Cancer-associated mutations in VAV1 trigger variegated signaling outputs and T-cell lymphomagenesis.

ABSTRACT: Mutations in VAV1, a gene that encodes a multifunctional protein important for lymphocytes, are found at different frequencies in peripheral T-cell lymphoma (PTCL), non-small cell lung cancer, and other tumors. However, their pathobiological significance remains unsettled. After cataloguing 51 cancer-associated VAV1 mutations, we show here that they can be classified in five subtypes according to functional impact on the three main VAV1 signaling branches, GEF-dependent activation of RAC1, GEF-independent adaptor-like, and tumor suppressor functions. These mutations target new and previously established regulatory layers of the protein, leading to quantitative and qualitative changes in VAV1 signaling output. We also demonstrate that the most frequent VAV1 mutant subtype drives PTCL format

SUBMITTER: Robles-Valero J 

PROVIDER: S-EPMC8591544 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature