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The gene for a new brain specific RhoA exchange factor maps to the highly unstable chromosomal region 1p36.2–1p36.3.

Oncogene volume 20, pages 7307–7317 (2001)Cite this article

Abstract

Guanine nucleotide exchange factors from the Dbl family are proto-oncogenic proteins that activate small GTPases of the Rho family. Here we report the characterization of GEF720, a novel Dbl-like protein related to p115Rho-GEF. GEF720 activated RhoA both in our recently developed Yeast Exchange Assay and in biochemical in vitro exchange assays. GEF720 induced RhoA dependent assembly of actin stress fibers in REF52 fibroblastic cells. In NIH3T3 cells this Dbl-like protein elicited formation of transformation foci with a morphology similar to RhoA-V14 induced foci. In the PC12 neuron-like cell line, expression of GEF720, whose mRNA is brain specific, inhibited NGF-induced neurite outgrowth. Finally, GEF720 gene is located on human chromosome 1 on band 1p36, between Tumor Protein 73 and Tumor Necrosis Factor Receptor 12, two genes rearranged in many neuroblastoma cell lines. Together, these results show that this new Dbl related protein, GEF720, is an exchange factor that can directly activate RhoA in vivo and is potentially involved in the control of neuronal cell differentiation. GEF720 is also a new candidate gene involved in the progression of neuroblastoma and developmental abnormalities associated with rearrangements in the 1p36 chromosomal region.

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Acknowledgements

The authors want to thank Jacques Camonis and Gérard Zalcman for the gift of pLexRhoC and Pierre Roux for helpful advice for the transformation assays. M De Toledo was supported by a fellowship from the Ministère de l'Education et de la Recherche (France), V Coulon was supported by a fellowship from the Ligue Nationale Contre le Cancer (France), and S Schmidt was supported by a fellowship from the Recherche Suisse Contre le Cancer (Switzerland). This work was mainly supported by grants from the Ligue Nationale Contre le Cancer (Equipe Labellisée) and for a minor part by the Association pour la Recherche contre le Cancer.

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  1. Centre de Recherches en Biochimie Macromoléculaire, CNRS IFR24-UPR 1086, 1919 route de Mende, Montpellier, Cedex 5, 34293, France

    Marion De Toledo, Susanne Schmidt, Philippe Fort & Anne Blangy

  2. Institut de Génétique Moléculaire de Montpellier, CNRS IFR24-UMR 5535, 1919 route de Mende, Montpellier, Cedex 5, 34293, France

    Vincent Coulon

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  1. Marion De Toledo
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Correspondence to Anne Blangy.

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De Toledo, M., Coulon, V., Schmidt, S. et al. The gene for a new brain specific RhoA exchange factor maps to the highly unstable chromosomal region 1p36.2–1p36.3.. Oncogene 20, 7307–7317 (2001). https://doi.org/10.1038/sj.onc.1204921

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