Abstract
v-Rel is the acutely oncogenic member of the NF-κB family of transcription factors. Infection with retroviruses expressing v-Rel rapidly induces fatal lymphomas in birds and transforms primary lymphocytes and fibroblasts in vitro. We have previously shown that AP-1 transcriptional activity contributes to v-Rel-mediated transformation. Although v-Rel increases the expression of these factors, their activity may also be induced through phosphorylation by the mitogen-activated protein kinases (MAPKs). The expression of v-Rel results in the strong and sustained activation of the ERK and JNK MAPK pathways. This induction is critical for the v-Rel-transformed phenotype, as suppression of MAPK activity with chemical inhibitors or small interfering RNA severely impairs colony formation of v-Rel-transformed lymphoid cell lines. However, signaling must be maintained within an optimal range in these cells, as strong additional activation of either pathway beyond the levels induced by v-Rel through the expression of constitutively active MAPK proteins attenuates the transformed phenotype. MAPK signaling also has an important role in the initial transformation of primary spleen cells by v-Rel, although distinct requirements for MAPK activity at different stages of v-Rel-mediated transformation were identified. We also show that the ability of v-Rel to induce MAPK signaling more strongly than c-Rel contributes to its greater oncogenicity.
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Acknowledgements
We thank the laboratories of Natalie Ahn and Aming Lin for generously providing the CA MKK constructs. This work was supported by Public Health Service grants CA33192 and CA098151 from the National Cancer Institute. Jarmila Kralova was supported, in part, by grant KAN200200651 from the Grant Agency of the Academy of Sciences of the Czech Republic. We also thank R Hrdlicková and J Nehyba for their critical reading of the manuscript.
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Kralova, J., Sheely, J., Liss, A. et al. ERK and JNK activation is essential for oncogenic transformation by v-Rel. Oncogene 29, 6267–6279 (2010). https://doi.org/10.1038/onc.2010.359
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DOI: https://doi.org/10.1038/onc.2010.359
