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  • Original Paper
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RhoG regulates gene expression and the actin cytoskeleton in lymphocytes

Abstract

RhoG, a member of the Rho family of GTPases, has been implicated as a regulator of the actin cytoskeleton. In this study, we show a novel function for the small GTPase RhoG on the regulation of the interferon-γ promoter and nuclear factor of activated T cells (NFAT) gene transcription in lymphocytes. Optimal function of RhoG for the expression of these genes requires a calcium signal, normally provided by the antigen receptor. In addition, RhoG potentiation of NFAT requires the indirect activity of Rac and Cdc42; however, pathways distinct from those activated by Rac and Cdc42 mediate RhoG activation of NFAT-dependent transcription. Using effector domain mutants of RhoG we found that its ability to potentiate NFAT-dependent transcription correlates with its capacity to increase actin polymerization, supporting the suggestion that NFAT-dependent transcription is an actin-dependent process. RhoG also promotes T-cell spreading on fibronectin, a property that is independent of its ability to enhance NFAT-dependent transcription. Hence, these results implicate RhoG in leukocyte trafficking and the control of gene expression induced in response to antigen encounter.

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Acknowledgements

We thank Nick Kistakis and Maria Manifava for advice and assistance with microscopy, Sue Robinson for secretarial assistance and Babraham Institute Sequencing Support for DNA analysis. This work was funded in part by a Biotechnology and Biological Sciences Research Council Competitive Strategic Grant and by grants from the Leukaemia Research Fund and Cancer Research Campaign (MT).

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Correspondence to Elena Vigorito.

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Vigorito, E., Billadeu, D., Savoy, D. et al. RhoG regulates gene expression and the actin cytoskeleton in lymphocytes. Oncogene 22, 330–342 (2003). https://doi.org/10.1038/sj.onc.1206116

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