Histone deacetylase (primarily Class I and HDAC6) (HDAC)

Histone deacetylases (HDACs) are essential enzymes that catalyze the removal of acetyl groups from lysine residues on both histone and non-histone proteins. Class I HDACs (HDAC1, 2, 3, and 8) are predominantly nuclear and play a critical role in regulating chromatin structure and gene transcription, often acting as transcriptional corepressors (UniProt: P50851). HDAC6, a Class IIb member, is primarily localized in the cytoplasm where it regulates diverse processes such as microtubule-dependent transport and the degradation of misfolded proteins via the aggresome pathway (UniProt: Q9UBN7). Overexpression or dysregulation of these enzymes is frequently observed in various malignancies, leading to the silencing of tumor suppressor genes and promotion of cell survival (PubMed: 22429471). Consequently, HDACs have become major therapeutic targets, particularly in oncology. Drugs targeting Class I and HDAC6, such as Vorinostat and Panobinostat, work by inducing hyperacetylation, which results in cell cycle arrest, differentiation, and apoptosis of malignant cells (NIH: StatPearls - Histone Deacetylase Inhibitors). Beyond cancer, these enzymes are being investigated for their roles in neurodegenerative diseases and inflammatory conditions due to their broad impact on cellular homeostasis (PubMed: 23911236).

Other names

HDACLysine deacetylaseHDHDC

HDAC inhibitors bind to the zinc-dependent catalytic site of histone deacetylases, blocking the removal of acetyl groups from lysine residues on histones and non-histone proteins. This leads to hyperacetylation, which promotes an open chromatin structure (euchromatin) and reactivates the expression of tumor suppressor genes, induces cell cycle arrest, and triggers apoptosis. Inhibition of HDAC6 specifically increases the acetylation of cytoplasmic proteins like alpha-tubulin, disrupting cell motility and the aggresome-mediated degradation of misfolded proteins (PubMed: 22429471; NIH: StatPearls - Histone Deacetylase Inhibitors).