RHOA lactylation at oncogenic hotspots promotes oncogenic activity and protein stabilization.

ABSTRACT:

Background

Aberrant RHOA activation drives tumor progression, yet regulatory mechanisms beyond genetic mutations remain poorly defined. Lactylation, a lactate-derived post-translational modification, links metabolic reprogramming to oncogenesis, but its functional mimicry of genetic mutations is unexplored. This study investigates RHOA lactylation at oncogenic hotspots and its role as an "epi-mutation" system.

Methods

RHOA lactylation were identified by pan-lysine lactylation (Kla) antibody-based mass spectrometry. Site-specific lactylation was achieved using an orthogonal Mb-Pyl Kla-RS/Pyl-tRNA pair to incorporate lactyl-lysine at K118/K162 in recombinant RHOA, validated by immunoblotting and fluorescence. Molecular dynamics simulations (AlphaFold 3, BIOVIA DS) analyzed GTP

SUBMITTER: Ma C 

PROVIDER: S-EPMC12750741 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature