ERR-10: a new repressor in transcriptional signaling activation of estrogen receptor-α

Abstract

Estrogen receptor-alpha (ER-α) is a nuclear transcriptional factor that is part of the nuclear receptor superfamily. In this study, we isolated and identified a new L XXLL-containing protein that interacts with the ER-α via a yeast two-hybrid assay. We have termed this protein estrogen receptor repressor-10 (ERR-10). The ERR-10 cDNA is predicted to encode a polypeptide of 94 amino acids, with a molecular mass of about 10 kDa. Although the ERR-10 mRNA transcript is expressed in a wide range of normal human tissues, higher expression levels are found in endocrinal tissues relative to other tissues. We have demonstrated, through immunoprecipitation, Western blot and GST pull-down assays, that ERR-10 associates with ER-α. Moreover, ERR-10 decreased 17β-estrodial-induced activation of ER-α transcriptional activity in transient transfection assays of mammalian cells. The ERR-10 N-terminus, which resembles two L XXLL motifs, is essential for ER-α binding and repression activity. Estrogen modulation of estrogen-responsive gene expression was markedly blocked by ERR-10. These results suggest that ERR-10 is a novel mediator in ER transcriptional activation.