KDACs

KDACs, or Lysine Deacetylases, are a family of enzymes that remove acetyl groups from lysine residues in proteins. This process, known as deacetylation, is a crucial post-translational modification that plays a significant role in regulating a wide array of cellular functions. Histone deacetylation, a prominent example, directly impacts gene expression by altering chromatin structure, making DNA more or less accessible for transcription. Beyond histones, KDACs target numerous non-histone proteins, influencing their activity, stability, and localization.

The KDAC family is broadly classified into four classes based on their sequence homology and catalytic mechanisms. Class I KDACs are closely related to yeast Rpd3, Class II KDACs are homologous to yeast Hda1, Class III KDACs are sirtuins, which require NAD+ as a cofactor, and Class IV KDACs are represented by a single enzyme, HDAC11, which shares features of both Class I and II. Dysregulation of KDAC activity has been implicated in various diseases, including cancer, neurological disorders, and metabolic diseases. Consequently, KDAC inhibitors have emerged as a significant area of therapeutic research, with several drugs already approved for certain types of cancer. Their mechanisms of action are diverse, often leading to cell cycle arrest, differentiation, and apoptosis in cancer cells.