Development of a NanoBRET assay to validate inhibitors of Sirt2-mediated lysine deacetylation and defatty-acylation that block prostate cancer cell migration
Anja Vogelmann, Matthias Schiedel, Nathalie Wössner, Annika Merz, Daniel Herp, Sören Hammelmann, Arianna Colcerasa, Garrison Komaniecki, JY. Hong, Manuela Sum, Eric Metzger, Emilia Neuwirt, L. Zhang, Oliver Einsle, Olaf Groß, Roland Schüle, Hening Lin, Wolfgang Sippl, Manfred Jung
Abstract
and in cells. We show that simultaneous inhibition of both Sirt2 activities results in strongly reduced levels of the oncoprotein c-Myc and an inhibition of cancer cell migration. Furthermore, we describe the development of a NanoBRET-based assay for Sirt2, thereby providing a method to study cellular target engagement for Sirt2 in a straightforward and accurately quantifiable manner. Applying this assay, we could confirm cellular Sirt2 binding of our new Sirt2 inhibitors and correlate their anticancer effects with their cellular target engagement.