P62 Promotes Survival and Hepatocarcinogenesis in Mice with Liver-Specific NEMO Ablation.

ABSTRACT: SQSTM1/p62 is a multitasking protein that functions as an autophagy receptor, but also as a signaling hub regulating diverse cellular pathways. p62 accumulation in mice with autophagy-deficient hepatocytes mediates liver damage and hepatocarcinogenesis through Nrf2 overactivation, yet the role of the p62-Keap1-Nrf2 axis in cell death and hepatocarcinogenesis in the absence of underlying autophagy defects is less clear. Here, we addressed the role of p62 and Nrf2 activation in a chronic liver disease model, namely mice with liver parenchymal cell-specific knockout of NEMO (NEMO^LPC-KO), in which we demonstrate that they show no inherent autophagy impairment. Unexpectedly, systemic p62 ablation aggravated the phenotype and caused early postnatal lethality in NEMO^LPC-KO m

SUBMITTER: Kondylis V 

PROVIDER: S-EPMC9139637 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature