As first shown for SIRT2 (99–101), a cytoplasmically localized protein, sirtuins have a deacetylation activity requiring NAD+, but not as an electron carrier. Instead, their reactions use NAD+ in equal stoichiometry to the acetyl group and cleave NAD, generating nicotinamide and 2′-O-acetyl-ADP-ribose. Of the seven mammalian sirtuins, SIRT1, SIRT 6, and SIRT 7 are nuclear proteins, enriched in the nucleoplasm, in heterochromatin, and in nucleoli, respectively, and positioned to deacetylate histones and other nuclear proteins (102). SIRT1 efficiently deacetylates p53 (102).
