Suppression of E11A-mediated transformation by the p50E4F transcription factor

The adenovirus E1A gene can act as an oncogene or a tumor suppressor, with the latter effect generally arising from the induction of apoptosis or the repression of genes that provide oncogenic growth stimuli (e.g., HER-2/c-er bB2/neu) or increased metastatic invasiveness (e.g., metalloproteases). In this study, coexpression of E1A and p50E4F, a cellular transcription factor whose DNA binding activity is stimulated by E1A, suppressed colony formati on by NIH 3T3 cells and transformation of primary rat embryo fibroblasts bu t had no observed effect in the absence of E1A. Domains in p50E4F required for stimulation of the adenovirus E4 promoter were required for the suppres sive effect, indicating a transcriptional mechanism. In serum-containing me dia, retroviral expression of p50E4F in E1A13S/ras-transformed NIH 3T3 fibr oblasts had little effect on subconfluent cultures but accelerated a declin e in viability after the cultures reached confluence. Cell death occurred b y both apoptosis and necrosis, with the predominance of each process determ ined by culture conditions. In serum-free media, p50E4F accelerated E1A ind uced apoptosis. The results suggest that p50E4F sensitizes cells to signals or conditions that cause cell death.