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Molecular and Cellular Biology, July 1999, p. 4739-4749, Vol. 19, No. 7
Department of Biochemistry, St. Jude
Children's Research Hospital, Memphis, Tennessee
38105,1 and Department of Genetics, Duke
University Medical Center, Durham, North Carolina
277102
Received 25 January 1999/Returned for modification 24 February
1999/Accepted 20 April 1999
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.
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Suppression of E1A-Mediated Transformation by the
p50E4F Transcription Factor
and
*
Corresponding author. Mailing address: Department of
Genetics, Duke University Medical Center, P. O. Box 3054, Durham,
NC 27710. Phone: (919) 684-4262. Fax: (919) 684-2790. E-mail:
robert.rooney{at}duke.edu.
Present address: Curagen Corp., New Haven, CT 06555.
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