Terry Riss1, Nathan Evans1, Michael A. Scurria2, Tim Ugo2, Caesar Corona2, Thomas Kirkland2 and Andrew Niles1
1Promega Corporation, 2800 Woods Hollow Road, Madison, WI 53711
2Promega Biosciences LLC, 277 Granada Dr., San Luis Obispo, CA 93401
The NAD+ dependent, Class III histone deacetylases, also know as Sirtuins (SIRTs), play key roles in gene regulation by modifying the acetylation status of core histone tails as well as non-histone regulatory proteins in the cytosol and mitochondria. Modulation of SIRT activities holds promise from a therapeutic perspective to address metabolic disorders and disease associated with the aging process. Unfortunately, the biological relationships between specific SIRTs and disease are poorly characterized and more effective tools are sought for discovery of biologically relevant inhibitors or activators. Here we describe a homogeneous, single addition, bioluminogenic assay for SIRT activities that leverages the sensitivity, scalability and robustness of luminescence for screening environments. We will describe the assay's utility with a variety of SIRT inhibitors of varying structure and a putative SIRT activator.