The v-Jun oncoprotein replaces p39 c-Jun as the predominant AP-1 constituent in ASV17-transformed fibroblasts: implications for SAPK/JNK-mediated signal transduction.
We have investigated the expression of Jun family proteins and composition of AP-1 in chicken embryo fibroblasts before and after transformation by the v-Jun oncoprotein of ASV17. We show that p39 c-Jun is the predominant Jun family protein expressed in normal fibroblasts, and that heterodimers of c-Jun and Fos-related partners (Fra's) account for the majority of the AP-1 DNA binding activity. Unexpectedly, because ASV17-transformed fibroblasts do not express p39 c-Jun, v-Jun replaces c-Jun as the predominant AP-1 constituent in association with similar or identical Fra's. This substitution has little effect on the overall level of TRE-specific DNA binding activity, however it results in a profound reduction in TRE-dependent transcriptional activity and a striking defect in signal-regulated phosphorylation of the Jun component of AP-1; whilst agonists of SAPK/JNK kinases trigger transient N-terminal phosphorylation of c-Jun in normal fibroblasts, no corresponding modification of v-Jun occurs in ASV17-transformed cells. Because SAPK/JNK-mediated phosphorylation is thought to regulate c-Jun transcriptional activity and thereby cellular gene expression in response to extracellular signals, we propose that subversion of this signal transduction process by v-Jun is likely to contribute to oncogenesis by ASV17.
Kilbey
A
A
Beatson Institute for Cancer Research, Cancer Research Campaign Beatson Laboratories, glascow, UK.
Black
E J
EJ
Unlu
M
M
Gillespie
D A
DA
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000502:physiology*; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D002642:Chick Embryo; D015500:Chloramphenicol O-Acetyltransferase / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases; D051379:Mice; D020928:Mitogen-Activated Protein Kinases; D008969:Molecular Sequence Data; D016759:Oncogene Protein p65(gag-jun) / Q000378:metabolism*; D010766:Phosphorylation; D016755:Proto-Oncogene Proteins c-jun / Q000032:analysis / Q000378:metabolism*; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000737:chemistry / Q000378:metabolism*
D016759:Oncogene Protein p65(gag-jun); D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; D004247:DNA; D015500:Chloramphenicol O-Acetyltransferase; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases