Phosphorylation-Induced Ubiquitination and Degradation of PXR through CDK2-TRIM21 Axis.

ABSTRACT: Pregnane X receptor (PXR) is a member of the nuclear receptor superfamily that is activated by a variety of endogenous metabolites or xenobiotics. Its downstream target genes are involved in metabolism, inflammation and processes closely related to cancer. However, the stability regulation of PXR protein resulting from post-translational modification is still largely undefined. In the present study, primary mouse hepatocytes, hepatoma HepG2 cells and HEK 293T cells were used to investigate gene expression and protein interactions. The role of kinases was evaluated by RNA interference and overexpression constructs with or without PXR phosphorylation site mutations. The activity of CYP3A4 and P-gp was determined by enzymatic and substrate accumulation assays. It was found that E3 ubiquitin l

SUBMITTER: Qin M 

PROVIDER: S-EPMC8773821 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature