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A novel splicing variant of rat Pregnone X receptor down regulates CYP gene expression.
Author(s) -
Sakai Masaharu,
Nakahara Sho,
Yamada So,
Kurata Yuya,
Yamashita Yoshihumi,
Hayashi Kengo,
Tsutsumi Kaori
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.807.1
Subject(s) - pregnane x receptor , transactivation , nuclear receptor , rna splicing , alternative splicing , biology , microbiology and biotechnology , messenger rna , gene expression , intron , gene , transcription factor , rna , genetics
Pregnane X receptor (PXR) is a nuclear receptor that regulates transcription of both phase I and phase II drug metabolize enzymes. PXR regulate a wide range of biological and physiological processes including drug metabolism and homeostasis of numerous endobiotics. Many alternatively spliced variants of nuclear receptors have been shown to have various effects on the transactivation of the wild‐type receptor. Multiple splicing variants were also identified for the PXR mRNA. Here we report the novel splicing variant mRNA of the rat PXR (PXR‐v). PXR‐v contains 5th intron sequence in the mRNA and it translated into a c‐terminal truncated protein, which lacks a half of the ligand binding domain. This variant mRNA is predominantly expressed in the pre‐neoplastic liver. PXR‐v cDNA transfected hepatoma cells properly expressed variant mRNA and variant protein. The CYP gene, a target gene of PXR, expression was markedly down regulated in these transformants.