ERR-10: a new repressor in transcriptional signaling activation of estrogen receptor-alpha.
Estrogen receptor-alpha (ER-alpha) is a nuclear transcriptional factor that is part of the nuclear receptor superfamily. In this study, we isolated and identified a new LXXLL-containing protein that interacts with the ER-alpha 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-alpha. Moreover, ERR-10 decreased 17beta-estrodial-induced activation of ER-alpha transcriptional activity in transient transfection assays of mammalian cells. The ERR-10 N-terminus, which resembles two LXXLL motifs, is essential for ER-alpha 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.
Department of Oncology, Lombardi Compreshensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057, USA.
Qinghui
Q
Meng
Zeguo
Z
Zhao
Ming
M
Yan
Lixin
L
Zhou
Jiyou
J
Li
Christina
C
Kitt
Gao
G
Bin
Saijun
S
Fan
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001483:Base Sequence; D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000737:chemistry / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008969:Molecular Sequence Data; D008970:Molecular Weight; D011233:Precipitin Tests; D017434:Protein Structure, Tertiary; D062085:RNA, Long Noncoding; D011960:Receptors, Estrogen / Q000378:metabolism*; D012097:Repressor Proteins / Q000737:chemistry / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D020798:Two-Hybrid System Techniques
D047628:Estrogen Receptor alpha; D062085:RNA, Long Noncoding; D011960:Receptors, Estrogen; D012097:Repressor Proteins; C493108:estrogen receptor repressor-10, human; D004958:Estradiol