title: 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. Oncogene (2000).
authors.affiliation: Research Institute of Molecular Pathology (IMP), Dr. Bohr-Gasse 7, A-1030 Vienna, Austria.
authors.forename: A
authors.initials: A
authors.lastname: Behrens
authors.forename: W
authors.initials: W
authors.lastname: Jochum
authors.forename: M
authors.initials: M
authors.lastname: Sibilia
authors.forename: E F
authors.initials: EF
authors.lastname: Wagner
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D016762:Genes, fos; D011905:Genes, ras; D048031:JNK Mitogen-Activated Protein Kinases; D051379:Mice; D008819:Mice, Nude; D008822:Mice, Transgenic; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics*; D009374:Neoplasms, Experimental / Q000235:genetics* / Q000473:pathology; D010766:Phosphorylation; D015398:Signal Transduction / Q000235:genetics
chemical_list: D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases