THE TUMOR-SUPPRESSOR P53 IS A NEGATIVE REGULATOR OF ESTROGEN-RECEPTORSIGNALING PATHWAYS

The estrogen receptor (ER) is a ligand-dependent transcription factor which regulates growth, development, differentiation and reproduction, To test the hypothesis that the diverse effects of the ER could be me diated by interacting with other transcription factors/oncogenes, the present study assessed its interaction with the tumor suppressor p53. p53 is a transcription factor which is involved in cell cycle regulati on and apoptosis. We found that the wild-type p53 physically interacte d with ER in vivo and repressed the estrogen-activated transcriptional activity. However, p53 mutants had no or reduced repression effect, d epending on the sites of mutation. These findings suggest that p53 can cross talk with the ER in hormone-activated signaling pathways in cel ls. (C) 1997 Academic Press.