Histone deacetylase 1 (HDAC1), Histone deacetylase 3 (HDAC3), and Histone deacetylase 8 (HDAC8) (HDAC1/3/8)

Histone deacetylase 1 (HDAC1), Histone deacetylase 3 (HDAC3), and Histone deacetylase 8 (HDAC8) are enzymes belonging to the Class I histone deacetylase family, primarily responsible for removing acetyl groups from lysine residues on histone proteins [1, 2, 3]. This deacetylation process promotes a condensed chromatin state, which generally leads to the transcriptional silencing of genes involved in cell cycle regulation, differentiation, and apoptosis [4]. While HDAC1 and HDAC3 typically function as part of large multi-protein co-repressor complexes like CoREST or NCoR/SMRT, HDAC8 can operate as a monomer and has distinct roles in both nuclear and cytoplasmic signaling [4, 5]. In various cancers, these enzymes are frequently overexpressed, contributing to the epigenetic silencing of tumor suppressor genes and promoting oncogenic transformation [6]. Therapeutic targeting of HDAC1, 3, and 8 with small molecule inhibitors aims to reverse these epigenetic changes, inducing hyperacetylation and restoring the expression of genes that trigger cell cycle arrest and programmed cell death [7]. Drugs such as Vorinostat and Romidepsin are currently utilized in the treatment of cutaneous T-cell lymphoma, while newer, more selective inhibitors are being explored to minimize the systemic toxicities associated with pan-HDAC inhibition [8]. Sources: [1] UniProt Q13547 (HDAC1) [2] UniProt O15379 (HDAC3) [3] UniProt Q9BY41 (HDAC8) [4] Haberland et al., Nature Reviews Genetics, 2009 (PMID: 19238173) [5] West and Johnstone, Journal of Clinical Investigation, 2014 (PMID: 24382344) [6] Falkenberg and Johnstone, Nature Reviews Drug Discovery, 2014 (PMID: 25124585) [7] Eckschlager et al., International Journal of Molecular Sciences, 2017 (PMID: 28841160) [8] FDA Drug Labels (Vorinostat, Romidepsin)

Other names

Class I histone deacetylasesHD1RPD3HDAC1HDAC3HDAC8

Inhibition of the zinc-dependent catalytic domain of histone deacetylases, preventing the removal of acetyl groups from lysine residues on histones and non-histone proteins, leading to hyperacetylation and transcriptional activation of suppressed genes.