Regulation of hepatic circadian metabolism by the E3 ubiquitin ligase HRD1-controlled CREBH/PPARα transcriptional program.

ABSTRACT:

Objective

The endoplasmic reticulum (ER)-resident E3 ligase HRD1 and its co-activator Sel1L are major components of ER-associated degradation (ERAD) machinery. Here, we investigated the molecular mechanism and functional significance underlying the circadian regulation of HRD1/Sel1L-mediated protein degradation program in hepatic energy metabolism.

Methods

Genetically engineered animal models as well as gain- and loss-of-function studies were employed to address the circadian regulatory mechanism and functional significance. Gene expression, transcriptional activation, protein-protein interaction, and animal metabolic phenotyping analyses were performed to dissect the molecular network and metabolic pathways.

Results

Hepatic HRD1 and Sel1L expression exhibits circadia

SUBMITTER: Kim H 

PROVIDER: S-EPMC7966871 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature