MODULATION OF CELL-PROLIFERATION AND GENE-EXPRESSION BY A P53-ESTROGEN RECEPTOR HYBRID PROTEIN

We report that p53her, a chimeric protein consisting of the complete h uman wild-type p53 and the human estrogen receptor hormone-binding dom ain, strongly suppresses proliferation and induces characteristic morp hological changes in Saos-2 human osteosarcoma cells when induced by 1 7beta-estradiol. In contrast, p53her constitutively transactivates a p 53-responsive promoter in transfection assays, so that transactivation is not regulated by estradiol. However, coexpression of p53her and on coprotein MDM-2, which associates with and presumably inactivates p53, results in suppression of p53her-mediated transactivation in the abse nce, but not the presence, of estradiol. Similarly, p53her induces exp ression of an endogenous MDM-2 transcript only in the presence of estr adiol. These results suggest a correlation between the growth suppress or function of p53her and release of a transactivation block mediated by MDM-2.