Mammalian histone deacetylases (HDACs) catalyze the removal of acetyl groups from the ε-amino group of lysine residues and are divided into four distinct subclasses, which comprise three
AR-42 HDAC of non-sirtuin HDACs (class I, II and IV HDACs) and the sirtuins (class III HDACs), which received their name based on their homology with the yeast Sir2 protein [1]. The main distinguishing feature, that discriminates the sirtuins from other HDACs, is their exceptional enzymatic mechanism. While class I, II and IV HDACs are Zn2+-dependent hydrolases, the sirtuins exhibit a unique NAD-dependent deacetylase activity and as shown for a few sirtuins, a secondary ADP-ribosyltransferase activity [2] and [3]. To date, seven human and murine sirtuins have been identified (SIRT1–SIRT7), which share a common Sir2 catalytic domain [4], [5], [6] and [7]. This deacetylase domain is being flanked by highly variable N-terminal and C-terminal extensions, suggesting the acquisition of new functions through evolution, which may be required for the regulation of their subcellular localization and/or catalytic activity [7] and [8]. While SIRT1 may be found both, in cell nucleus and in the cytoplasm, SIRT2 has been reported to be exclusively cytoplasmic. SIRT3, SIRT4 and SIRT5 localize to the
mitochondria [9] and [10], while SIRT6 and SIRT7 are solely found in the cell nucleus [11].
