Mice Deficient in the RNA-Binding Protein Zfp871 Are Prone to Early Death and Steatohepatitis in Part through the p53-Mdm2 Axis.

ABSTRACT: p53 transcription factor is activated upon exposure to various cellular stresses, leading to growth suppression. However, aberrant activation of p53 can lead to defects in embryonic development and other abnormalities. Here, we identified zinc finger protein Zfp871 as a p53 target gene. We showed that as an RNA-binding protein, Zfp871 binds to Mdm2 3'UTR and stabilizes Mdm2 mRNA, which in turn suppresses p53 expression through increased expression of Mdm2 E3 ubiquitin ligase. Consistently, Zfp871 deficiency increases p53 expression, leading to growth suppression in a p53-dependent manner. To determine the role of Zfp871 in the p53 pathway, we used Zfp871-deficient mouse model and found that Zfp871-null mice were prone to embryonic/pre-weaning lethality, which can be partially

SUBMITTER: Mohibi S 

PROVIDER: S-EPMC8492495 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature