Histone deacetylases (HDACs) are enzymes that catalyze the removal of acetyl functional groups from the lysine residues of both histone and nonhistone proteins. In humans, there are 18 HDAC enzymes that use either zinc- or NAD+-dependent mechanisms to deacetylate acetyl lysine substrates. The Class I proteins (HDAC1, HDAC2, HDAC3, and HDAC8) have sequence similarity to the yeast Rpd3 protein. The Class II proteins (HDAC4, HDAC5, HDAC6, HDAC7, HDAC9, and HDAC10) have sequence similarity to the yeast Hda1 protein. The Class III proteins (SIRT1, SIRT2, SIRT3, SIRT4, SIRT5, SIRT6, and SIRT7) have sequence similarity to the yeast Sir2 protein. The Class IV protein (HDAC11) shares sequence similarity to both Class I and II proteins. 
HDAC1 is phosphorylated by cAMP-dependent kinase PKA and protein kinase CK2. HDAC3 can also be phosphorylated by GSK-3b, and inhibition of GSK-3b protects against HDAC3-induced neurotoxicity. The subcellular localization is regulated by the binding of the 14-3-3 proteins to a phosphorylated HDAC4. . Aurora A (AurA) phosphorylates HDAC6 to activate tubulin deacetylase activity. Cell cycle –dependent kinase cyclin B/Cdk1 phosphorylates SIRT1,  JNK1 phosphorylates SIRT1 at S27, S47, and T530, and this phosphorylation of SIRT1 increased its nuclear localization and enzymatic activity. HDACs modulate the function of many proteins through nonhistone deacetylation, HDACs potentially play a role in nearly every aspect of health and disease. Numerous reports document the involvement of HDACs in cancer, neurodegenerative diseases, metabolic disorders, inflammatory diseases, immunological disorders, cardiac diseases, and pulmonary diseases.


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