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Phenobarbital‐induced phosphorylation converts nuclear receptor ROR α from a repressor to an activator of the estrogen sulfotransferase gene Sult1e1 in mouse livers
Author(s) -
Fashe Muluneh,
Hashiguchi Takuyu,
Yi MyeongJin,
Moore Rick,
Negishi Masahiko
Publication year - 2018
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13199
Subject(s) - phosphorylation , repressor , activator (genetics) , nuclear receptor , chemistry , transcription factor , estrogen related receptor gamma , estrogen receptor , hdac1 , microbiology and biotechnology , estrogen receptor beta , serine , biology , gene , biochemistry , histone deacetylase , histone , genetics , cancer , breast cancer
The estrogen sulfotransferase SULT 1E1 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 ROR α communicate through phosphorylation to regulate Sult1e1 activation has been studied. ROR α, 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 ROR α phosphorylation and conversion. Our findings suggest that PB signals CAR to communicate with ROR α via serine 100 phosphorylation, converting ROR α from transcription repressor to activator of the Sult1e1 gene and inducing SULT 1E1 expression in mouse livers.