) 21:427–436.
  • ••HDAC effects on angiogenesis.
  • ROBERTSON KD: DNA methylation, methyltransferases and cancer. Oncogene (2001) 20:3139–3155.
  • ROUNTREE MR, BACHMAN KE, HERMAN JG, BAYLIN SB: DNA methylation, chromatin inheritance and cancer. Oncogene (2001) 20:3156–3165.
  • •Review of DNA methylation including synergism with histone acetylation in cancer.
  • JAENISCH R, BIRD A: Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat. Genet. Suppl. (2003) 33:245–254.
  • PETERS AHFM, O'CARROLL D, SCHERTHAN H et al: Loss of the 5uv39 histone methyltransferases impairs mammalian heterochromatin and genome stability. Cell (2001) 107:323–337.
  • NIELSEN PR, NIETLISPACH D, MOTT HR et al.: Structure of the HP1 chromodomain bound to histone H3 methylated at lysine 9. Nature (2002) 416(6876):103–107.
  • KONDO Y, SHEN L, ISSA JP: Critical role of histone methylation in tumour suppressor gene silencing in colorectal cancer. Mol. Cell. Bid. (2003) 23:206–215.
  • VARAMBALLY S, DHANASEKARAN SM, ZHOU M: The polycomb group protein EZH2 is involved in progression of prostate cancer. Nature (2002) 419:624–629.
  • •Evidence for the role of EZH2 in breast and prostate cancers.
  • KLEER CG, CAO Q, VARAMBALLY S: EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells. Proc. Natl. Acad. Li. USA (2003) 100:11606–11611.
  • •Evidence for the role of EZH2 in breast and prostate cancers.
  • BISCHOFF JR, PLOWMAN GD: The Aurora/IpIlp kinase family: regulators of chromosome segregation and cytokinesis. Trends Cell Bid. (1999) 9:454–459.
  • ZHOU H, KUANG J, ZHONG L et al: Tumour amplified kinase STK/BTAK induces centrosome amplification, aneuploidy and transformation. Nat. Genet. (1998) 20:189–193.
  • MIYOSHI Y, IWAO K, EGAWA C, NOGUCHI S: Association of centrosomal kinase STK15/BTAK mRNA expression with chromosomal instability in human breast cancers. Int. J. Cancer (2001) 92:370–373.
  • ROMANOV SR, KOZAKIEWICZ BK, HOLST CR, STAMPFER MR, HAUPT LM, TISTY TD: Normal human mammary epithelial cells spontaneously escape senescence and acquire genomic changes. Nature (2001) 409:633–637.
  • EWART-TOLAND A, BRIASSOULI P, DE KONIG JP et al: Identification of Stk6/STK15 as a candidate low-penetrance tumour-susceptibility gene in mouse and human. Nat. Genet. (2003) 34:403–412.
  • ANAND S, PENRHYN-LOWE S, VENKITARAMAN AR: Aurora-A amplification overrides the mitotic spindle assembly checkpoint, inducing resistance to Taxol. Cancer Cell (2003) 3:51–62.
  • LAU OD, KUNDU TK, SOCCIO RE et al.: HATs off: Selective synthetic inhibitors of the histone acetyltransferase p300 and PCAE MolCell (1999) 5:589–595.
  • ••First discovery of a HAT inhibitor.
  • CEBRAT M, KIM CM, THOMPSON PR, DAUGHERTY M, COLE PA: Synthesis and analysis of potential prodrugs of coenzyme A analogues for the inhibition of the histone acetyltransferase p300. Bioorg. Med. Chem. (2003) 11:3307–3313.
  • ••First development of a potential prodrugfor HAT inhibition.
  • POUX AN, MARMORSTEIN R: Molecular basis for Gcn5/PCAF histone acetyltransferase selectivity for histone and nonhistone substrates. Biochemistry (2003) 42:14366–14374.
  • TURLAIS F, HARDCASTLE A, ROWLANDS MG et al: High throughput screening (HTS) for identification of histone acetyltransferases using scintillating microplates (FlashPlate Anna]. Biochem. (2001) 298:62–68.
  • STIMSON L, ROWLANDS MG, NEWBATT Y et al: Isothiazolones as novel inhibitors of pcaf and p300 histone acetyltransferase activity. Clin. Cancer Res. (2003) 9(Suppl.):87.
  • BALASUBRAMANYAM K, SWAMINATHAN V, RANGANATHAN A, KUNDU TK: Small molecule modulators of histone acetyltransferase p300. J. Biol. Chem. (2003) 278:19134–19140.
  • CHEETHAM GM, KNEGTEL RM, COLL JT et al.: Crystal structure of Aurora-2, an oncogenic serineithreonine kinase. J. Biol. Chem. (2002) 277:42419–42422.
  • ••Discovery of the structure of Aurora 2.
  • MAHADEVAN D, BEARSS DJ, VANKAYALAPATI H: Structure-based design of novel anti-cancer agents targeting aurora kinases. Curl: Med. Chem. Anti-Canc. Agents (2003) 1:25–34.
  • YOSHIDA M, FURUMAI R, NISHIYAMA M, KOMATSU Y, NISHINO N, HORINOUCHI S: Histone deacetylase as a new target for cancer chemotherapy. Cancer Chemother. Pharmacol (2001) 48\(Suppl. 1):520–526.
  • REMISZEWSKI SW: Recent advances in the discovery of small molecule histone deacetylase inhibitors. Curr. Opin. Drug Discov. Devel. (2002) 5:487–499.
  • ELAUT G, TOROK G, VINKEN M et al: Major Phase I biotransformation pathways of Trichostatin A in rat hepatocytes and in rat and human liver microsomes. Drug Metab. Dispos. (2002) 30:1320–1328.
  • ATADJA P, GAOL, KWON P et al: Selective growth inhibition of tumour cells by a novel histone deacetylase inhibitor, NVP-LAQ824. Cancer Res. (2004) 64:689–695.
  • PLUMB JA, FINN PW, WILLIAMS RJ et al.: Pharmacodynamic response and inhibition of growth of human tumour xenografts by the novel histone deacetylase inhibitor PXD101. Mol. Cancer Ther. (2003) 2:721–728.
  • RICHON VM, SANDHOFF TW, RIFKIND RA, MARKS PA: Histone deacetylase inhibitor selectively induces p21WAF1 expression and gene-associated histone acetylation. Proc. Natl. Acad Sci USA (2000) 97:10014–10019.
  • MARKS PA, RICHON VM, RIFKIND RA: Histone deacetylase inhibitors: inducers of differentiation or apoptosis of transformed cells. J. Nati Cancer Inst. (2000) 92:1210–1216.
  • KELLY WK, RICHON VM, O'CONNOR 0 et al: Phase I clinical trial of histone deacetylase inhibitor: Suberoylanilide hydroxamic acid administered intravenously. Clin. Cancer Res. (2003) 9:3578–3588.
  • KELLY WK, O'CONNOR O, RICHON VM et al: Phase I clinical trial of an oral histone deacetylase inhibitor: Suberoylanilide hydroxamic acid (SAHA). Clin. Cancer Res. (2003) 9(Suppl.):226.
  • ARTS J, VAN EMELEM K, ANGIBAUD P et al.: Small molecule inhibitors of histone deacetylases (HDACs): identification of JNJ16241199, a potent oral antitumour agent. Clin. Cancer Res.. (2003) 9(Suppl.):87.
  • KRUH J: Effects of sodium butyrate, a new pharmacological agent, on cells in culture. Mol. Cell Biochem. (1982) 42:65–82.
  • KIJIMA M, YOSHIDA M, SUGITA K, HORINOUCHI S, BEPPU T: Trapoxin, an antitumour cyclic tetrapeptides an irreversible inhibitor of mammalian histone deacetylase. J. Biol. Chem. (1993) 268:22429–22435.
  • FURUMAI R, KOMATSU Y, NISHINO N, KHOCHBIN S, YOSHIDA M, HORINOUCHI S: Potent histone deacetylase inhibitors built from trichostatin A and cyclic tetrapeptide antibiotics including trapoxin. Proc. Natl. Acad. Sci. USA (2001) 98:87–92.
  • SAITO A, YAMASHITA T, MARIKO Y et al.: A synthetic inhibitor of histone deacetylase, MS-27-275, with marked in vivo antitumour activity against human tumours. Proc. Natl. Acad. Sci. USA (1999) 96:4592–4597.
  • SU GH, SOHN TA, RYU B, KERN SE: A novel histone deacetylase inhibitor identified by high-throughput transcriptional screening of a compound library. Cancer Res. (2000) 60:3137–3142.
  • GROZINGER CM, CHAO ED, BLACKWELL HE, MOAZED D, SCHREIBER SL: Identification of a class of small molecule inhibitors of the sirtuin family of NAD-dependent deacetylases by phenotypic screening. J. Biol. Chem. (2001) 276:38837–38843.
  • GLASER KB, LI J, STAVER MJ, WEI R-Q, ALBERT DH, DAVIDSEN SK: Role of Class I and Class II histone deacetylases in carcinoma cells using siRNA. Biochem. Biophys. Res. Comm. (2003) 310:529–536.
  • HUE, DUL E, SUNG CM et al.: Identification of novel isoform-selective inhibitors within Class I histone deacetylases. Pharmacol. Exp. Ther. (2003) 307:720–728.
  • GLASER KB, STAVER MJ, WARING JF, STENDER J, ULRICH RG, DAVIDSEN SK: Gene expression profiling of mutiple histone deacetylase (HDAC) inhibitors: defining a common gene set produced by HDAC inhibition in T24 and MDA carcinoma cell lines. Mol. Canc. Ther. (2003) 2:151–163.
  • BLAGOSKLONNY MV, ROBEY R, SACKETT DL et al.: Histone deacetylase inhibitors all induce p21 but differentially cause tubulin acetylation, mitotic arrest and cytotoxicity. Mol. Canc. Ther.(2002) 1: 937–941.
  • QIU L, BURGESS A, FAIRLIE DP, LEONARD H, PARSONS PG, GABRIELLI BG: Histone deacetylase inhibitors trigger a G2 checkpoint in normal cells that is defective in tumour cells. Mol. Biol. Cell (2000) 11:2069–2083.
  • SHI H, WEI S, LEU Y-W: Triple analysis of the cancer epigenome: an integrated microarray system for assessing gene expression, DNA methylation and histone acetylation. Cancer Res. (2003) 63:2164–2171.
  • VIGUSHIN DM, COOMBES RC: Histone deacetylase inhibitors in cancer treatment. Anticancer Drugs (2002) 13:1–13.
  • MAGNER WJ, KAZIM AL, STEWART C et al: Activation of MHC Class I, II and CD40 gene expression by histone deacetylase inhibitors. J. Immunol (2000) 165:7017–7024.
  • KWON HJ, KIM MS, KIM MJ, NAKAJIMA H, KIM KW: Histone deacetylase inhibitor FK228 inhibits tumour angiogenesis. Int. J. Cancer (2002) 97:290–296.
  • LIU LT, CHANG HC, CHIANG LC, HUNG WC: Histone deacetylase inhibitor up-regulates RECK to inhibit MMP-2 activation and cancer cell invasion. Cancer Res. (2003) 63:3069–3072.
  • HAN JW, AHN SH, PARK SH et al: Apicidin, a histone deacetylase inhibitor, inhibits proliferation of tumour cells via induction of p21WAF1/Cip 1 and gelsolin. Cancer Res. (2000) 60:6068–6074.
  • FINZER P, KUNTZEN C, SOTO U, ZUR HAUSEN H, ROSL F: Inhibitors of histone deacetylase arrest cell cycle and induce apoptosis in cervical carcinoma cells circumventing human papilloma virus oncogene expression. Oncogene (2001) 20:4768–4776.
  • SANDOR V, SENDEROWICZ A, MERTINS S et al: p21-dependent G1 arrest with downregulation of cyclin D1 with upregulation of cyclin E by the histone deacetylase inhibitor FR901228. BE J. Cancer (2000) 83:817–825.
  • ZHU WG, LAKSHMANAN RR, BEAL MD, OTTERS ON GA: DNA methyltransferase inhibition enhances apoptosis induced by histone deacetylase inhibitors. Cancer Res. (2001) 61:1327–1333.
  • YU X, GUO ZS, MARCU MG et al: Modulation of p53, erbB1, erbB2 and raf-1 expression in lung cancer cells by depsipeptide FR901228. J. Natl. Cancer Inst. (2002) 94:504–513.
  • MALONEY A, WORKMAN P: Hsp90 as a new therapeutic target for cancer therapy: the story unfolds. Expert Opia Biol. Ther. (2002) 2:3–24.
  • CATLEY L, WEISBERG E, TAI Y-T et al: NVP-LAQ824 is a potent novel histone deacetylase inhibitor with significant activity against multiple myeloma. Blood (2003) 102:2615–2622.
  • QIU L, KELSO MJ, HANSEN C, WEST ML, FAIRLIE DP, PARSONS PG: Anti-tumour activity in vitro and in vivo of selective differentiating agents containing hydroxamate. Br. J. Cancer (1999) 80:1252–1258.
  • KIM YB, LEE KH, SUGITA K, YOSHIDA M, HORINOUCHI S: Oxamflatin is a novel antitumour compound that inhibits mammalian histone deacetylase. Oncogene (1999) 18:2461–2470.
  • UEDA H, MANDA T, MATSUMOTO S et al: FR901228, a novel antitumour bicyclic depsipeptide produced by Chromobactedum violaceum No. 968 III. Antitumour activities on experimental tumours in mice. J. Antibiot. (Tokyo) (1994) 47:315–323.
  • GILBERT J, BAKER SD, BOWLING MK et al: A Phase I dose escalation and bioavailability study of oral sodium phenylbutyrate in patients with refractory solid tumor malignancies. Clin. Cancer Res. (2001) 8:2292–2300.
  • CARDUCCI MA, GILBERT J, BOWLING MK et al: A Phase I clinical and pharmacological evaluation of sodium phenylbutyrate on an 120-h infusion schedule. Clin. Cancer Res. (2001) 10:3047–3055.
  • WARRELL RP Jr, HE LZ, RICHON V, CALLEJA E, PANDOLFI PP: Therapeutic targeting of transcription in acute promyelocytic leukaemia by use of an inhibitor of histone deacetylase. J. Natl. Cancer Inst. (1998) 90:1621–1625.
  • PIEKARZ RL, ROBEY R, SANDOR V et al: Inhibitor of histone deacetylation, depsipeptide (FR901228), in the treatment of peripheral and cutaneous T-cell lymphoma: a case report. Blood (2001) 98:2865–2868.
  • SANDOR V, BAKKE S, ROBEY RW et al.: Phase I trial of the histone deacetylase inhibitor, depsipeptide (FR901228, NSC 630176), in patients with refractory neoplasams. Clin. Cancer Res. (2002) 8:718–728.
  • WISINSKI KB: A Phase I study of an oral histone deacetylase inhibitor, MS-275, in patients (pts) with refractory solid tumours and lymphomas. OM. Cancer Res. (2003) 9(Suppl.):92.
  • NIMMANAPALLI R, FUINO L, BALI P et al: Histone deacetylase inhibitor LAQ824 both lowers expression and promotes proteasomal degradation of Bcr-Abl and induces apoptosis of imatinib mesylate-sensitive or refractory chronic myelogenous leukaemia-blast crisis cells. Cancer Res. (2003) 63:5126–5135.
  • AHERNE GW, ROWLANDS MG, STIMSON L, WORKMAN P: Assays for the identification and evaluation of histone acetyltransferase inhibitors. Methods (2002) 26:245–253.
  • SCHMEICHEL KL: Centrosome cycle studies reveal promising candidates for anti-cancer drug design. Breast Cancer Res. (2003) 5:59.
  • BRINKMANN H, DAHLER AL, POPA C et al.: Histone hyperacetylation induced by histone deacetylase inhibitors is not sufficient to cause growth inhibition in human dermal fibroblasts. I Biol. Chem. (2001) 276:22491–22499.
  • HANAHAN D, WEINBERG RA: The hallmarks of cancer. Cell (2000) 100:57–70.
  • WORKMAN P: The opportunities and challenges of personalised genome-based molecular therapies for cancer: targets, technologies and molecular chaperones. Cancer Chemother. Pharmacol. (2003) 52\(Suppl. 1):545–556.

Websites

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Order Reprints Request Corporate Permissions

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

Request Academic Permissions

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.

Related research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.