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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.

cPGES/p23 Is Required for Glucocorticoid Receptor Function and Embryonic Growth but Not Prostaglandin E2 Synthesis{triangledown}

Alysia Kern Lovgren, Martina Kovarova, and Beverly H. Koller*

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.


* Corresponding author. Mailing address: University of North Carolina, Department of Medicine, 4341 Molecular Biomedical Research Bldg., Chapel Hill, NC 27599. Phone: (919) 962-2153. Fax: (919) 843-4682. E-mail: treawouns{at}aol.com

{triangledown} Published ahead of print on 16 April 2007.


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.




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