The β-TrCP-Mediated Pathway Cooperates with the Keap1-Mediated Pathway in Nrf2 Degradation In Vivo.

ABSTRACT: Nrf2 activates cytoprotective gene expression, and Nrf2 activity is regulated through at least two protein degradation pathways: the Keap1-mediated and β-TrCP-mediated pathways. To address the relative contributions of these pathways, we generated knock-in mouse lines expressing an Nrf2^SA mutant that harbored two substitution mutations of serine residues interacting with β-TrCP. The homozygous (Nrf2^SA/SA) mice grew normally, with Nrf2 levels comparable to those of wild-type (WT) mice under unstressed conditions. However, when Keap1 activity was suppressed, high levels of Nrf2 accumulated in Nrf2^SA/SA macrophages compared with that in WT macrophages. We crossed Nrf2^SA/SA mice with mice in which Keap1 was knocked down to

SUBMITTER: Kuga A 

PROVIDER: S-EPMC9302178 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature