Analysis of AP-1 function in cellular transformation pathways.

摘要: To understand the role of endogenous AP-1 activity in cellular transformation induced by oncogenes, we have made use a fos mutant (supfos-1) and jun (supjun-1), either which can function as transdominant inhibitor AP-1-mediated transcriptional regulation. Chicken embryo fibroblasts (CEF) infected with series transforming retroviruses were doubly retrovirus carrying supfos-1 or supjun-1, suppression was monitored terms reversion to normal morphology acquisition anchorage-dependent growth. Cellular several exogenously expressed genes family efficiently suppressed, expected. CEF transformed v-src, v-yes, v-fps, c-Ha-ras, N-terminally truncated c-raf also revert phenotype these mutants, suggesting that functional transcription factor is essential for oncogenes. The not attributable nonspecific inhibition proliferation, because v-ros v-myc phenotype. We next analyzed changes all known components chicken activated transformation. levels both Fra-2 c-Jun expression elevated two- fourfold, hyperphosphorylation observed. further showed Fra-2-c-Jun heterodimer mainly responsible DNA-binding cells, propose this play crucial