![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 63, Issue 3, 524-531, March 2003
Research Institute, Saitama Cancer Center, Saitama, Japan
(K.Kawana, T.I., K.Kawajiri); Tokyo University of Science, Tokyo, Japan
(K.Kawana, K.T.); Department of Pathology, Saitama Cancer Center,
Saitama, Japan (Y.K.); Computational Biology Research Center, National
Institute of Advanced Industrial Science and Technology, Tokyo, Japan
(O.G.); Core Research for Evolutional Science and Technology (CREST),
Japan Science and Technology Corporation, Saitama, Japan (K.T.,
K.Kawajiri)
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 cytoplasm 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 expression 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, and is recognized by the three
molecular species of importin : Rch1 (PTAC58), NPI1, and Qip1, in
the presence of PTAC97 of importin 
to target the nuclear pore. The
nuclear translocation of SXR was observed as an essential regulatory
event for transcription of its target genes such as
CYP3A4. These results strongly suggest that the
molecular mechanism of the nuclear import of SXR was different from
that of another xenosensor, the constitutively active receptor, whose
translocation into the nucleus is mediated by a leucine-rich
xenochemical response signal in its ligand binding domain.
This article has been cited by other articles:
|
|
 |
|
  H. Wang, H. Li, L. B. Moore, M. D. L. Johnson, J. M. Maglich, B. Goodwin, O. R. R. Ittoop, B. Wisely, K. Creech, D. J. Parks, et al. The Phytoestrogen Coumestrol Is a Naturally Occurring Antagonist of the Human Pregnane X Receptor Mol. Endocrinol., April 1, 2008; 22(4): 838 - 857. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Sueyoshi, R. Moore, J. Sugatani, Y. Matsumura, and M. Negishi PPP1R16A, The Membrane Subunit of Protein Phosphatase 1{beta}, Signals Nuclear Translocation of the Nuclear Receptor Constitutive Active/Androstane Receptor Mol. Pharmacol., April 1, 2008; 73(4): 1113 - 1121. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Sun, V. Montana, K. Chellappa, Y. Brelivet, D. Moras, Y. Maeda, V. Parpura, B. M. Paschal, and F. M. Sladek Phosphorylation of a Conserved Serine in the Deoxyribonucleic Acid Binding Domain of Nuclear Receptors Alters Intracellular Localization Mol. Endocrinol., June 1, 2007; 21(6): 1297 - 1311. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Itoh, M. Nakajima, E. Higashi, R. Yoshida, K. Nagata, Y. Yamazoe, and T. Yokoi Induction of Human CYP2A6 Is Mediated by the Pregnane X Receptor with Peroxisome Proliferator-Activated Receptor-{gamma} Coactivator 1{alpha} J. Pharmacol. Exp. Ther., November 1, 2006; 319(2): 693 - 702. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Zhang, M.-L. Noordine, C. Cherbuy, P. Vaugelade, J. M. Pascussi, P.-H. Duee, and M. Thomas Different activation patterns of rat xenobiotic metabolism genes by two constituents of garlic Carcinogenesis, October 1, 2006; 27(10): 2090 - 2095. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Miki, T. Suzuki, K. Kitada, N. Yabuki, R. Shibuya, T. Moriya, T. Ishida, N. Ohuchi, B. Blumberg, and H. Sasano Expression of the Steroid and Xenobiotic Receptor and Its Possible Target Gene, Organic Anion Transporting Polypeptide-A, in Human Breast Carcinoma Cancer Res., January 1, 2006; 66(1): 535 - 542. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Aouabdi, G. Gibson, and N. Plant TRANSCRIPTIONAL REGULATION OF THE PXR GENE: IDENTIFICATION AND CHARACTERIZATION OF A FUNCTIONAL PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR {alpha} BINDING SITE WITHIN THE PROXIMAL PROMOTER OF PXR Drug Metab. Dispos., January 1, 2006; 34(1): 138 - 144. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. R. Johnson, C.-W. Li, L.-Y. Chen, J. C. Ghosh, and J. D. Chen Regulation and Binding of Pregnane X Receptor by Nuclear Receptor Corepressor Silencing Mediator of Retinoid and Thyroid Hormone Receptors (SMRT) Mol. Pharmacol., January 1, 2006; 69(1): 99 - 108. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Orans, D. G. Teotico, and M. R. Redinbo The Nuclear Xenobiotic Receptor Pregnane X Receptor: Recent Insights and New Challenges Mol. Endocrinol., December 1, 2005; 19(12): 2891 - 2900. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Mani, H. Huang, S. Sundarababu, W. Liu, G. Kalpana, A. B. Smith, and S. B. Horwitz Activation of the Steroid and Xenobiotic Receptor (Human Pregnane X Receptor) by Nontaxane Microtubule-Stabilizing Agents Clin. Cancer Res., September 1, 2005; 11(17): 6359 - 6369. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Tang, J. H. Lin, and A. Y. H. Lu METABOLISM-BASED DRUG-DRUG INTERACTIONS: WHAT DETERMINES INDIVIDUAL VARIABILITY IN CYTOCHROME P450 INDUCTION? Drug Metab. Dispos., May 1, 2005; 33(5): 603 - 613. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. J. Squires, T. Sueyoshi, and M. Negishi Cytoplasmic Localization of Pregnane X Receptor and Ligand-dependent Nuclear Translocation in Mouse Liver J. Biol. Chem., November 19, 2004; 279(47): 49307 - 49314. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Bhalla, C. Ozalp, S. Fang, L. Xiang, and J. K. Kemper Ligand-activated Pregnane X Receptor Interferes with HNF-4 Signaling by Targeting a Common Coactivator PGC-1{alpha}: FUNCTIONAL IMPLICATIONS IN HEPATIC CHOLESTEROL AND GLUCOSE METABOLISM J. Biol. Chem., October 22, 2004; 279(43): 45139 - 45147. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Swales and M. Negishi CAR, Driving into the Future Mol. Endocrinol., July 1, 2004; 18(7): 1589 - 1598. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Chen, S. S. Ferguson, M. Negishi, and J. A. Goldstein Induction of Human CYP2C9 by Rifampicin, Hyperforin, and Phenobarbital Is Mediated by the Pregnane X Receptor J. Pharmacol. Exp. Ther., February 1, 2004; 308(2): 495 - 501. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Koyano, K. Kurose, Y. Saito, S. Ozawa, R. Hasegawa, K. Komamura, K. Ueno, S. Kamakura, M. Kitakaze, T. Nakajima, et al. FUNCTIONAL CHARACTERIZATION OF FOUR NATURALLY OCCURRING VARIANTS OF HUMAN PREGNANE X RECEPTOR (PXR): ONE VARIANT CAUSES DRAMATIC LOSS OF BOTH DNA BINDING ACTIVITY AND THE TRANSACTIVATION OF THE CYP3A4 PROMOTER/ENHANCER REGION Drug Metab. Dispos., January 1, 2004; 32(1): 149 - 154. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Chen, S. S. Ferguson, M. Negishi, and J. A. Goldstein Identification of Constitutive Androstane Receptor and Glucocorticoid Receptor Binding Sites in the CYP2C19 Promoter Mol. Pharmacol., August 1, 2003; 64(2): 316 - 324. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
