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 reg ulation of apoptosis during neoplastic progression [sup(+)I (stage I) and s up(-)II (stage II)]. Sup(+)I cells are prone to undergo apoptosis, while su p(-)II cells are relatively resistant. We report that induction of apoptosi s in sup(+)I cells is tightly correlated with the formation of c-Fos/p300 c omplexes, 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 ov er-expression of c-Fos, concomitant c-Fos:p300 complexes were detected. Ove rexpression of p300 resulted in apoptosis in sup(-)II cells and also in p53 (wt) human tumor cells, but not in p53(mutant) human tumor cells. Over-expr ession of the C-terminal fragment of p300, which contains the c-fos binding site, enhanced apoptosis, suggesting that the c-fos:p300 complex is active ly involved in apoptosis. We propose that p300 could function as a general mediator of transcription factor-induced apoptosis.