Apoptotic response to growth factor deprivation involves cooperative interactions between c-Fos and p300

Two preneoplastic cell lines have been utilized to study changes in the regulation of apoptosis during neoplastic progression [sup+I (stage I) and sup-II (stage II)]. Sup+I cells are prone to undergo apoptosis, while sup-II cells are relatively resistant. We report that induction of apoptosis in sup+I cells is tightly correlated with the formation of c-Fos/p300 complexes, which were not present in the non-apoptotic sup-II cells under the same conditions. When apoptosis was induced in the sup-II cells by over-expression of c-Fos, concomitant c-Fos:p300 complexes were detected. Over-expression of p300 resulted in apoptosis in sup-II cells and also in p53wt human tumor cells, but not in p53mutant human tumor cells. Over-expression of the C-terminal fragment of p300, which contains the c-Fos binding site, enhanced apoptosis, suggesting that the c-Fos:p300 complex is actively involved in apoptosis. We propose that p300 could function as a general mediator of transcription factor-induced apoptosis.