Oncogenic non-V600 mutations evade the regulatory machinery of RAF including the Cdc37/Hsp90 chaperone and the 14-3-3 scaffold.

ABSTRACT: The Ser/Thr kinase RAF, particularly BRAF isoform is a dominant target of oncogenic mutations and many mutations have been identified in various cancers. However, how these mutations except V600E evade the regulatory machinery of RAF protein and hence trigger its oncogenicity remains unclear. Methods: In this study, we used mutagenesis, peptide affinity assay, immunoprecipitation, immunoblot, and complementary split luciferase assay as well as mouse xenograft tumour model to investigate how the function of RAF is cooperatively regulated by Cdc37/Hsp90 chaperones and 14-3-3 scaffolds and how this regulatory machinery is evaded by prevalent non-V600 mutations. Results: We found that Cdc37/Hsp90 chaperones engaged with mature BRAF proteins promoted together with 14-3-3 scaffolds

SUBMITTER: Wan X 

PROVIDER: S-EPMC11780520 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature