1. Phenobarbital‐induced phosphorylation converts nuclear receptor <scp>ROR</scp> α from a repressor to an activator of the estrogen sulfotransferase gene Sult1e1 in mouse livers
- Author
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Takuyu Hashiguchi, Masahiko Negishi, Myeongjin Yi, Muluneh Fashe, and Rick Moore
- Subjects
Transcriptional Activation ,0301 basic medicine ,Biophysics ,Receptors, Cytoplasmic and Nuclear ,Repressor ,SULT1E1 Gene ,Biochemistry ,Cell Line ,Serine ,Gene Knockout Techniques ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Structural Biology ,Chlorocebus aethiops ,Genetics ,Steroid sulfatase ,Animals ,Humans ,Hypnotics and Sedatives ,Estrogen Sulfotransferase ,Phosphorylation ,Promoter Regions, Genetic ,Molecular Biology ,Constitutive Androstane Receptor ,Activator (genetics) ,Chemistry ,Nuclear Receptor Subfamily 1, Group F, Member 1 ,Cell Biology ,Cell biology ,030104 developmental biology ,Gene Expression Regulation ,Liver ,Nuclear receptor ,Phenobarbital ,030220 oncology & carcinogenesis ,COS Cells ,Sulfotransferases - Abstract
The estrogen sulfotransferase SULT1E1 sulfates and inactivates estrogen, which is reactivated via desulfation by steroid sulfatase, thus regulating estrogen homeostasis. Phenobarbital (PB), a clinical sedative, activates Sult1e1 gene transcription in mouse livers. Here, the molecular mechanism by which the nuclear receptors CAR, which is targeted by PB, and RORα communicate through phosphorylation to regulate Sult1e1 activation has been studied. RORα, a basal activity repressor of the Sult1e1 promoter, becomes phosphorylated at serine 100 and converts to an activator of the Sult1e1 promoter in response to PB. CAR regulates both the RORα phosphorylation and conversion. Our findings suggest that PB signals CAR to communicate with RORα via serine 100 phosphorylation, converting RORα from transcription repressor to activator of the Sult1e1 gene and inducing SULT1E1 expression in mouse livers.
- Published
- 2018
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