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  • Original Paper
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Oncogenic transformation by ras and fos is mediated by c-Jun N-terminal phosphorylation

Abstract

The nuclear phosphoprotein c-Jun is a major component of the AP-1 transcription factor, whose activity is augmented by many oncogenes. An important mechanism to stimulate AP-1 function is N-terminal phosphorylation of c-Jun at the serine residues 63 and 73 by the c-JunN-terminal kinases (JNKs). Mice and cells harboring a mutant allele of c-jun, which has the JNK phosphoacceptor serines changed to alanines (junAA), were used to determine the function of c-Jun N-terminal phosphorylation (JNP) during oncogenic transformation in vitro and in vivo. JunAA immortalized fibroblasts expressing v-ras and v-fos showed reduced tumorigenicity in nude mice, but the efficiency of v-src transformation was unaffected by the lack of JNP. To assess the significance of JNP in tumour development in vivo, two transgenic mouse tumour models were employed. Skin tumour development caused by constitutive activation of the ras pathway by K5-SOS-F expression and c-fos-induced osteosarcoma formation were impaired in mice lacking JNP. Inhibition of JNP may, therefore, be a novel therapeutic strategy to inhibit tumour growth in vivo.

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Acknowledgements

We thank Svetlana Pekez for maintaining the mouse colony. We are also grateful to Uta Moehle-Steinlein for technical assistance, to Moshe Yaniv for antibodies, to Gerhard Christofori, Thomas Jenuwein and Laura Stingl for critical reading of the manuscript and to Hannes Tkadletz for help with preparing the illustrations. Supported in part by the Austrian Federal Ministry of Science, Transport and the Arts and the Austrian Industrial Research Promotion Fund.

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Behrens, A., Jochum, W., Sibilia, M. et al. Oncogenic transformation by ras and fos is mediated by c-Jun N-terminal phosphorylation. Oncogene 19, 2657–2663 (2000). https://doi.org/10.1038/sj.onc.1203603

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