Wild-type human p53 activates the human epidermal growth factor receptor promoter.
We show that wild-type human p53 transactivates the human epidermal growth factor receptor (EGFR) promoter in vivo in a dose-dependent manner, implicating p53 in promotion of cell proliferation. This activation is sensitive to the expression of cellular oncoprotein MDM2 and human papillomavirus type 18 (HPV-18) E6 protein. The p53 response element is localized within -15 and -569 of the promoter. The EGFR promoter does not have a TATA box, and has low activity in Saos-2 cells in the absence of p53. Results from our in vivo transient transfection assays suggest that p53-binding sites, without any other known promoter element, can act as bidirectional promoters in the presence of wild-type p53. Gel retardation analyses suggest that p53 may serve to nucleate TBP on a promoter. We propose that p53 successfully nucleates the transcription complex, possibly via direct interaction with TFIID, and activates the EGFR promoter.
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Department of Microbiology, University of Texas Health Science Center at San Antonio 78284.
Muñoz
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Brown
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Subler
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Deb
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D001483:Base Sequence; D001665:Binding Sites; D002478:Cells, Cultured; D015500:Chloramphenicol O-Acetyltransferase; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D016158:Genes, p53 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D011401:Promoter Regions, Genetic
D015500:Chloramphenicol O-Acetyltransferase; D066246:ErbB Receptors