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Whereas SULT1E1 is expressed low in the liver of adult mice, it is induced by phenobarbital (PB) treatment or spontaneously in diabetic livers <jats:italic>via<\/jats:italic> nuclear receptors. Utilizing constitutive active\/androstane receptor (CAR) KO, estrogen receptor \u03b1 (ER\u03b1 KO, phosphorylation-blocked ER\u03b1 S216A KI mice, it is now demonstrated that, after being activated by PB, CAR binds and recruits ER\u03b1 onto the <jats:italic>Sulte1<\/jats:italic> promoter for subsequent phosphorylation at Ser216. This phosphorylation tightens CAR interacting with ER\u03b1 and to activates the promoter. Hepatic SULT1E1 mRNA levels are constitutively up-regulated in type 1 diabetic Akita mice; CAR spontaneously accumulates in the nucleus and activates the <jats:italic>Sult1e1<\/jats:italic> promoter by recruiting phosphorylated ER\u03b1 in the liver as observed with PB-induced livers. Thus, this CAR-phosphorylated ER\u03b1 signaling enables these two nuclear receptors to communicate, activating the <jats:italic>Sult1e1<\/jats:italic> gene in response to either PB or diabetes in mice. ER\u03b1 phosphorylation may integrate CAR into estrogen actions, providing insights into understanding drug-hormone interactions in clinical therapy.<\/jats:p>","DOI":"10.1038\/s41598-020-61767-9","type":"journal-article","created":{"date-parts":[[2020,3,19]],"date-time":"2020-03-19T11:04:07Z","timestamp":1584615847000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Nuclear receptor CAR-ER\u03b1 signaling regulates the estrogen sulfotransferase gene in the liver"],"prefix":"10.1038","volume":"10","author":[{"given":"MyeongJin","family":"Yi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muluneh","family":"Fashe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shingo","family":"Arakawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rick","family":"Moore","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatsuya","family":"Sueyoshi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masahiko","family":"Negishi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,3,19]]},"reference":[{"key":"61767_CR1","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.steroids.2014.06.012","volume":"90","author":"I Paterni","year":"2014","unstructured":"Paterni, I., Granchi, C., Katzenellenbogen, J. 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