PubMed:11875103 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/11875103","sourcedb":"PubMed","sourceid":"11875103","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/11875103","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.","tracks":[{"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"}],"attributes":[{"subj":"T1","pred":"source","obj":"relna"},{"subj":"T2","pred":"source","obj":"relna"},{"subj":"T3","pred":"source","obj":"relna"},{"subj":"T4","pred":"source","obj":"relna"},{"subj":"T5","pred":"source","obj":"relna"},{"subj":"T6","pred":"source","obj":"relna"},{"subj":"T7","pred":"source","obj":"relna"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"relna","color":"#99ec93","default":true}]}]}}