Vav1 mutations: What makes them oncogenic?

Marganit Farago, Tali Yarnitzky, Batel Shalom, Shulamit Katzav

Cellular signalling 2020 Jan

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Vav1 is physiologically active as a GDP/GTP nucleotide exchange factor (GEF) in the hematopoietic system. Its wild-type form was recently implicated in mammalian malignancies of hematologic and non-hematologic tissue origins. Moreover, it was recently identified as a mutated gene in human cancers of various origins. In this review we focus on the functional activities of several of the Vav1 mutants analyzed for their tumorigenic properties. We also discuss the relationship of the tested biochemical properties of Vav1 mutants, E59K, D517E and L801P, to their computer-based predicted properties. These comparisons further enhance the need for integration of computation-based structural analyses with experimental data in order to fully appreciate the activity of mutant proteins. Our comprehensive evaluation supports the classification of Vav1 as a bona fide oncogene in human cancers. Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.