Molecular mechanism of nuclear translocation of an orphan nuclear receptor

The steroid and xenobiotic receptor (SXR) is an orphan nuclear receptor that plays a key role in the regulation of xenobiotic response by controlling the expression of drug metabolizing and clearance enzymes. We observed that pregnane X receptor (PXR), the mouse ortholog of SXR, was retained in the cyto-plasm of hepatic cells of untreated mice, whereas PXR was translocated to the nucleus after administration of a ligand, pregnenolone 16-carbonitrile. To understand the molecular mechanisms underlying the xenochemical-dependent nuclear translocation of SXR, we identified the signal sequence of SXR that regulates its nuclear translocation; using an in vitro expres-sion system, we allocated the nuclear localization signal (NLS) to amino acid residues 66 to 92 within the DNA binding domain of SXR. The NLS of SXR is characterized as the bipartite type