SIRT1 enzymatically potentiates 1,25-dihydroxyvitamin D₃ signaling via vitamin D receptor deacetylation.

ABSTRACT: The hormonal metabolite of vitamin D, 1,25-dihydroxyvitamin D₃ (1,25D), binds to the vitamin D receptor (VDR) and promotes heterodimerization of VDR with a retinoid-X-receptor (RXR) to genomically regulate diverse cellular processes. Herein, it is revealed for the first time that VDR is post-translationally acetylated, and that VDR immunoprecipitated from human embryonic kidney (HEK293) cells displays a dramatic decrease in acetylated receptor in the presence of 1,25D-ligand, sirtuin-1 (SIRT1) deacetylase, or the resveratrol activator of SIRT1. To elucidate the functional significance of VDR deacetylation, vitamin-d-responsive-element (VDRE)-based transcriptional assays were performed to determine if deacetylase overexpression affects VDR/VDRE-driven transcription. In HEK293 kid

SUBMITTER: Sabir MS 

PROVIDER: S-EPMC5584940 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature