The mammalian sirtuin (SIRT) family, evolutionally conserved proteins belonging to class III histone deacetylases (HDACs), comprises seven members. SIRTs share a NAD+-binding catalytic domain and may act specifically on different substrates depending on the biological processes in which they are involved. SIRTs differ in sequence and length in both their N- and C-terminal domains, partially explaining their different localization and functions. SIRTs can catalyze both deacetylation and ADP-ribosylation. 
SIRT1 regulates many tumor suppressors and DNA repair genes. SIRT1 upregulation is described in many human malignancies. SIRT2 is involved in apoptosis control through p53 process regulation. Several studies confirm the role of SIRT2 in the control of cell cycle progression at many levels. It was demonstrated that it is a checkpoint for metaphase/anaphase processes and G2/M transition. SIRT2 is capable to deacetylate the Glucokinase (GCK), an essential enzyme for maintaining homeostasis of glucose regulated by the binding of the glucokinase regulatory protein (GKRP). Acetylated GKRP is connected to diabetes mellitus.  
SIRT3 acts as a tumor suppressor by inhibiting glycolysis metabolism after the deacetylation and activation of pyruvate dehydrogenase; thus, also the role of SIRT3 in cancer is debatable. SIRT4 inhibits proliferation, invasion, and migration in colorectal cancer cells, and its low expression is correlated with a worse prognosis. SIRT5 is reported to interact with carbamoyl phosphate synthetase 1 (CPS1), and it is deacetylated by SIRT5. SIRT6 was reported to display actions controlling cellular homeostasis, DNA repair, telomere maintenance, and metabolism, acting as an epigenetic guardian for cellular differentiation. SIRT7 catalyzes selective deacetylation of H3K18, an emerging epigenetic biomarker of aggressive tumors, controlling many tumor suppressor genes.


1.Carafa V, et al. Clin Epigenetics. 2016;8:61.