Estrogen receptor protects p53 from deactivation by human double minute-2.

We and others have demonstrated that estrogen receptor alpha (ERalpha) and p53, two important regulatory proteins in breast cancer, bind to each other. In this report, using the glutathione S-transferase pull-down methodology, we show the ligand-independent interaction of ERalpha with the NH2-terminal region of p53, a region known to bind ...
the p300 and human double minute-2 (hdm2) regulatory factors. Furthermore, we have demonstrated that ERalpha is capable of binding hdm2 directly. The interaction of ERalpha and p53 does not interfere with the binding between p53 and hdm2; rather, these proteins form a ternary complex. The effect of ERalpha on the p53-hdm2 regulatory loop has been examined. Our results indicate that ERalpha protects p53 from being deactivated by hdm2. It is evident from these investigations that the ligand-independent protection of p53 by ERalpha is a novel role for this protein in addition to its classic regulatory function as a ligand-inducible transcription factor. This study also describes a new mechanism of cellular regulation of p53 activity.
Mesh Terms:
Breast Neoplasms, Estrogen Receptor alpha, Female, Glutathione Transferase, Hela Cells, Humans, Neoplasm Proteins, Nuclear Proteins, Polymerase Chain Reaction, Protein Biosynthesis, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-mdm2, Receptors, Estrogen, Recombinant Fusion Proteins, Transfection, Tumor Cells, Cultured, Tumor Suppressor Protein p53
Cancer Res.
Date: Apr. 01, 2000
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