Histone deacetylases class I, II, and IV (HDACs)

Histone deacetylases (HDACs) of classes I, II, and IV are a group of 11 zinc-dependent enzymes that catalyze the removal of acetyl groups from lysine residues on both histone and non-histone proteins [1, 2, 4]. Class I includes HDAC1, 2, 3, and 8; Class II is divided into IIa (HDAC4, 5, 7, 9) and IIb (HDAC6, 10); and Class IV consists of HDAC11 [1, 11, 15, 23]. By deacetylating histones, these enzymes promote a condensed chromatin structure (heterochromatin), which generally leads to the transcriptional repression of genes involved in cell cycle regulation, differentiation, and apoptosis [5, 17, 19, 20]. Beyond histones, they also target various non-histone proteins such as p53, Hsp90, and alpha-tubulin, thereby influencing protein stability, localization, and activity [1, 2, 21, 22]. Dysregulation or overexpression of these HDACs is frequently observed in various cancers, where they contribute to the silencing of tumor suppressor genes and promote oncogenic pathways [4, 9, 12, 21]. Consequently, they have become significant therapeutic targets, with several HDAC inhibitors (HDACis) like vorinostat and romidepsin approved for the treatment of hematological malignancies [4, 21, 22]. Ongoing research also explores their potential in treating solid tumors, neurodegenerative disorders, and inflammatory conditions [3, 8, 23].

Other names

HDAC [1, 19, 21]Lysine deacetylases [1, 2, 17, 20]KDAC [17, 20]Classical histone deacetylases [2, 10, 20, 23]Zinc-dependent histone deacetylases [1, 4, 8, 10, 15, 19, 20, 21, 22, 23]

Inhibition of the zinc-dependent catalytic domain of HDAC enzymes, preventing the removal of acetyl groups from lysine residues on histones and non-histone proteins [1, 10, 22]. This leads to hyperacetylation, chromatin relaxation, and the re-expression of genes that induce cell cycle arrest and apoptosis [4, 6, 23].