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
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
PubMed ID: 10766163
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