RPL23 Links Oncogenic RAS Signaling to p53-Mediated Tumor Suppression.

ABSTRACT: The ribosomal protein (RP)-MDM2 interaction is a p53 response pathway critical for preventing oncogenic c-MYC-induced tumorigenesis. To investigate whether the RP-MDM2-p53 pathway is a broad antioncogenic mechanism, we crossed mice bearing an MDM2(C305F) mutation, which disrupts RPL11 binding to MDM2, with mice expressing an oncogenic Hras(G12V) transgene. Interestingly, the MDM2(C305F)-mutant mice, which are hypersensitive to c-MYC-induced tumorigenesis, are not hypersensitive to oncogenic Hras(G12V)-induced tumorigenesis. Unlike c-MYC, which induces expression of RPL11, RAS overexpression leads to an increase in RPL23 mRNA and protein whereas RPL11 expression remains unchanged. The induction of RPL23 involves both MEK and PI3K signaling pathways and requires mTOR function. Increased expr

SUBMITTER: Meng X 

PROVIDER: S-EPMC5693225 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature