Transcriptional Suppression of the Estrogen Receptor by Truncated Estrogen Receptor-Alpha

Abstract

The estrogen receptor (ER) is composed of six major functional domains - the A/B domain as the activation function 1 domain, domain C as the DNA-binding domain, domain D as a hinge domain, and domain E/F as the ligand-dependent transcriptional domains. A novel protein (designated as SRB-RGS) that interacted with domains C and D of ERα (ERα C/D) repressed the transcriptional activity of ERα. In this study, we have examined whether ERα C/D releases transcriptional suppression of ERα by intrinsic SRB-RGS. The expression vector of ERα C/D was transfected to the human cancer cell, KPL-1, which expressed the intrinsic ER. Unexpectedly, transcriptional suppression of ER by ERα C/D was observed. COS-7 cells, which have no intrinsic ER, showed a similar suppression of ERα by co-transfection of ERα and ERα C/D. The DNA-binding and the estrogen-binding activities of ERα decreased on co-transfection of ERα C/D, suggesting a decrease in the receptor protein itself. It is likely that the degradation of ER by co-transfection caused the transcriptional suppression of the ER.

Key words

Dominant Negative - DNA-Binding Domain - SRB-RGS - Degradation - Breast Cancer Cell - COS-7 Cell - Gel-Shift Assay

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