Home LiteratureArticle Details
PMID: 20553216 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Nonhistone protein acetylation as cancer therapy targets.

Expert review of anticancer therapy ·Vol. 10 ·No. 6 ·2010-06-00 ·Pages 935-54

Singh BN, Zhang G, Hwa YL, Li J, Dowdy SC, Jiang SW

Abstract

Acetylation and deacetylation are counteracting, post-translational modifications that affect a large number of histone and nonhistone proteins. The significance of histone acetylation in the modification of chromatin structure and dynamics, and thereby gene transcription regulation, has been well recognized. A steadily growing number of nonhistone proteins have been identified as acetylation targets and reversible lysine acetylation in these proteins plays an important role(s) in the regulation of mRNA stability, protein localization and degradation, and protein-protein and protein-DNA interactions. The recruitment of histone acetyltransferases (HATs) and histone deacetylases (HDACs) to the transcriptional machinery is a key element in the dynamic regulation of genes controlling cellular proliferation, differentiation and apoptosis. Many nonhistone proteins targeted by acetylation are the products of oncogenes or tumor-suppressor genes and are directly involved in tumorigenesis, tumor progression and metastasis. Aberrant activity of HDACs has been documented in several types of cancers and HDAC inhibitors (HDACi) have been employed for therapeutic purposes. Here we review the published literature in this field and provide updated information on the regulation and function of nonhistone protein acetylation. While concentrating on the molecular mechanism and pathways involved in the addition and removal of the acetyl moiety, therapeutic modalities of HDACi are also discussed.

MeSH Terms
Acetylation Chromosomal Proteins, Non-Histone/metabolism Histone Deacetylase Inhibitors/therapeutic use Humans Neoplasms/drug therapy,enzymology,pathology
Chemicals
Chromosomal Proteins, Non-Histone Histone Deacetylase Inhibitors
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Singh Brahma N
Department of Mycology & Plant Pathology, Institute of Agricultural Sciences, Banaras Hindu University, Varanasi, India.
Zhang Guanghua
Hwa Yi L
Li Jinping
Dowdy Sean C
Jiang Shi-Wen
References (189)
189 references, click to expand
  1. Sirtuins: critical regulators at the crossroads between cancer and aging.
    Oncogene. 2007 Aug 13;26(37):5489-504 PMID: 17694089
  2. Histone deacetylase inhibitors: Potential in cancer therapy.
    J Cell Biochem. 2009 Jul 1;107(4):600-8 PMID: 19459166
  3. Acetylation of non-histone proteins modulates cellular signalling at multiple levels.
    Int J Biochem Cell Biol. 2009 Jan;41(1):185-98 PMID: 18804549
  4. HDAC6 controls major cell response pathways to cytotoxic accumulation of protein aggregates.
    Genes Dev. 2007 Sep 1;21(17):2172-81 PMID: 17785525
  5. Unanticipated repression function linked to erythroid Krüppel-like factor.
    Mol Cell Biol. 2001 May;21(9):3118-25 PMID: 11287616
  6. CREB-binding protein/p300 activates MyoD by acetylation.
    J Biol Chem. 2000 Nov 3;275(44):34359-64 PMID: 10944526
  7. Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer.
    Nat Rev Cancer. 2006 Jan;6(1):38-51 PMID: 16397526
  8. FOXO4 is acetylated upon peroxide stress and deacetylated by the longevity protein hSir2(SIRT1).
    J Biol Chem. 2004 Jul 9;279(28):28873-9 PMID: 15126506
  9. The coregulator exchange in transcriptional functions of nuclear receptors.
    Genes Dev. 2000 Jan 15;14(2):121-41 PMID: 10652267
  10. In vivo destabilization of dynamic microtubules by HDAC6-mediated deacetylation.
    EMBO J. 2002 Dec 16;21(24):6820-31 PMID: 12486003
  11. Reduced expression of class II histone deacetylase genes is associated with poor prognosis in lung cancer patients.
    Int J Cancer. 2004 Oct 20;112(1):26-32 PMID: 15305372
  12. Acetylation of p53 activates transcription through recruitment of coactivators/histone acetyltransferases.
    Mol Cell. 2001 Dec;8(6):1243-54 PMID: 11779500
  13. A phase I study of the oral combination of CI-994, a putative histone deacetylase inhibitor, and capecitabine.
    Ann Oncol. 2004 Nov;15(11):1705-11 PMID: 15520075
  14. Inhibitors of histone deacetylation downregulate the expression of endothelial nitric oxide synthase and compromise endothelial cell function in vasorelaxation and angiogenesis.
    Circ Res. 2002 Nov 1;91(9):837-44 PMID: 12411399
  15. The flavoring agent dihydrocoumarin reverses epigenetic silencing and inhibits sirtuin deacetylases.
    PLoS Genet. 2005 Dec;1(6):e77 PMID: 16362078
  16. Chaperoning steroid hormone signaling via reversible acetylation.
    Nucl Recept Signal. 2005;3:e004 PMID: 16604172
  17. Acetylation-dependent signal transduction for type I interferon receptor.
    Cell. 2007 Oct 5;131(1):93-105 PMID: 17923090
  18. Stability of the hepatocyte nuclear factor 6 transcription factor requires acetylation by the CREB-binding protein coactivator.
    J Biol Chem. 2004 Oct 8;279(41):43070-6 PMID: 15304484
  19. E2F family members are differentially regulated by reversible acetylation.
    J Biol Chem. 2000 Apr 14;275(15):10887-92 PMID: 10753885
  20. DNA-damage-responsive acetylation of pRb regulates binding to E2F-1.
    EMBO Rep. 2006 Feb;7(2):192-8 PMID: 16374512
  21. Regulation and destabilization of HIF-1alpha by ARD1-mediated acetylation.
    Cell. 2002 Nov 27;111(5):709-20 PMID: 12464182
  22. Exit from G1 and S phase of the cell cycle is regulated by repressor complexes containing HDAC-Rb-hSWI/SNF and Rb-hSWI/SNF.
    Cell. 2000 Mar 31;101(1):79-89 PMID: 10778858
  23. p300-mediated acetylation of human transcriptional coactivator PC4 is inhibited by phosphorylation.
    J Biol Chem. 2001 May 18;276(20):16804-9 PMID: 11279157
  24. The androgen receptor acetylation site regulates cAMP and AKT but not ERK-induced activity.
    J Biol Chem. 2004 Jul 9;279(28):29436-49 PMID: 15123687
  25. Histone deacetylase 8 in neuroblastoma tumorigenesis.
    Clin Cancer Res. 2009 Jan 1;15(1):91-9 PMID: 19118036
  26. Histone deacetylase 4 controls chondrocyte hypertrophy during skeletogenesis.
    Cell. 2004 Nov 12;119(4):555-66 PMID: 15537544
  27. Reversible acetylation of non histone proteins: role in cellular function and disease.
    Subcell Biochem. 2007;41:193-212 PMID: 17484129
  28. Histone deacetylase inhibitors: current status and overview of recent clinical trials.
    Drugs. 2009 Oct 1;69(14):1911-34 PMID: 19747008
  29. Acetylation of RelA at discrete sites regulates distinct nuclear functions of NF-kappaB.
    EMBO J. 2002 Dec 2;21(23):6539-48 PMID: 12456660
  30. Histone deacetylase 3 associates with and represses the transcription factor GATA-2.
    Blood. 2001 Oct 1;98(7):2116-23 PMID: 11567998
  31. Acetylation of novel sites in the nucleosomal binding domain of chromosomal protein HMG-14 by p300 alters its interaction with nucleosomes.
    J Biol Chem. 2000 Apr 14;275(15):11514-20 PMID: 10753971
  32. Regulation of E2F1 activity by acetylation.
    EMBO J. 2000 Feb 15;19(4):662-71 PMID: 10675335
  33. Acetylation of p53 at lysine 373/382 by the histone deacetylase inhibitor depsipeptide induces expression of p21(Waf1/Cip1).
    Mol Cell Biol. 2006 Apr;26(7):2782-90 PMID: 16537920
  34. The diverse superfamily of lysine acetyltransferases and their roles in leukemia and other diseases.
    Nucleic Acids Res. 2004 Feb 11;32(3):959-76 PMID: 14960713
  35. Expression-based screening identifies the combination of histone deacetylase inhibitors and retinoids for neuroblastoma differentiation.
    Proc Natl Acad Sci U S A. 2008 Jul 15;105(28):9751-6 PMID: 18607002
  36. Histone deacetylase inhibitors activate p21(WAF1) expression via ATM.
    Cancer Res. 2003 Jun 1;63(11):2891-7 PMID: 12782595
  37. Acetylation of nuclear hormone receptor superfamily members: thyroid hormone causes acetylation of its own receptor by a mitogen-activated protein kinase-dependent mechanism.
    Steroids. 2005 May-Jun;70(5-7):444-9 PMID: 15862828
  38. Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase.
    EMBO J. 2004 Jun 16;23(12):2369-80 PMID: 15152190
  39. Down-regulation of nuclear factor kappaB is required for p53-dependent apoptosis in X-ray-irradiated mouse lymphoma cells and thymocytes.
    Cancer Res. 1999 Dec 15;59(24):6038-41 PMID: 10626786
  40. Overexpression of Smad7 results in severe pathological alterations in multiple epithelial tissues.
    EMBO J. 2002 Jun 3;21(11):2580-90 PMID: 12032071
  41. P/CAF associates with cyclin D1 and potentiates its activation of the estrogen receptor.
    Proc Natl Acad Sci U S A. 1999 May 11;96(10):5382-7 PMID: 10318892
  42. Histone deacetylases (HDACs): characterization of the classical HDAC family.
    Biochem J. 2003 Mar 15;370(Pt 3):737-49 PMID: 12429021
  43. HDACi--targets beyond chromatin.
    Cancer Lett. 2009 Aug 8;280(2):160-7 PMID: 19342155
  44. Will broad-spectrum histone deacetylase inhibitors be superseded by more specific compounds?
    Leukemia. 2007 Jan;21(1):61-5 PMID: 17109024
  45. Genetic dissection of glucocorticoid receptor function in mice.
    Curr Opin Genet Dev. 1998 Oct;8(5):532-8 PMID: 9794823
  46. Autoregulation of mouse histone deacetylase 1 expression.
    Mol Cell Biol. 2003 Oct;23(19):6993-7004 PMID: 12972616
  47. The ability of E1A to rescue ras-induced premature senescence and confer transformation relies on inactivation of both p300/CBP and Rb family proteins.
    Cancer Res. 2005 Sep 15;65(18):8298-307 PMID: 16166306
  48. High-mobility-group chromosomal proteins: architectural components that facilitate chromatin function.
    Prog Nucleic Acid Res Mol Biol. 1996;54:35-100 PMID: 8768072
  49. The FoxO code.
    Oncogene. 2008 Apr 7;27(16):2276-88 PMID: 18391970
  50. Histone deacetylase inhibitors induce VHL and ubiquitin-independent proteasomal degradation of hypoxia-inducible factor 1alpha.
    Mol Cell Biol. 2006 Mar;26(6):2019-28 PMID: 16507982
  51. Induction of interferon-stimulated gene expression and antiviral responses require protein deacetylase activity.
    Proc Natl Acad Sci U S A. 2004 Jun 29;101(26):9578-83 PMID: 15210966
  52. Histone deacetylase inhibitors sensitize prostate cancer cells to agents that produce DNA double-strand breaks by targeting Ku70 acetylation.
    Cancer Res. 2007 Jun 1;67(11):5318-27 PMID: 17545612
  53. Requirement of histone deacetylase activity for signaling by STAT1.
    J Biol Chem. 2004 Jul 16;279(29):30358-68 PMID: 15123634
  54. Sodium butyrate modifies the stabilizing complexes of tyrosine hydroxylase mRNA.
    Biochem Biophys Res Commun. 2007 Jul 20;359(1):15-9 PMID: 17524356
  55. Application of DNA methylation biomarkers for endometrial cancer management.
    Expert Rev Mol Diagn. 2008 Sep;8(5):607-16 PMID: 18785809
  56. Myosin phosphatase dephosphorylates HDAC7, controls its nucleocytoplasmic shuttling, and inhibits apoptosis in thymocytes.
    Genes Dev. 2007 Mar 15;21(6):638-43 PMID: 17369396
  57. Human class I histone deacetylase complexes show enhanced catalytic activity in the presence of ATP and co-immunoprecipitate with the ATP-dependent chaperone protein Hsp70.
    J Biol Chem. 2002 Mar 15;277(11):9590-7 PMID: 11777905
  58. Acetylation of the C terminus of Ku70 by CBP and PCAF controls Bax-mediated apoptosis.
    Mol Cell. 2004 Mar 12;13(5):627-38 PMID: 15023334
  59. Acetylation by histone acetyltransferase CREB-binding protein/p300 of STAT6 is required for transcriptional activation of the 15-lipoxygenase-1 gene.
    J Biol Chem. 2001 Nov 16;276(46):42753-60 PMID: 11509556
  60. Role of thioredoxin in the response of normal and transformed cells to histone deacetylase inhibitors.
    Proc Natl Acad Sci U S A. 2005 Jan 18;102(3):673-8 PMID: 15637150
  61. Regulation of histone deacetylase 4 and 5 and transcriptional activity by 14-3-3-dependent cellular localization.
    Proc Natl Acad Sci U S A. 2000 Jul 5;97(14):7835-40 PMID: 10869435
  62. SHP represses transcriptional activity via recruitment of histone deacetylases.
    Biochemistry. 2005 Apr 26;44(16):6312-20 PMID: 15835920
  63. In vitro acetylation of HMGB-1 and -2 proteins by CBP: the role of the acidic tail.
    Biochemistry. 2004 Mar 16;43(10):2935-40 PMID: 15005629
  64. Acetylation control of the retinoblastoma tumour-suppressor protein.
    Nat Cell Biol. 2001 Jul;3(7):667-74 PMID: 11433299
  65. Distinct p53 acetylation cassettes differentially influence gene-expression patterns and cell fate.
    J Cell Biol. 2006 May 22;173(4):533-44 PMID: 16717128
  66. Functional regulation of GATA-2 by acetylation.
    J Leukoc Biol. 2004 Mar;75(3):529-40 PMID: 15001660
  67. Histone deacetylase inhibitors regulate p21WAF1 gene expression at the post-transcriptional level in HepG2 cells.
    FEBS Lett. 2004 Jul 16;570(1-3):37-40 PMID: 15251435
  68. Histone deacetylase inhibitors decrease DNA methyltransferase-3B messenger RNA stability and down-regulate de novo DNA methyltransferase activity in human endometrial cells.
    Cancer Res. 2005 Apr 1;65(7):2684-9 PMID: 15805266
  69. PTEN acetylation modulates its interaction with PDZ domain.
    Cancer Res. 2008 Sep 1;68(17):6908-12 PMID: 18757404
  70. The modular nature of histone deacetylase HDAC4 confers phosphorylation-dependent intracellular trafficking.
    J Biol Chem. 2001 Sep 14;276(37):35042-8 PMID: 11470791
  71. Upregulation and nuclear recruitment of HDAC1 in hormone refractory prostate cancer.
    Prostate. 2004 May 1;59(2):177-89 PMID: 15042618
  72. ARDent about acetylation and deacetylation in hypoxia signalling.
    Trends Cell Biol. 2006 Dec;16(12):616-21 PMID: 17070052
  73. Structures of a histone deacetylase homologue bound to the TSA and SAHA inhibitors.
    Nature. 1999 Sep 9;401(6749):188-93 PMID: 10490031
  74. Stage-specific repression by the EKLF transcriptional activator.
    Mol Cell Biol. 2004 Dec;24(23):10416-24 PMID: 15542849
  75. HMG1 and 2, and related 'architectural' DNA-binding proteins.
    Trends Biochem Sci. 2001 Mar;26(3):167-74 PMID: 11246022
  76. The histone deacetylase inhibitor MS-275 promotes differentiation or apoptosis in human leukemia cells through a process regulated by generation of reactive oxygen species and induction of p21CIP1/WAF1 1.
    Cancer Res. 2003 Jul 1;63(13):3637-45 PMID: 12839953
  77. Phenylhexyl isothiocyanate has dual function as histone deacetylase inhibitor and hypomethylating agent and can inhibit myeloma cell growth by targeting critical pathways.
    J Hematol Oncol. 2008 Jun 09;1:6 PMID: 18577263
  78. Functional relevance of novel p300-mediated lysine 314 and 315 acetylation of RelA/p65.
    Nucleic Acids Res. 2008 Mar;36(5):1665-80 PMID: 18263619
  79. Post-translational modification of p53 in tumorigenesis.
    Nat Rev Cancer. 2004 Oct;4(10):793-805 PMID: 15510160
  80. Sirt2 interacts with 14-3-3 beta/gamma and down-regulates the activity of p53.
    Biochem Biophys Res Commun. 2008 Apr 11;368(3):690-5 PMID: 18249187
  81. Negative control of p53 by Sir2alpha promotes cell survival under stress.
    Cell. 2001 Oct 19;107(2):137-48 PMID: 11672522
  82. An acetylation site in the middle domain of Hsp90 regulates chaperone function.
    Mol Cell. 2007 Jan 12;25(1):151-9 PMID: 17218278
  83. Transcriptional repression by wild-type p53 utilizes histone deacetylases, mediated by interaction with mSin3a.
    Genes Dev. 1999 Oct 1;13(19):2490-501 PMID: 10521394
  84. Acetylation of HMG I(Y) by CBP turns off IFN beta expression by disrupting the enhanceosome.
    Mol Cell. 1998 Oct;2(4):457-67 PMID: 9809067
  85. Tumor suppressor SMAR1 mediates cyclin D1 repression by recruitment of the SIN3/histone deacetylase 1 complex.
    Mol Cell Biol. 2005 Oct;25(19):8415-29 PMID: 16166625
  86. The multiple activities of CtBP/BARS proteins: the Golgi view.
    Trends Cell Biol. 2006 Mar;16(3):167-73 PMID: 16483777
  87. Lysine acetylation targets protein complexes and co-regulates major cellular functions.
    Science. 2009 Aug 14;325(5942):834-40 PMID: 19608861
  88. Acetylation at a lysine residue adjacent to the CtBP binding motif within adenovirus 12 E1A causes structural disruption and limited reduction of CtBP binding.
    Virology. 2006 Nov 25;355(2):115-26 PMID: 16919702
  89. Up-regulation of p300 binding and p50 acetylation in tumor necrosis factor-alpha-induced cyclooxygenase-2 promoter activation.
    J Biol Chem. 2003 Feb 14;278(7):4770-7 PMID: 12471036
  90. Rational development of histone deacetylase inhibitors as anticancer agents: a review.
    Mol Pharmacol. 2005 Oct;68(4):917-32 PMID: 15955865
  91. Domain-selective small-molecule inhibitor of histone deacetylase 6 (HDAC6)-mediated tubulin deacetylation.
    Proc Natl Acad Sci U S A. 2003 Apr 15;100(8):4389-94 PMID: 12677000
  92. General transcriptional coactivator PC4 activates p53 function.
    Mol Cell Biol. 2004 Mar;24(5):2052-62 PMID: 14966284
  93. Aberrant expression of histone deacetylase 6 in oral squamous cell carcinoma.
    Int J Oncol. 2006 Jul;29(1):117-24 PMID: 16773191
  94. Acetylation is indispensable for p53 activation.
    Cell. 2008 May 16;133(4):612-26 PMID: 18485870
  95. De-repression of the p21 promoter in prostate cancer cells by an isothiocyanate via inhibition of HDACs and c-Myc.
    Int J Oncol. 2008 Aug;33(2):375-80 PMID: 18636159
  96. Acetylation of Foxo1 alters its DNA-binding ability and sensitivity to phosphorylation.
    Proc Natl Acad Sci U S A. 2005 Aug 9;102(32):11278-83 PMID: 16076959
  97. ACETYLATION AND METHYLATION OF HISTONES AND THEIR POSSIBLE ROLE IN THE REGULATION OF RNA SYNTHESIS.
    Proc Natl Acad Sci U S A. 1964 May;51:786-94 PMID: 14172992
  98. Molecular evolution of the histone deacetylase family: functional implications of phylogenetic analysis.
    J Mol Biol. 2004 Apr 16;338(1):17-31 PMID: 15050820
  99. Acetylation of the adenovirus-transforming protein E1A determines nuclear localization by disrupting association with importin-alpha.
    J Biol Chem. 2002 Oct 11;277(41):38755-63 PMID: 12161448
  100. Histone deacetylase inhibitors and paclitaxel cause synergistic effects on apoptosis and microtubule stabilization in papillary serous endometrial cancer cells.
    Mol Cancer Ther. 2006 Nov;5(11):2767-76 PMID: 17121923
  101. Differential roles for the coactivators CBP and p300 on TCF/beta-catenin-mediated survivin gene expression.
    Oncogene. 2005 May 19;24(22):3619-31 PMID: 15782138
  102. Explorative study on isoform-selective histone deacetylase inhibitors.
    Chem Pharm Bull (Tokyo). 2009 Sep;57(9):897-906 PMID: 19721249
  103. Discovery and development of SAHA as an anticancer agent.
    Oncogene. 2007 Feb 26;26(9):1351-6 PMID: 17322921
  104. Coordination of a transcriptional switch by HMGI(Y) acetylation.
    Science. 2001 Aug 10;293(5532):1133-6 PMID: 11498590
  105. The human Sir2 ortholog, SIRT2, is an NAD+-dependent tubulin deacetylase.
    Mol Cell. 2003 Feb;11(2):437-44 PMID: 12620231
  106. Studies of acetylation and deacetylation in high mobility group proteins. Identification of the sites of acetylation in HMG-1.
    J Biol Chem. 1979 Nov 25;254(22):11577-83 PMID: 500660
  107. A phase 1 pharmacokinetic and pharmacodynamic study of the histone deacetylase inhibitor belinostat in patients with advanced solid tumors.
    Clin Cancer Res. 2008 Feb 1;14(3):804-10 PMID: 18245542
  108. OSU-HDAC42, a histone deacetylase inhibitor, blocks prostate tumor progression in the transgenic adenocarcinoma of the mouse prostate model.
    Cancer Res. 2008 May 15;68(10):3999-4009 PMID: 18483287
  109. Dimethyl sulfoxide to vorinostat: development of this histone deacetylase inhibitor as an anticancer drug.
    Nat Biotechnol. 2007 Jan;25(1):84-90 PMID: 17211407
  110. Anti-estrogenic actions of histone deacetylase inhibitors in MCF-7 breast cancer cells.
    Endocr Relat Cancer. 2007 Dec;14(4):1021-8 PMID: 18045953
  111. Transcriptional control at regulatory checkpoints by histone deacetylases: molecular connections between cancer and chromatin.
    Hum Mol Genet. 2001 Apr;10(7):693-8 PMID: 11257101
  112. Histone deacetylase as a therapeutic target.
    Trends Endocrinol Metab. 2001 Sep;12(7):294-300 PMID: 11504668
  113. Promising antitumor activity with MGCD0103, a novel isotype-selective histone deacetylase inhibitor.
    Expert Opin Investig Drugs. 2008 Aug;17(8):1247-54 PMID: 18616420
  114. Valproic acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells.
    EMBO J. 2001 Dec 17;20(24):6969-78 PMID: 11742974
  115. Phosphatase inhibition leads to histone deacetylases 1 and 2 phosphorylation and disruption of corepressor interactions.
    J Biol Chem. 2002 May 31;277(22):19618-26 PMID: 11919195
  116. Post-activation turn-off of NF-kappa B-dependent transcription is regulated by acetylation of p65.
    J Biol Chem. 2003 Jan 24;278(4):2758-66 PMID: 12419806
  117. HDAC6 deacetylation of tubulin modulates dynamics of cellular adhesions.
    J Cell Sci. 2007 Apr 15;120(Pt 8):1469-79 PMID: 17389687
  118. Overexpression of histone deacetylase 1 confers resistance to sodium butyrate-mediated apoptosis in melanoma cells through a p53-mediated pathway.
    Cancer Res. 2004 Nov 1;64(21):7706-10 PMID: 15520174
  119. Hepatic insulin resistance induced by prenatal alcohol exposure is associated with reduced PTEN and TRB3 acetylation in adult rat offspring.
    Am J Physiol Regul Integr Comp Physiol. 2008 Jun;294(6):R1797-806 PMID: 18385463
  120. DNA damage-dependent acetylation of p73 dictates the selective activation of apoptotic target genes.
    Mol Cell. 2002 Jan;9(1):175-86 PMID: 11804596
  121. Regulation of transcription factor YY1 by acetylation and deacetylation.
    Mol Cell Biol. 2001 Sep;21(17):5979-91 PMID: 11486036
  122. Structure of the hepatocyte nuclear factor 6alpha and its interaction with DNA.
    J Biol Chem. 2004 Aug 6;279(32):33928-36 PMID: 15169783
  123. Acetylation regulates subcellular localization of the Wnt signaling nuclear effector POP-1.
    Genes Dev. 2003 Mar 15;17(6):717-22 PMID: 12651889
  124. Unlocking the mechanisms of transcription factor YY1: are chromatin modifying enzymes the key?
    Gene. 1999 Aug 20;236(2):197-208 PMID: 10452940
  125. Site-specific acetylation by p300 or CREB binding protein regulates erythroid Krüppel-like factor transcriptional activity via its interaction with the SWI-SNF complex.
    Mol Cell Biol. 2001 Apr;21(7):2413-22 PMID: 11259590
  126. MDM2-HDAC1-mediated deacetylation of p53 is required for its degradation.
    EMBO J. 2002 Nov 15;21(22):6236-45 PMID: 12426395
  127. Suberoylanilide hydroxamic acid (vorinostat) represses androgen receptor expression and acts synergistically with an androgen receptor antagonist to inhibit prostate cancer cell proliferation.
    Mol Cancer Ther. 2007 Jan;6(1):51-60 PMID: 17218635
  128. Essential function of histone deacetylase 1 in proliferation control and CDK inhibitor repression.
    EMBO J. 2002 Jun 3;21(11):2672-81 PMID: 12032080
  129. Valproic acid inhibits angiogenesis in vitro and in vivo.
    Mol Pharmacol. 2004 Mar;65(3):520-7 PMID: 14978230
  130. Modulation of HMG-N2 binding to chromatin by butyrate-induced acetylation in human colon adenocarcinoma cells.
    Int J Cancer. 2002 Feb 10;97(5):567-73 PMID: 11807779
  131. Regulation of histone deacetylase activities.
    J Cell Biochem. 2004 Sep 1;93(1):57-67 PMID: 15352162
  132. Transcriptional regulation by the acetylation of nonhistone proteins in humans -- a new target for therapeutics.
    IUBMB Life. 2005 Mar;57(3):137-49 PMID: 16036576
  133. Diallyl disulfide (DADS) increases histone acetylation and p21(waf1/cip1) expression in human colon tumor cell lines.
    Carcinogenesis. 2004 Jul;25(7):1227-36 PMID: 14976134
  134. Epigenetic therapy of cancer: past, present and future.
    Nat Rev Drug Discov. 2006 Jan;5(1):37-50 PMID: 16485345
  135. Forced evolution of a regulatory RNA helix in the HIV-1 genome.
    Nucleic Acids Res. 1997 Mar 1;25(5):940-7 PMID: 9023102
  136. The histone deacetylase inhibitor NVP-LAQ824 inhibits angiogenesis and has a greater antitumor effect in combination with the vascular endothelial growth factor receptor tyrosine kinase inhibitor PTK787/ZK222584.
    Cancer Res. 2004 Sep 15;64(18):6626-34 PMID: 15374977
  137. Acetylation of steroidogenic factor 1 protein regulates its transcriptional activity and recruits the coactivator GCN5.
    J Biol Chem. 2001 Oct 5;276(40):37659-64 PMID: 11479297
  138. Acetylation of adenovirus E1A regulates binding of the transcriptional corepressor CtBP.
    Proc Natl Acad Sci U S A. 2000 Dec 19;97(26):14323-8 PMID: 11114158
  139. Deacetylation of p53 modulates its effect on cell growth and apoptosis.
    Nature. 2000 Nov 16;408(6810):377-81 PMID: 11099047
  140. Regulation of protein turnover by acetyltransferases and deacetylases.
    Biochimie. 2008 Feb;90(2):306-12 PMID: 17681659
  141. Trichostatin A down-regulate DNA methyltransferase 1 in Jurkat T cells.
    Cancer Lett. 2007 Feb 8;246(1-2):313-7 PMID: 16624484
  142. Auto-acetylation of transcription factors as a control mechanism in gene expression.
    Cell Cycle. 2004 Feb;3(2):114-5 PMID: 14712067
  143. Identifying molecular targets mediating the anticancer activity of histone deacetylase inhibitors: a work in progress.
    Curr Cancer Drug Targets. 2002 Dec;2(4):337-53 PMID: 12470210
  144. Potent and specific inhibition of mammalian histone deacetylase both in vivo and in vitro by trichostatin A.
    J Biol Chem. 1990 Oct 5;265(28):17174-9 PMID: 2211619
  145. Acetylation of Sirt2 by p300 attenuates its deacetylase activity.
    Biochem Biophys Res Commun. 2008 Oct 31;375(4):576-80 PMID: 18722353
  146. Activation of p53 sequence-specific DNA binding by acetylation of the p53 C-terminal domain.
    Cell. 1997 Aug 22;90(4):595-606 PMID: 9288740
  147. Class II histone deacetylases are associated with VHL-independent regulation of hypoxia-inducible factor 1 alpha.
    Cancer Res. 2006 Sep 1;66(17):8814-21 PMID: 16951198
  148. Regulation of SV40 large T-antigen stability by reversible acetylation.
    Oncogene. 2006 Nov 30;25(56):7391-400 PMID: 16767160
  149. Acetylation of Stat1 modulates NF-kappaB activity.
    Genes Dev. 2006 Feb 15;20(4):473-85 PMID: 16481475
  150. Posttranslational modification and microtubule stability.
    J Cell Biol. 1987 Nov;105(5):2167-77 PMID: 3316248
  151. Chemoprotection by sulforaphane: keep one eye beyond Keap1.
    Cancer Lett. 2006 Feb 28;233(2):208-18 PMID: 16520150
  152. A novel mechanism of chemoprotection by sulforaphane: inhibition of histone deacetylase.
    Cancer Res. 2004 Aug 15;64(16):5767-74 PMID: 15313918
  153. Histone deacetylase inhibitors: molecular mechanisms of action.
    Oncogene. 2007 Aug 13;26(37):5541-52 PMID: 17694093
  154. Treatment of uterine papillary serous carcinoma with paclitaxel.
    Gynecol Oncol. 2001 Jul;82(1):156-61 PMID: 11426978
  155. Acetylation of MyoD directed by PCAF is necessary for the execution of the muscle program.
    Mol Cell. 1999 Nov;4(5):725-34 PMID: 10619020
  156. Acetylation of the HIV-1 Tat protein by p300 is important for its transcriptional activity.
    Curr Biol. 1999 Dec 16-30;9(24):1489-92 PMID: 10607594
  157. Lysine acetylation: codified crosstalk with other posttranslational modifications.
    Mol Cell. 2008 Aug 22;31(4):449-461 PMID: 18722172
  158. Phase II multi-institutional trial of the histone deacetylase inhibitor romidepsin as monotherapy for patients with cutaneous T-cell lymphoma.
    J Clin Oncol. 2009 Nov 10;27(32):5410-7 PMID: 19826128
  159. HIV-1 tat transcriptional activity is regulated by acetylation.
    EMBO J. 1999 Nov 1;18(21):6106-18 PMID: 10545121
  160. Role of phosphorylation in p53 acetylation and PAb421 epitope recognition in baculoviral and mammalian expressed proteins.
    FEBS J. 2005 Apr;272(7):1669-75 PMID: 15794754
  161. Shaping the nuclear action of NF-kappaB.
    Nat Rev Mol Cell Biol. 2004 May;5(5):392-401 PMID: 15122352
  162. Nalpha -terminal acetylation of eukaryotic proteins.
    J Biol Chem. 2000 Nov 24;275(47):36479-82 PMID: 11013267
  163. HDAC6 deacetylase activity links the tubulin cytoskeleton with immune synapse organization.
    Immunity. 2004 Apr;20(4):417-28 PMID: 15084271
  164. Histone deacetylases inhibitors as anti-angiogenic agents altering vascular endothelial growth factor signaling.
    Oncogene. 2002 Jan 17;21(3):427-36 PMID: 11821955
  165. MEF2C transcription factor controls chondrocyte hypertrophy and bone development.
    Dev Cell. 2007 Mar;12(3):377-89 PMID: 17336904
  166. Acetylation and deacetylation of non-histone proteins.
    Gene. 2005 Dec 19;363:15-23 PMID: 16289629
  167. n-Butyrate causes histone modification in HeLa and Friend erythroleukaemia cells.
    Nature. 1977 Aug 4;268(5619):462-4 PMID: 268489
  168. Isolation and characterization of cDNAs corresponding to an additional member of the human histone deacetylase gene family.
    J Biol Chem. 1997 Oct 31;272(44):28001-7 PMID: 9346952
  169. Histone deacetylase inhibitors as a new weapon in the arsenal of differentiation therapies of cancer.
    Cancer Lett. 2009 Aug 8;280(2):134-44 PMID: 19345000
  170. Specific acetylation of chromosomal protein HMG-17 by PCAF alters its interaction with nucleosomes.
    Mol Cell Biol. 1999 May;19(5):3466-73 PMID: 10207070
  171. Epigenetic therapy in cancer: molecular background and clinical development of histone deacetylase and DNA methyltransferase inhibitors.
    IDrugs. 2007 Aug;10(8):557-61 PMID: 17665331
  172. Stat3 dimerization regulated by reversible acetylation of a single lysine residue.
    Science. 2005 Jan 14;307(5707):269-73 PMID: 15653507
  173. Post-initiation modulating effects of allyl sulfides in rat hepatocarcinogenesis.
    Food Chem Toxicol. 2004 Sep;42(9):1479-85 PMID: 15234078
  174. HDAC6 is a microtubule-associated deacetylase.
    Nature. 2002 May 23;417(6887):455-8 PMID: 12024216
  175. The cytoplasmic deacetylase HDAC6 is required for efficient oncogenic tumorigenesis.
    Cancer Res. 2008 Sep 15;68(18):7561-9 PMID: 18794144
  176. Class II histone deacetylases: from sequence to function, regulation, and clinical implication.
    Mol Cell Biol. 2005 Apr;25(8):2873-84 PMID: 15798178
  177. Sirtuin functions in health and disease.
    Mol Endocrinol. 2007 Aug;21(8):1745-55 PMID: 17456799
  178. Mechanism of active transcriptional repression by the retinoblastoma protein.
    Nature. 1995 Jun 29;375(6534):812-5 PMID: 7596417
  179. HDAC7, a thymus-specific class II histone deacetylase, regulates Nur77 transcription and TCR-mediated apoptosis.
    Immunity. 2003 May;18(5):687-98 PMID: 12753745
  180. Human SirT1 interacts with histone H1 and promotes formation of facultative heterochromatin.
    Mol Cell. 2004 Oct 8;16(1):93-105 PMID: 15469825
  181. Histone deacetylases specifically down-regulate p53-dependent gene activation.
    J Biol Chem. 2000 Jul 7;275(27):20436-43 PMID: 10777477
  182. Inhibition of histone deacetylase 2 increases apoptosis and p21Cip1/WAF1 expression, independent of histone deacetylase 1.
    Cell Death Differ. 2005 Apr;12(4):395-404 PMID: 15665816
  183. Dual regulation of c-Myc by p300 via acetylation-dependent control of Myc protein turnover and coactivation of Myc-induced transcription.
    Mol Cell Biol. 2005 Dec;25(23):10220-34 PMID: 16287840
  184. Control of Smad7 stability by competition between acetylation and ubiquitination.
    Mol Cell. 2002 Sep;10(3):483-93 PMID: 12408818
  185. Histone deacetylase inhibitors: signalling towards p21cip1/waf1.
    Int J Biochem Cell Biol. 2007;39(7-8):1367-74 PMID: 17412634
  186. Monocytic cells hyperacetylate chromatin protein HMGB1 to redirect it towards secretion.
    EMBO J. 2003 Oct 15;22(20):5551-60 PMID: 14532127
  187. Regulation of human SRY subcellular distribution by its acetylation/deacetylation.
    EMBO J. 2004 Aug 18;23(16):3336-45 PMID: 15297880
  188. The balance between acetylation and deacetylation controls Smad7 stability.
    J Biol Chem. 2005 Jun 10;280(23):21797-803 PMID: 15831498
  189. Histone deacetylase 7 maintains vascular integrity by repressing matrix metalloproteinase 10.
    Cell. 2006 Jul 28;126(2):321-34 PMID: 16873063
Article Info
Journal
Expert review of anticancer therapy
Abbr.
Expert Rev Anticancer Ther
ISSN
1744-8328
DOI
10.1586/era.10.62
Published
2010-06-00
Pages
935-54
Language
English
Region
England
NLM ID
101123358
PMCID
PMC3273412
Subset
IM
Grants
NICHD NIH HHS · R01 HD041577 · United States
NICHD NIH HHS · R01 HD041577-05 · United States
NICHD NIH HHS · R01 HD041577-06 · United States
NICHD NIH HHS · R01 HD 41577 · United States
External Links
PubMed source DOI: 10.1586/era.10.62 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2