Histone deacetylase 1, Histone deacetylase 2, Histone deacetylase 3, and Histone deacetylase 6 (HDAC1/2/3/6)

Histone deacetylase 1 (HDAC1), Histone deacetylase 2 (HDAC2), Histone deacetylase 3 (HDAC3), and Histone deacetylase 6 (HDAC6) are key enzymes involved in the epigenetic regulation of gene expression and the post-translational modification of non-histone proteins [4, 9, 14]. HDAC1, 2, and 3 are Class I HDACs primarily located in the nucleus, where they function as catalytic components of multi-protein co-repressor complexes to regulate chromatin structure, cell cycle progression, and DNA repair [4, 12, 14]. In contrast, HDAC6 is a Class IIb HDAC predominantly found in the cytoplasm, where it modulates the acetylation of substrates such as alpha-tubulin, Hsp90, and cortactin, thereby influencing intracellular transport, protein degradation, and cell motility [17, 18, 19]. Dysregulation of these isoforms is frequently observed in various malignancies, leading to the silencing of tumor suppressor genes and the promotion of cell survival and proliferation [6, 10, 20]. Consequently, this specific combination of HDACs is a major therapeutic target in oncology, with several approved drugs like vorinostat and belinostat acting as inhibitors to induce apoptosis and inhibit tumor growth [5, 13, 16]. Beyond cancer, these enzymes are also implicated in neurodegenerative diseases and inflammatory conditions, making them versatile targets for drug development [1, 7, 17].

Other names

Class I and IIb histone deacetylasesHDAC1/2/3/6Histone deacetylase 1/2/3/6HDAC1, HDAC2, HDAC3, and HDAC6

Inhibition of histone and non-histone protein deacetylation, leading to increased acetylation of histones (promoting open chromatin and gene transcription) and non-histone proteins (e.g., alpha-tubulin, p53, Hsp90), resulting in cell cycle arrest, apoptosis, and impaired protein degradation pathways [4, 6, 13, 19].