Suppression of E1A-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-erbB2/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 formation by NIH 3T3 cells and transformation of primary rat embryo fibroblasts but had no observed effect in the absence of E1A. Domains in p50E4F required for stimulation of the adenovirus E4 promoter were required for the suppressive effect, indicating a transcriptional mechanism. In serum-containing media, retroviral expression of p50E4F in E1A13S/ras-transformed NIH 3T3 fibroblasts had little effect on subconfluent cultures but accelerated a decline in viability after the cultures reached confluence. Cell death occurred by both apoptosis and necrosis, with the predominance of each process determined by culture conditions. In serum-free media, p50E4F accelerated E1A-induced apoptosis. The results suggest that p50E4F sensitizes cells to signals or conditions that cause cell death.
Fernandes
E R
ER
Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Rooney
R J
RJ
D016475:3T3 Cells; D017500:Adenovirus E1A Proteins / Q000235:genetics* / Q000378:metabolism; D017504:Adenovirus E4 Proteins / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D001665:Binding Sites; D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology; D015967:Gene Expression Regulation, Viral; D006801:Humans; D051379:Mice; D051381:Rats; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D018631:ras Proteins / Q000235:genetics*
D017500:Adenovirus E1A Proteins; D017504:Adenovirus E4 Proteins; D004268:DNA-Binding Proteins; D014157:Transcription Factors; C112060:p50E4F protein, rat; D018631:ras Proteins