Hsp90 Stabilizes SIRT1 Orthologs in Mammalian Cells and C. elegans.

ABSTRACT: Sirtuin 1 (SIRT1) othologs are ubiquitous NAD⁺-dependent deacetylases that act as nutrient sensors and modulate metabolism and stress responses in diverse organisms. Both mammalian SIRT1 and Caenorhabditis elegans SIR-2.1 have been implicated in dietary restriction, longevity, and healthspan. Hsp90 is an evolutionarily conserved molecular chaperone that stabilizes a plethora of signaling 'client' proteins and regulates fundamental biological processes. Here we report that Hsp90 is required for conformational stabilization of SIRT1 and SIR-2.1. We find that inhibition of Hsp90 by geldanamycin (GA) induces the depletion of mammalian SIRT1 protein in a concentration and time dependent manner in COS-7 and HepG2 cells. In contrast to SIRT1, SIRT2 level remains unchanged by GA treatment,

SUBMITTER: Nguyen MT 

PROVIDER: S-EPMC6274930 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature