title: Modulation of cell proliferation and gene expression by a p53-estrogen receptor hybrid protein.
abstract: We report that p53her, a chimeric protein consisting of the complete human wild-type p53 and the human estrogen receptor hormone-binding domain, strongly suppresses proliferation and induces characteristic morphological changes in Saos-2 human osteosarcoma cells when induced by 17 beta-estradiol. In contrast, p53her constitutively transactivates a p53-responsive promoter in transfection assays, so that transactivation is not regulated by estradiol. However, coexpression of p53her and oncoprotein MDM-2, which associates with and presumably inactivates p53, results in suppression of p53her-mediated transactivation in the absence, but not the presence, of estradiol. Similarly, p53her induces expression of an endogenous MDM-2 transcript only in the presence of estradiol. These results suggest a correlation between the growth suppressor function of p53her and release of a transactivation block mediated by MDM-2.
authors.affiliation: Center for Molecular Genetics, University of California, San Diego, La Jolla 92093-0634.
authors.forename: K
authors.initials: K
authors.lastname: Roemer
authors.forename: T
authors.initials: T
authors.lastname: Friedmann
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002455:Cell Division; D004958:Estradiol / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D011960:Receptors, Estrogen / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D011960:Receptors, Estrogen; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D013629:Tamoxifen; D004958:Estradiol