Sirtuin family protein (SIRT)

Sirtuin family proteins are a highly conserved group of enzymes that function primarily as NAD+-dependent lysine deacylases and/or mono ADP-ribosyltransferases. They regulate a wide range of biological processes including epigenetic gene silencing through histone modification; DNA repair; cellular metabolism; oxidative stress response; apoptosis; cell cycle progression; and organismal aging/longevity. The founding member was discovered in yeast (Sir2), with mammalian homologs named SIRTs followed by numbers indicating specific isoforms (e.g., SIRT1–7). Each member has distinct subcellular localization—nuclear (e.g., SIRT1, SIRT6, SIRT7), cytoplasmic (e.g., SIRT2), mitochondrial (e.g., SIRTs3–5)—and unique substrate specificity/functionality. Their dysregulation is implicated in diverse diseases including cancer progression/metastasis, neurodegeneration, cardiovascular dysfunction, metabolic syndrome, and age-related pathologies.

Other names

Sir2 proteinSilent information regulator 2NAD-dependent deacetylaseMono-ADP-ribosyltransferaseSirtuins

Drugs targeting sirtuins generally act by modulating their enzymatic activity. Mechanisms include: - Activation of NAD+-dependent deacetylation or ADP-ribosylation activity to promote beneficial effects on metabolism and aging. - Inhibition of sirtuin activity to alter cell survival pathways in cancer or other diseases.