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J. Biol. Chem., Vol. 269, Issue 28, 18434-18440, Jul, 1994
A Morosov, WC Phelps and P Raychaudhuri
The E6 and the E7 genes of the high-risk types of human papillomavirus
(types 16 and 18) are associated with the induction or maintenance of
malignant growth. The molecular mechanism by which these oncogenes
contribute to the malignant phenotype is not clear. To study the effects of
E7 on cellular processes, we constructed a stable cell line that inducibly
expressed the E7 gene of HPV16. By using this cell line, we provide
evidence that expression of E7 of HPV16 stimulates c-fos gene expression.
Also, by doing transient transfection experiments, we show that the
expression of either E6 or E7 induces transcription from the c-fos
promoter. Analysis of a series of c-fos promoter mutants indicates that the
activation by both E6 and E7 is dependent on the cyclic AMP response
element. To further investigate the mechanism(s) of the activation of the
c-fos gene and their relation to the oncogenic properties of E6 and E7,
several mutants of the E6 and E7 genes were analyzed. The results of these
studies indicate that the CR1 and CR2 regions in the E7 protein, and
sequences distinct from the p53-binding region in the E6 protein, are
critical for activation of the c-fos promoter.
Activation of the c-fos gene by the HPV16 oncoproteins depends upon the cAMP-response element at -60
Department of Biochemistry, University of Illinois, Chicago 60612.
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