PT  - JOURNAL ARTICLE
AU  - Masahiko Negishi
TI  - Phenobarbital Meets Phosphorylation of Nuclear Receptors
AID  - 10.1124/dmd.116.074872
DP  - 2017 May 01
TA  - Drug Metabolism and Disposition
PG  - 532--539
VI  - 45
IP  - 5
4099  - http://dmd.aspetjournals.org/content/45/5/532.short
4100  - http://dmd.aspetjournals.org/content/45/5/532.full
SO  - Drug Metab Dispos2017 May 01; 45
AB  - Phenobarbital was the first therapeutic drug to be characterized for its induction of hepatic drug metabolism. Essentially at the same time, cytochrome P450, an enzyme that metabolizes drugs, was discovered. After nearly 50 years of investigation, the molecular target of phenobarbital induction has now been delineated to phosphorylation at threonine 38 of the constitutive androstane receptor (NR1I3), a member of the nuclear receptor superfamily. Determining this mechanism has provided us with the molecular basis to understand drug induction of drug metabolism and disposition. Threonine 38 is conserved as a phosphorylation motif in the majority of both mouse and human nuclear receptors, providing us with an opportunity to integrate diverse functions of nuclear receptors. Here, I review the works and accomplishments of my laboratory at the National Institutes of Health National Institute of Environmental Health Sciences and the future research directions of where our study of the constitutive androstane receptor might take us.