New insights into the classification of the RAC1 P29S hotspot mutation in melanoma as an oncogene.

ABSTRACT: The RAC1^P29S hotspot mutation, which is prevalent in melanoma, drives tumorigenesis by promoting the persistent activation of RAC1. This mutation enhances molecular interactions, and hyperactivates key signaling pathways, making RAC1^P29S a promising target for cancer therapy. This study provides a comprehensive biochemical and cell-based characterization of RAC1^P29S, as well as comparisons with wild-type RAC1 and the T17N and F28L mutants. The P29S substitution significantly impairs nucleotide binding while accelerating intrinsic nucleotide exchange. While it minimally affects regulation by guanosine dissociation inhibitor 1 (GDI1), RAC1^P29S exhibits reduced activation via DBL family guanine nucleotide exchange factors (GEFs) but retains effectiv

SUBMITTER: Mirzaiebadizi A 

PROVIDER: S-EPMC12702776 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature