<i>In vivo</i> validation of the palmitoylation cycle as a therapeutic target in <i>NRAS</i>-mutant cancer.

ABSTRACT: Normal and oncogenic Ras proteins are functionally dependent on one or more lipid modifications^1,2. Whereas K-Ras4b farnesylation is sufficient for stable association with the plasma membrane, farnesylated H-Ras, K-Ras4a, and N-Ras traffic to the Golgi where they must undergo palmitoylation before regulated translocation to cell membranes. N-Ras palmitoylation by the DHHC family of palmitoyl acyl transferases (PATs) and depalmitoylation by ABHD17 serine hydrolases is a dynamic process that is essential for the growth of acute myeloid leukemias (AMLs) harboring oncogenic NRAS mutations^3-6. Here, we have tested whether co-targeting ABHD17 enzymes and Ras signal output would cooperatively inhibit the proliferation and survival of NRAS-mutant AMLs while spar

SUBMITTER: Decker M 

PROVIDER: S-EPMC11957127 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature