Identification of a liver-specific uridine phosphorylase that is regulated by multiple lipid-sensing nuclear receptors.
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 liver X receptors, peroxisome proliferator-activated receptor alpha, farnesoid X receptor, and hepatic nuclear factor-4alpha), 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, nonoverlapping 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.
Zhang
Yuan
Y
Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9050, USA.
Repa
Joyce J
JJ
Inoue
Yusuke
Y
Hayhurst
Graham P
GP
Gonzalez
Frank J
FJ
Mangelsdorf
David J
DJ
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D051557:Hepatocyte Nuclear Factor 4; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D014543:Uridine Phosphorylase / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D051557:Hepatocyte Nuclear Factor 4; D010750:Phosphoproteins; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; C099713:nuclear receptor subfamily 0, group B, member 2; D014543:Uridine Phosphorylase