A Paradoxical Tumor-Suppressor Role for the Rac1 Exchange Factor Vav1 in T Cell Acute Lymphoblastic Leukemia.
[EN]Rho guanine exchange factors (GEFs), the enzymes that stimulate Rho GTPases, are deemed as potential therapeutic targets owing to their protumorigenic functions. However, the understanding of the spectrum of their pathobiological roles in tumors is still very limited. We report here that the GEF...
| Autores: | , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2017 |
| País: | España |
| Institución: | Universidad de Salamanca (USAL) |
| Repositorio: | GREDOS. Repositorio Institucional de la Universidad de Salamanca |
| OAI Identifier: | oai:gredos.usal.es:10366/166944 |
| Acceso en línea: | http://hdl.handle.net/10366/166944 |
| Access Level: | acceso abierto |
| Palabra clave: | Rho guanine exchange factors Rho GTPases T cell acute lymphoblastic leukemia T-Lymphocytes Signal Transduction Proto-Oncogene Proteins c-vav Tumor Suppressor Proteins Precursor T-Cell Lymphoblastic Leukemia-Lymphoma Proto-Oncogene Proteins c-cbl leucemia-linfoma linfoblástico de células T precursoras proteínas supresoras de tumor transducción de señales proteínas protooncogénicas c-vav linfocitos T proteínas protooncogénicas c-cbl |
| Sumario: | [EN]Rho guanine exchange factors (GEFs), the enzymes that stimulate Rho GTPases, are deemed as potential therapeutic targets owing to their protumorigenic functions. However, the understanding of the spectrum of their pathobiological roles in tumors is still very limited. We report here that the GEF Vav1 unexpectedly possesses tumor-suppressor functions in immature T cells. This function entails the noncatalytic nucleation of complexes between the ubiquitin ligase Cbl-b and the intracellular domain of Notch1 (ICN1) that favors ICN1 ubiquitinylation and degradation. Ablation of Vav1 promotes ICN1 signaling and the development of T cell acute lymphoblastic leukemia (T-ALL). The downregulation of Vav1 is essential for the pathogenesis of human T-ALL of the TLX+ clinical subtype, further underscoring the suppressor role of this pathway. |
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