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Molecular and Cellular Biology, September 1998, p. 5032-5041, Vol. 18, No. 9
Department of Pathology, Harvard Medical
School, Boston, Massachusetts 02115,1 and
Department of Molecular and Cell Biology, University of
California Berkeley, Berkeley, California 947202
Received 18 March 1998/Returned for modification 3 June
1998/Accepted 12 June 1998
The adenovirus E1A protein both activates and represses gene
expression to promote cellular proliferation and inhibit
differentiation. Here we report the identification and characterization
of a cellular protein that antagonizes transcriptional activation and
cellular transformation by E1A. This protein, termed CREG for
cellular repressor of E1A-stimulated genes, shares limited sequence
similarity with E1A and binds both the general transcription
factor TBP and the tumor suppressor pRb in vitro. In transfection
assays, CREG represses transcription and antagonizes 12SE1A-mediated
activation of both the adenovirus E2 and cellular hsp70 promoters.
CREG also antagonizes E1A-mediated transformation, as expression of
CREG reduces the efficiency with which E1A and the oncogene
ras cooperate to transform primary cells. Binding sites for
E2F, a key transcriptional regulator of cell cycle progression,
were found to be required for repression of the adenovirus E2
promoter by CREG, and CREG was shown to inhibit activation by E2F.
Since both the adenovirus E1A protein and transcriptional activation by
E2F function to promote cellular proliferation, the results presented
here suggest that CREG activity may contribute to the transcriptional
control of cell growth and differentiation.
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
A Cellular Repressor of E1A-Stimulated Genes
That Inhibits Activation by E2F
*
Corresponding author. Mailing address: Department of
Pathology, Harvard Medical School, 200 Longwood Ave., Boston, MA 02115. Phone: (617) 432-0985. Fax: (617) 432-1313. E-mail:
ggill{at}warren.med.harvard.edu.
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