Mapping the Interactome of KRAS and Its G12C/D/V Mutants by Integrating TurboID Proximity Labeling with Quantitative Proteomics.

ABSTRACT: KRAS mutations are major drivers of human cancers, yet how distinct mutations rewire protein interactions and metabolic pathways to promote tumorigenesis remains poorly understood. To address this, we systematically mapped the protein interaction networks of wild-type KRAS and three high-frequency oncogenic mutants (G12C, G12D, and G12V) using TurboID proximity labeling coupled with quantitative proteomics. Bioinformatic analysis revealed mutant-specific binding partners and metabolic pathway alterations, including significant enrichment in insulin signaling, reactive oxygen species regulation, and glucose/lipid metabolism. These changes collectively drive tumor proliferation and immune evasion. Comparative analysis identified shared interactome shifts across all mutants: reduced binding t

SUBMITTER: Song J 

PROVIDER: S-EPMC12109396 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature