HDAC1, HDAC2, HDAC3, HDAC10

Histone deacetylases 1/2/3/10 are zinc-dependent enzymes that catalyze the removal of acetyl groups from lysine residues on histone and non-histone proteins, tightly regulating gene expression by condensing chromatin and repressing transcription. HDAC1, HDAC2, and HDAC3 are class I HDACs, predominantly nuclear and highly expressed, serving crucial roles in cell cycle progression, differentiation, and survival. HDAC10 is a class IIb HDAC with specialization as a polyamine deacetylase and also involved in transcriptional repression and DNA damage repair. Dysregulation or overexpression of these HDACs is implicated in cancer and other diseases, making them important therapeutic targets for HDAC inhibitor drugs. Their biological functions span chromatin remodeling, transcriptional control, apoptosis regulation, and cellular stress responses. However, clinical use of their inhibitors is challenged by off-target effects and dose-limiting toxicities.

Other names

Rpd3 homologHda1-like protein (class I HDAC)Hda1-like protein (class IIb HDAC)polyamine deacetylase

HDAC inhibitors bind and block the deacetylase activity of HDAC enzymes, leading to hyperacetylation of histones and non-histone proteins, resulting in chromatin relaxation, enhanced gene expression of tumor suppressors, and induction of cell cycle arrest, apoptosis, and differentiation