Identification of an additional p53-responsive site in the human epidermal growth factor receptor gene promotor.
Exogenously introduced wild-type and mutant p53 have recently been reported to enhance the human epidermal growth factor receptor (EGF-R) gene promoter activity in p53-deficient Saos2 osteosarcoma cells. A p53 binding site residing at position -265/-239 in the EGF-R proximal promoter has also been identified. We investigated the p53 regulation of EGF-R core promoter activity in human cell lines with varying endogenour p53 status. Wild-type and mutant p53Ala143 enhanced the EGF-R core promotor activity in cells that were either p53-deficient or contained wild-type or mutant endogenous p53. Upon further characterization of the various deletion fragments of the EGF-R promoter, we identified a wild-type p53 responsive 62 bp region residing at position -167/-105. The -167/-105 segment was responsive only to wild-type p53 but not to mutant p53Ala143 or p53His273. The -167/-105 segment of the EGF-R promotor contains one perfect and several imperfect consensus p53-binding half sites; indeed in gel shift experiments the 62 bp -167/-105 segment as well as the oligonucleotides corresponding to two p53 consensus half-sites within the 62 bp fragment, exhibited binding to p53-containing protein complexes. Thus, we have identified an additional wild-type p53 responsive site in the human EGF-R promoter. This site containing consensus p53-binding sequences resides at position -167/-105 and is proximal to recently identified p53 binding element located at position -265/-239 in the EGF-R promotor.
Sheikh
M S
MS
Laboratory of Molecular Pharmacology, National Cancer Institute, Bethesda, Maryland 20892, USA.
Carrier
F
F
Johnson
A C
AC
Ogdon
S E
SE
Fornace
A J
AJ
D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D011401:Promoter Regions, Genetic; D017384:Sequence Deletion; D014407:Tumor Cells, Cultured
D066246:ErbB Receptors