Phenobarbital-induced phosphorylation converts nuclear receptor RORα from a repressor to an activator of the estrogen sulfotransferase gene Sult1e1 in mouse livers.
FEBS Lett
; 592(16): 2760-2768, 2018 08.
Article
in En
| MEDLINE
| ID: mdl-30025153
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Phenobarbital
/
Sulfotransferases
/
Receptors, Cytoplasmic and Nuclear
/
Nuclear Receptor Subfamily 1, Group F, Member 1
/
Hypnotics and Sedatives
Limits:
Animals
/
Humans
Language:
En
Journal:
FEBS Lett
Year:
2018
Type:
Article
Affiliation country:
United States