EIF1AX and RAS Mutations Cooperate to Drive Thyroid Tumorigenesis through ATF4 and c-MYC.

ABSTRACT: Translation initiation is orchestrated by the cap binding and 43S preinitiation complexes (PIC). Eukaryotic initiation factor 1A (EIF1A) is essential for recruitment of the ternary complex and for assembling the 43S PIC. Recurrent EIF1AX mutations in papillary thyroid cancers are mutually exclusive with other drivers, including RAS. EIF1AX mutations are enriched in advanced thyroid cancers, where they display a striking co-occurrence with RAS, which cooperates to induce tumorigenesis in mice and isogenic cell lines. The C-terminal EIF1AX-A113splice mutation is the most prevalent in advanced thyroid cancer. EIF1AX-A113splice variants stabilize the PIC and induce ATF4, a sensor of cellular stress, which is co-opted to suppress EIF2α phosphorylation, enablin

SUBMITTER: Krishnamoorthy GP 

PROVIDER: S-EPMC6373451 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature