Estrogen Receptor-α Binds p53 Tumor Suppressor Protein Directly and Represses Its Function

Estrogen receptor-α (ERα) promotes proliferation of breast cancer cells, whereas tumor suppressor protein p53 impedes proliferation of cells with genomic damage. Whether there is a direct link between these two antagonistic pathways has remained unclear. Here we report that ERα binds directly to p53...

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Bibliographic Details
Published in:The Journal of biological chemistry 2006-04, Vol.281 (15), p.9837-9840
Main Authors: Liu, Wensheng, Konduri, Santhi D., Bansal, Sanjay, Nayak, Bijaya K., Rajasekaran, Sigrid A., Karuppayil, Sankunny M., Rajasekaran, Ayyappan K., Das, Gokul M.
Format: Article
Language:English
Subjects:
Breast Neoplasms - metabolism
Cell Cycle
Cell Line, Tumor
Cell Proliferation
Chromatin Immunoprecipitation
Cyclin-Dependent Kinase Inhibitor p21 - metabolism
Estrogen Receptor alpha - metabolism
Estrogen Receptor alpha - physiology
Gene Expression Regulation, Neoplastic
Genes, p53
Humans
Immunoblotting
Immunoprecipitation
Plasmids - metabolism
Promoter Regions, Genetic
Protein Binding
Protein Structure, Tertiary
Radiation, Ionizing
Reverse Transcriptase Polymerase Chain Reaction
RNA, Small Interfering - metabolism
Time Factors
Transcriptional Activation
Transfection
Transgenes
Tumor Suppressor Protein p53 - metabolism
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Summary:Estrogen receptor-α (ERα) promotes proliferation of breast cancer cells, whereas tumor suppressor protein p53 impedes proliferation of cells with genomic damage. Whether there is a direct link between these two antagonistic pathways has remained unclear. Here we report that ERα binds directly to p53 and represses its function. The activation function-2 (AF-2) domain of ERα and the C-terminal regulatory domain of p53 are necessary for the interaction. Knocking down p53 and ERα by small interfering RNA elicits opposite effects on p53-target gene expression and cell cycle progression. Remarkably, ionizing radiation that causes genomic damage disrupts the interaction between ERα and p53. Ionizing radiation together with ERα knock down results in additive effect on transcription of endogenous p53-target gene p21 (CDKN1) in human breast cancer cells. Our findings reveal a novel mechanism for regulating p53 and suggest that suppressing p53 function is an important component in the proproliferative role of ERα.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.C600001200