The RAS-interacting chaperone UNC119 drives the RASSF6-MDM2-p53 axis and antagonizes RAS-mediated malignant transformation.

ABSTRACT: The gene encoding the proto-oncogene GTPase RAS is frequently mutated in human cancers. Mutated RAS proteins trigger antiapoptotic and cell-proliferative signals and lead to oncogenesis. However, RAS also induces apoptosis and senescence, which may contribute to the eradication of cells with RAS mutations. We previously reported that Ras association domain family member 6 (RASSF6) binds MDM2 and stabilizes the tumor suppressor p53 and that the active form of KRAS promotes the interaction between RASSF6 and MDM2. We also reported that Unc-119 lipid-binding chaperone (UNC119A), a chaperone of myristoylated proteins, interacts with RASSF6 and regulates RASSF6-mediated apoptosis. In this study, using several human cancer cell lines, quantitative RT-PCR, RNAi-based gene silencing, and immunopre

SUBMITTER: Shimizu T 

PROVIDER: S-EPMC7415979 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature