NRF2 Activation in Autophagy Defects Suppresses a Pharmacological Transactivation of the Nuclear Receptor FXR.

ABSTRACT: NF-E2-related factor 2 (NRF2), an antioxidant transcription factor, is activated in autophagy-deficient mice due to the accumulations of p62/SQSTM1 and its subsequent interaction with Kelch-like-ECH-associated protein 1 (KEAP1), an adaptor component for Cullin3-based E3 ubiquitin ligase complex. Farnesoid x receptor (FXR/NR1H4) is a ligand-dependent transcription factor that belongs to the nuclear receptor superfamily. FXR plays an essential role in bile acid synthesis and enterohepatic circulation, affecting glucose and lipid metabolism. Obeticholic acid as a potent FXR agonist has been approved to treat primary biliary cholangitis and clinical trials for its use in the treatment of other liver diseases are underway. Here we show that NRF2 activation in autophagy defects impedes a transac

SUBMITTER: Kim EY 

PROVIDER: S-EPMC8868494 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature