Histone deacetylase 2 and Histone deacetylase 3 (HDAC2 and HDAC3)

Histone deacetylase 2 and Histone deacetylase 3 are members of the class I family of zinc-dependent histone deacetylases. These enzymes catalyze the removal of acetyl groups from ε-N-acetyl lysine residues on both histones and non-histone proteins. By removing these acetyl groups, they promote chromatin condensation and transcriptional repression. Beyond their role in gene silencing through chromatin remodeling, they also regulate numerous cellular processes by modifying non-histone substrates involved in signal transduction pathways. Dysregulation or overexpression is associated with several human diseases including cancer and neurodegeneration. They are validated therapeutic targets for small-molecule inhibitors used primarily in oncology.

Other names

HDAC2HDAC3Class I histone deacetylaseRpd3-like protein (homologous to yeast Rpd3)

Drugs targeting these molecules typically act as competitive inhibitors of the zinc-dependent catalytic site, blocking the removal of acetyl groups from lysine residues on histones/non-histones. This leads to increased acetylation, relaxed chromatin structure, reactivation of silenced genes (including tumor suppressors), cell cycle arrest, differentiation or apoptosis in cancer cells.