Article
SMURF2 Facilitates GAP17 Isoform 1 Membrane Displacement to Promote Mutant p53-KRAS Oncogenic Synergy.
Molecular cancer research : MCR - 3 Jun 2025
Ray Paramita, Shukla Shirish, Zhang Yaqing, Donahue Katelyn L, Nancarrow Derek J, Kasturirangan Srimathi, Shankar Sunita, Cuneo Kyle, Thomas Dafydd, Gadgeel Shirish M, Lawrence Theodore S, Pasca di Magliano Marina, Ray Dipankar
Abstract excerpt
Cooperativity between mutant p53 and mutant KRAS, although recognized, is poorly understood. In pancreatic cancer, mutant p53 induces splicing factor hnRNPK, causing an isoform switch that produces overexpression of GTPase-activating protein 17 isoform 1 (GAP17-1). GAP17-1 is mislocalized in the cytosol instead of the membrane, owing to the insertion of exon 17 encoding a PPLP motif, thus allowing mutant KRAS to...
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