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This version published online on January 8, 2004
Molecular Endocrinology, doi:10.1210/me.2003-0285
Molecular Endocrinology Vol. 0, No. 2004 200302852-
doi:10.1210/me.2003-0285
Copyright © 2004 by the Endocrine Society.
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Submitted on July 18, 2003
Accepted on December 23, 2003

Identification of a liver-specific uridine phosphorylase that is regulated by multiple lipid-sensing nuclear receptors

Yuan Zhang, Joyce J. Repa, Yusuke Inoue, Graham P. Hayhurst, Frank J. Gonzalez, and David J. Mangelsdorf*

Department of Pharmacology and Howard Hughes Medical Institute, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390-9050; Departments of Physiology and Internal Medicine, Touchstone Center for Diabetes Research, UT Southwestern Medical Center at Dallas, Dallas, TX 75390-8854; Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892; Current address: Unité de Génétique de la Différenciation, Département de Biologie du Développement, 25/28, Rue du Dr. Roux, Institut Pasteur, 75724 Paris Cedex 15, France

* To whom correspondence should be addressed. E-mail: Davo.Mango{at}utsouthwestern.edu.

In this work, we report the characterization of a novel liver-specific gene (L-UrdPase) whose expression is regulated by a number of hepatic nuclear receptors (including LXRs, PPAR{alpha}, FXR, and HNF-4{alpha}), which have been shown to be involved in lipid metabolism. L-UrdPase encodes a previously uncharacterized protein with similarity to an intestine-specific uridine phosphorylase. Enzymatic assays confirmed that L-UrdPase has uridine phosphorylase activity. However, L-UrdPase has a highly restricted, non-overlapping pattern of expression with its intestinal counterpart and is regulated in a distinct manner by several different nuclear receptors. The identification of the liver uridine phosphorylase and its characterization as a target of lipid-sensing nuclear receptors implies the existence of a previously unknown nuclear receptor signaling pathway that links lipid and uridine metabolism.
Key words: nuclear receptors • uridine phosphorylase • liver • lipid metabolism

NURSA Molecule Pages Link:

Nuclear Receptors:   SHP  |  PPARα  |  LXRβ  |  LXRα  |  FXRα  |  PXR  |  HNF4α
Ligands:   Pregnenolone carbonitrile  |  LGD 100268  |  T0901317





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