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Molecular and Cellular Biology, June 2007, p. 4416-4430, Vol. 27, No. 12
0270-7306/07/$08.00+0 doi:10.1128/MCB.02314-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7248
Received 11 December 2006/ Returned for modification 10 January 2007/ Accepted 24 March 2007
A number of studies have identified cytosolic prostaglandin E2 synthase (cPGES)/p23 as a cytoplasmic protein capable of metabolism of prostaglandin E2 (PGE2) from the cyclooxygenase metabolite prostaglandin endoperoxide (PGH2). However, this protein has also been implicated in a number of other pathways, including stabilization of the glucocorticoid receptor (GR) complex. To define the importance of the functions assigned to this protein, mice lacking detectible cPGES/p23 expression were generated. cPGES/p23/ pups die during the perinatal period and display retarded lung development reminiscent of the phenotype of GR-deficient neonates. Furthermore, GR-sensitive gluconeogenic enzymes are not induced in the prenatal period. However, unlike GR-deficient embryos, cPGES/p23/ embryos are small and a proliferation defect is observed in cPGES/p23/ fibroblasts. Analysis of arachidonic acid metabolites in embryonic tissues and primary fibroblasts failed to support a function for this protein in PGE2 biosynthesis. Thus, while the growth retardation of the cPGES/p23/ pups and decreased proliferation of primary fibroblasts identify functions for this protein in addition to GR stabilization, it is unlikely that these functions include metabolism of PGH2 to PGE2.
Published ahead of print on 16 April 2007.
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