PubMed:11875103 JSONTXT

{"project":"relna","denotations":[{"id":"T1","span":{"begin":41,"end":48},"obj":"DNA"},{"id":"T2","span":{"begin":207,"end":214},"obj":"DNA"},{"id":"T3","span":{"begin":402,"end":409},"obj":"DNA"},{"id":"T4","span":{"begin":462,"end":465},"obj":"Protein"},{"id":"T5","span":{"begin":621,"end":624},"obj":"Protein"},{"id":"T6","span":{"begin":920,"end":923},"obj":"Protein"},{"id":"T7","span":{"begin":954,"end":961},"obj":"DNA"}],"relations":[{"id":"R0","pred":"linked","subj":"T4","obj":"T3"}],"text":"A negative coregulator for the human ER.\nERalpha is a ligand-activated transcription factor and a key regulator of the processes involved in cellular proliferation and differentiation. In addition, aberrant ERalpha activity is linked to several pathological conditions including breast cancer. A complex network of coregulatory proteins is largely believed to determine the transcriptional activity of ERalpha. We report here the isolation of a protein, denoted RTA for repressor of tamoxifen transcriptional activity, which contains an RNA recognition motif and interacts with the receptor N-terminal activation domain. RTA interacts with RNA in vitro, and its overexpression inhibits the partial agonist activity manifest by the antiestrogen tamoxifen while minimally affecting E2-activated transcription. Mutation of the RNA recognition motif alters RNA binding specificity and results in a dominant negative form of RTA that leads to derepression of ERalpha transcriptional activity, allowing all classes of antiestrogens to manifest partial agonist activity and enhancing agonist efficacy. These findings suggest a role for RNA binding proteins as coregulatory factors of the nuclear receptor family and reveal a novel mechanism by which antiestrogens can manifest agonist activities in some tissues."}