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p53 Homologue p63 Represses Epidermal Growth Factor Receptor Expression

Tumor suppressor p53 has been shown to transactivate epidermal growth factor receptor (EGFR) expression through binding to a putative p53 responsive element in the EGFR promoter between nucleotides −265 and −239 (EGFRp53RE). Isotypes of p63 gene products, recently identified as p53 relatives, have a...

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Bibliographic Details
Published in:The Journal of biological chemistry 2001-11, Vol.276 (45), p.41717-41724
Main Authors: Nishi, Hirotaka, Senoo, Makoto, Nishi, Katsura H., Murphy, Barbara, Rikiyama, Toshiki, Matsumura, Yasuko, Habu, Sonoko, Johnson, Alfred C.
Format: Article
Language:English
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Summary:Tumor suppressor p53 has been shown to transactivate epidermal growth factor receptor (EGFR) expression through binding to a putative p53 responsive element in the EGFR promoter between nucleotides −265 and −239 (EGFRp53RE). Isotypes of p63 gene products, recently identified as p53 relatives, have a similar function to transactivate several p53 target gene promoters. However, our results indicate that TAp63γ has a very low ability to bind to the EGFRp53RE and surprisingly represses both basal EGFR promoter activity and endogenous EGFR expression. Transient transfection assays show that the EGFR promoter region between −348 and −293, containing two Sp1 sites, is crucial for the repression of the EGFR expression by TAp63γ. Mutations in these Sp1 sites in the reporter constructs result in loss of the TAp63γ repression effect. We further show that TAp63γ directly interacts with Sp1 by immunoprecipitation analysis and that TAp63γ impairs Sp1 binding to the target DNA site in electrophoretic mobility shift assays. These results suggest that TAp63γ is involved in the regulation of the EGFR gene expression through interactions with basal transcription factors.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M101241200