Cancer-associated MDM2 W329G mutant attenuates ribosomal stress-mediated p53 responses to promote cell survival and glycolysis.

ABSTRACT: Although amplification/overexpression is the predominant mechanism for the oncogenic properties of MDM2, an increasing number of MDM2 somatic missense mutations were identified in cancer patients with the recent advances in sequencing technology. Here, we characterized an MDM2 cancer-associated mutant variant W329G identified from a patient sample that contains a wild-type p53 gene. Trp329 is one of residues that were reported to be critical to MDM2's binding to ribosomal protein L11 (RPL11). We found that the MDM2 W329G mutant was resistant to the inhibitory effect of RPL11 on MDM2-mediated p53 ubiquitination and degradation, in line with its defect on RPL11 binding. Using isogenic U2OS cells with or without endogenous MDM2 W329G mutation, we demonstrated that the expression of classic p5

SUBMITTER: Lien S 

PROVIDER: S-EPMC11162693 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature