Histone deacetylase class I and class IIb (HDAC I/IIb)

Histone deacetylases (HDACs) are a group of enzymes responsible for the removal of acetyl groups from lysine residues on both histone and non-histone proteins, a process that generally leads to chromatin condensation and transcriptional repression (UniProt, 2024). Class I HDACs (comprising HDAC1, 2, 3, and 8) are predominantly located in the nucleus and are essential for regulating the cell cycle and survival, while Class IIb HDACs (HDAC6 and 10) are unique for having two catalytic domains and regulating cytoplasmic targets like alpha-tubulin and heat shock proteins (NCBI, 2023). Dysregulation of these enzymes is a hallmark of many cancers, where they contribute to the silencing of tumor suppressor genes and the promotion of tumor growth and metastasis (PubMed, 2022). Therapeutic targeting of Class I and IIb HDACs with small molecule inhibitors, such as Vorinostat or Panobinostat, involves binding to the zinc-containing catalytic site to block enzymatic activity, thereby inducing apoptosis and differentiation in cancer cells (StatPearls, 2023). While effective in treating certain hematological malignancies like cutaneous T-cell lymphoma and multiple myeloma, these inhibitors are associated with significant side effects, including myelosuppression and cardiac toxicity, which necessitates careful patient monitoring (NIH, 2024).

Other names

Class I and IIb HDACsZinc-dependent histone deacetylases class I and IIbHDAC1, 2, 3, 8, 6, and 10

Inhibition of the catalytic activity of zinc-dependent histone deacetylases, leading to hyperacetylation of histones and non-histone proteins, which induces cell cycle arrest, differentiation, and apoptosis.