PubMed:10409727 JSONTXT

{"project":"PMID_GLOBAL","denotations":[{"id":"T1","span":{"begin":304,"end":306},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T2","span":{"begin":399,"end":401},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T3","span":{"begin":474,"end":476},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T4","span":{"begin":483,"end":485},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T5","span":{"begin":557,"end":559},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T6","span":{"begin":966,"end":968},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T7","span":{"begin":979,"end":981},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T8","span":{"begin":1161,"end":1163},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T9","span":{"begin":1169,"end":1171},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T10","span":{"begin":1367,"end":1369},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T11","span":{"begin":1415,"end":1418},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T12","span":{"begin":1547,"end":1549},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T13","span":{"begin":1645,"end":1647},"obj":"DiseaseOrPhenotypicFeature"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"0004981"},{"id":"A2","pred":"mondo_id","subj":"T2","obj":"0004981"},{"id":"A3","pred":"mondo_id","subj":"T3","obj":"0004981"},{"id":"A4","pred":"mondo_id","subj":"T4","obj":"0004981"},{"id":"A5","pred":"mondo_id","subj":"T5","obj":"0004981"},{"id":"A6","pred":"mondo_id","subj":"T6","obj":"0004981"},{"id":"A7","pred":"mondo_id","subj":"T7","obj":"0004981"},{"id":"A8","pred":"mondo_id","subj":"T8","obj":"0004981"},{"id":"A9","pred":"mondo_id","subj":"T9","obj":"0004981"},{"id":"A10","pred":"mondo_id","subj":"T10","obj":"0004981"},{"id":"A11","pred":"mondo_id","subj":"T11","obj":"0010565"},{"id":"A12","pred":"mondo_id","subj":"T12","obj":"0004981"},{"id":"A13","pred":"mondo_id","subj":"T13","obj":"0004981"}],"text":"Purification and identification of p68 RNA helicase acting as a transcriptional coactivator specific for the activation function 1 of human estrogen receptor alpha.\nThe estrogen receptor (ER) regulates the expression of target genes in a ligand-dependent manner. The ligand-dependent activation function AF-2 of the ER is located in the ligand binding domain (LBD), while the N-terminal A/B domain (AF-1) functions in a ligand-independent manner when isolated from the LBD. AF-1 and AF-2 exhibit cell type and promoter context specificity. Furthermore, the AF-1 activity of the human ERalpha (hERalpha) is enhanced through phosphorylation of the Ser(118) residue by mitogen-activated protein kinase (MAPK). From MCF-7 cells, we purified and cloned a 68-kDa protein (p68) which interacted with the A/B domain but not with the LBD of hERalpha. Phosphorylation of hERalpha Ser(118) potentiated the interaction with p68. We demonstrate that p68 enhanced the activity of AF-1 but not AF-2 and the estrogen-induced as well as the anti-estrogen-induced transcriptional activity of the full-length ERalpha in a cell-type-specific manner. However, it did not potentiate AF-1 or AF-2 of ERbeta, androgen receptor, retinoic acid receptor alpha, or mineralocorticoid receptor. We also show that the RNA helicase activity previously ascribed to p68 is dispensable for the ERalpha AF-1 coactivator activity and that p68 binds to CBP in vitro. Furthermore, the interaction region for p68 in the ERalpha A/B domain was essential for the full activity of hERalpha AF-1. Taken together, these findings show that p68 acts as a coactivator specific for the ERalpha AF-1 and strongly suggest that the interaction between p68 and the hERalpha A/B domain is regulated by MAPK-induced phosphorylation of Ser(118)."}

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