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Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).
Histone deacetylases act as erasers of epigenetic acetylation marks on lysine residues in histones. Removal of the acetyl groups facilitates tighter packing of chromatin (heterochromatin formation) leading to transcriptional repression.
The histone deacetylase family has been classified in to five subfamilies based on phylogenetic comparison with yeast homologues:
Class I contains HDACs 1, 2, 3 and 8
Class IIa contains HDACs 4, 5, 7 and 9
Class IIb contains HDACs 6 and 10
Class III contains the sirtuins (SIRT1-7)
Class IV contains only HDAC11.
Classes I, II and IV use Zn+ as a co-factor, whereas catalysis by Class III enzymes requires NAD+ as a co-factor, and members of this subfamily have ADP-ribosylase activity in addition to protein deacetylase function .
HDACs have more general protein deacetylase activity, being able to deacetylate lysine residues in non-histone proteins  such as microtubules , the hsp90 chaperone  and the tumour suppressor p53 .
Dysregulated HDAC activity has been identified in cancer cells and tumour tissues [12,19], making HDACs attractive molecular targets in the search for novel mechanisms to treat cancer . Several small molecule HDAC inhibitors are already approved for clinical use: romidepsin, belinostat, vorinostat, panobinostat, belinostat, valproic acid and tucidinostat. HDACs and HDAC inhibitors currently in development as potential anti-cancer therapeutics are reviewed by Simó-Riudalbas and Esteller (2015) .
* Key recommended reading is highlighted with an asterisk
Butler JS, Koutelou E, Schibler AC, Dent SY. (2012) Histone-modifying enzymes: regulators of developmental decisions and drivers of human disease. Epigenomics, 4 (2): 163-77. [PMID:22449188]
Tang J, Yan H, Zhuang S. (2013) Histone deacetylases as targets for treatment of multiple diseases. Clin. Sci., 124 (11): 651-62. [PMID:23414309]
Walkinshaw DR, Tahmasebi S, Bertos NR, Yang XJ. (2008) Histone deacetylases as transducers and targets of nuclear signaling. J. Cell. Biochem., 104 (5): 1541-52. [PMID:18425769]
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3. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M. (2009) Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science, 325 (5942): 834-40. [PMID:19608861]
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11. Kovacs JJ, Murphy PJ, Gaillard S, Zhao X, Wu JT, Nicchitta CV, Yoshida M, Toft DO, Pratt WB, Yao TP. (2005) HDAC6 regulates Hsp90 acetylation and chaperone-dependent activation of glucocorticoid receptor. Mol. Cell, 18 (5): 601-7. [PMID:15916966]
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18. Phiel CJ, Zhang F, Huang EY, Guenther MG, Lazar MA, Klein PS. (2001) Histone deacetylase is a direct target of valproic acid, a potent anticonvulsant, mood stabilizer, and teratogen. J. Biol. Chem., 276 (39): 36734-41. [PMID:11473107]
19. Ropero S, Esteller M. (2007) The role of histone deacetylases (HDACs) in human cancer. Mol Oncol, 1 (1): 19-25. [PMID:19383284]
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23. Solomon JM, Pasupuleti R, Xu L, McDonagh T, Curtis R, DiStefano PS, Huber LJ. (2006) Inhibition of SIRT1 catalytic activity increases p53 acetylation but does not alter cell survival following DNA damage. Mol. Cell. Biol., 26 (1): 28-38. [PMID:16354677]
24. Wang H, Lim ZY, Zhou Y, Ng M, Lu T, Lee K, Sangthongpitag K, Goh KC, Wang X, Wu X et al.. (2010) Acylurea connected straight chain hydroxamates as novel histone deacetylase inhibitors: Synthesis, SAR, and in vivo antitumor activity. Bioorg. Med. Chem. Lett., 20 (11): 3314-21. [PMID:20451378]
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Database page citation:
3.5.1.- Histone deacetylases (HDACs). Accessed on 29/04/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=848.
Concise Guide to PHARMACOLOGY citation:
Alexander SPH, Fabbro D, Kelly E, Marrion N, Peters JA, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Southan C, Davies JA and CGTP Collaborators (2015) The Concise Guide to PHARMACOLOGY 2015/16: Enzymes. Br J Pharmacol. 172: 6024-6109.