JBC

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1074/jbc.M206553200 on August 26, 2002

J. Biol. Chem., Vol. 277, Issue 46, 43691-43697, November 15, 2002
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
277/46/43691    most recent
M206553200v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Grün, F.
Right arrow Articles by Blumberg, B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Grün, F.
Right arrow Articles by Blumberg, B.

Benzoate X Receptors alpha  and beta  Are Pharmacologically Distinct and Do Not Function as Xenobiotic Receptors*

Felix Grün, Ranga N. VenkatesanDagger , Michelle M. Tabb, Changcheng Zhou, Junran Cao, Daniel Hemmati, and Bruce Blumberg§

From the Department of Developmental and Cell Biology, University of California, Irvine, California 92697-2300

The Xenopus benzoate nuclear hormone receptors, BXRalpha and BXRbeta , share 82% identity within their ligand-binding domains and are classified as members of the NR1I2 subfamily that includes the mammalian steroid and xenobiotic receptor, SXR/PXR. Although alkyl benzoates have been identified as endogenous ligands, the exact role of the benzoate receptors in amphibian physiology has not been established. In this report, we show that BXRalpha and BXRbeta are pharmacologically distinct from each other: BXRalpha is more promiscuous than BXRbeta with respect to both ligand specificity and co-activator recruitment. BXRalpha can be transactivated by a number of benzoate derivatives including 4-amino-butylbenzoate (4-ABB), 4-hydroxy-butylbenzoate (4-HBB), 3-hydroxy ethyl benzoate (3-HEB), and benzyl benzoate, but only 4-HBB acts as an agonist for both receptors. Furthermore, BXRalpha -specific agonists such as 4-ABB, chlorpyrifos, and trifluralin act as antagonists on BXRbeta . BXRs are widely distributed in adult tissues but do not show any enrichment in liver and intestine, major sites of SXR/PXR expression that are critical in xenobiotic metabolism. Neither BXR shows the broad specificity toward steroids or xenobiotics exhibited by SXR/PXR. Therefore, we conclude that the BXRs are pharmacologically distinct from each other and unlikely to serve as xenobiotic sensors.

* This work was supported by Grant GM60572 from the National Institutes of Health and a gift from Eisai Co. Ltd. (Japan).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger Present address: Dept. of Pathology, University of Washington Medical School, Seattle, WA, 98195.

§ To whom correspondence should be addressed: Dept. of Developmental and Cell Biology, University of California, 5205 McGaugh Hall, Rm. 5205, Irvine, CA 92697-2300. Tel.: 949-824-8573; Fax: 949-824-4709; E-mail: blumberg@.uci.edu.

Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.


This article has been cited by other articles:


Home page
 Mol. Pharmacol.Home page
C. Zhou, E.-J. Poulton, F. Grun, T. K. Bammler, B. Blumberg, K. E. Thummel, and D. L. Eaton
The Dietary Isothiocyanate Sulforaphane Is an Antagonist of the Human Steroid and Xenobiotic Nuclear Receptor
Mol. Pharmacol., January 1, 2007; 71(1): 220 - 229.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
F. Grun, H. Watanabe, Z. Zamanian, L. Maeda, K. Arima, R. Cubacha, D. M. Gardiner, J. Kanno, T. Iguchi, and B. Blumberg
Endocrine-Disrupting Organotin Compounds Are Potent Inducers of Adipogenesis in Vertebrates
Mol. Endocrinol., September 1, 2006; 20(9): 2141 - 2155.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
J. A. Lavine, A. J. Rowatt, T. Klimova, A. J. Whitington, E. Dengler, C. Beck, and W. H. Powell
Aryl Hydrocarbon Receptors in the Frog Xenopus laevis: Two AhR1 Paralogs Exhibit Low Affinity for 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD)
Toxicol. Sci., November 1, 2005; 88(1): 60 - 72.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
M. D. Krasowski, K. Yasuda, L. R. Hagey, and E. G. Schuetz
Evolution of the Pregnane X Receptor: Adaptation to Cross-Species Differences in Biliary Bile Salts
Mol. Endocrinol., July 1, 2005; 19(7): 1720 - 1739.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
C. Zhou, M. M. Tabb, A. Sadatrafiei, F. Grun, and B. Blumberg
TOCOTRIENOLS ACTIVATE THE STEROID AND XENOBIOTIC RECEPTOR, SXR, AND SELECTIVELY REGULATE EXPRESSION OF ITS TARGET GENES
Drug Metab. Dispos., October 1, 2004; 32(10): 1075 - 1082.
[Abstract] [Full Text] [PDF]

Home page
 Pharmacol. Rev.Home page
C. Handschin and U. A. Meyer
Induction of Drug Metabolism: The Role of Nuclear Receptors
Pharmacol. Rev., December 1, 2003; 55(4): 649 - 673.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. M. Tabb, A. Sun, C. Zhou, F. Grun, J. Errandi, K. Romero, H. Pham, S. Inoue, S. Mallick, M. Lin, et al.
Vitamin K2 Regulation of Bone Homeostasis Is Mediated by the Steroid and Xenobiotic Receptor SXR
J. Biol. Chem., November 7, 2003; 278(45): 43919 - 43927.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2002 by the American Society for Biochemistry and Molecular Biology.