p53 homologue p63 represses epidermal growth factor receptor expression

Tumor suppressor p53 has been shown to transactivate epidermal growth facto r receptor (EGFR) expression through binding to a putative p53 responsive e lement 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. Howev er, our results indicate that TAp63 gamma has a very low ability to bind to the EGFRp53RE and surprisingly represses both basal EGFR promoter activity and e dogenous EGFR expression. Transient transfection a says show that th e EGFR promoter region between -348 and -293, containing two Sp1 sites, is crucial for the repression of the EGFR expression by TAp63 gamma. Mutations in these Spl sites in the reporter constructs result in loss of the TAp63 gamma repression effect. We further show that TAp63 gamma directly interact s with Sp1 by immunoprecipitation analysis and that TAp63 gamma impairs Spl binding to the target DNA site in electrophoretic mobility shift assays. T hese results suggest that TAp63 gamma is involved in the regulation of the EGFR gene expression through interactions with basal transcription factors.