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Molecular Identification of Cytosolic Prostaglandin E2 Synthase That Is Functionally Coupled with Cyclooxygenase-1 in Immediate Prostaglandin E2Biosynthesis
Open accessAbstract
Here we report the molecular identification of cytosolic glutathione (GSH)-dependent prostaglandin (PG) E(2) synthase (cPGES), a terminal enzyme of the cyclooxygenase (COX)-1-mediated PGE(2) biosynthetic pathway. GSH-dependent PGES activity in the cytosol of rat brains, but not of other tissues, increased 3-fold after lipopolysaccharide (LPS) challenge. Peptide microsequencing of purified enzyme revealed that it was identical to p23, which is reportedly the weakly bound component of the steroid hormone receptor/hsp90 complex. Recombinant p23 expressed in Escherichia coli and 293 cells exhibited all the features of PGES activity detected in rat brain cytosol. A tyrosine residue near the N terminus (Tyr(9)), which is known to be critical for the activity of cytosolic GSH S-transferases, was essential for PGES activity. The expression of cPGES/p23 was constitutive and was unaltered by proinflammatory stimuli in various cells and tissues, except that it was increased significantly in rat brain after LPS treatment. cPGES/p23 was functionally linked with COX-1 in marked preference to COX-2 to produce PGE(2) from exogenous and endogenous arachidonic acid, the latter being supplied by cytosolic phospholipase A(2) in the immediate response. Thus, functional coupling between COX-1 and cPGES/p23 may contribute to production of the PGE(2) that plays a role in maintenance of tissue homeostasis.
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In the citing paper
“PTGES3 is also reported to be a cytosolic prostaglandin synthase that converts Prostaglandin H2 (PGH2) to Prostaglandin E2 (PGE2)47”
From Genome-scale CRISPR screens identify PTGES3 as a direct modulator of androgen receptor function in advanced prostate cancer (2025) · cites this paper as [47]
In the citing paper
“PTGES3 protein is reported to have several protein functions and to be localized to both the cytosol and nucleus41–49 (Fig. 3f).”
From Genome-scale CRISPR screens identify PTGES3 as a direct modulator of androgen receptor function in advanced prostate cancer (2025) · cites this paper as [47]
In the citing paper
“The proposed PGE2 enzymatic site is at the N terminus of the protein whereas the proposed HSP90 interaction motif is at the C terminus of the protein41,47.”
From Genome-scale CRISPR screens identify PTGES3 as a direct modulator of androgen receptor function in advanced prostate cancer (2025) · cites this paper as [47]
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Metadata
- Authors
- Tanioka, T., Nakatani, Y., Semmyo, N., Murakami, M., & Kudo, I.
- Affiliations
- SHOWA Medical University (JP)
- Corresponding author
- Kudo, Ichiro
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2000-10
- Volume
- 275
- Issue
- 42
- Pages
- 32775-32782
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2077641423
- Cited by
- 708
- References
- 41
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 6 · 2023: 15 · 2022: 9 · 2021: 12 · 2020: 14 · 2019: 19 · 2018: 13 · 2017: 19 · 2016: 15 · 2015: 17 · 2014: 31 · 2013: 30 · 2012: 32
- FWCI
- 25.67
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Inflammatory mediators and NSAID effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glutathione Transferases and Polymorphisms
- Keywords
- p23, cyclooxygenase-1, prostaglandin E2 synthesis, glutathione-dependent enzymes, arachidonic acid, cytosolic phospholipase A2, lipopolysaccharide, brain, cyclooxygenase-2, tissue homeostasis
- MeSH terms
- Prostaglandin-E Synthases, Amino Acid Sequence, Animals, Brain, Cell Line, Cytosol, Escherichia coli, Cricetinae, HeLa Cells, Humans, Isoenzymes, L Cells, Lipopolysaccharides, Male, Membrane Proteins, Osteoblasts, Prostaglandin-Endoperoxide Synthases, Recombinant Proteins, Dinoprostone, Mutagenesis, Site-Directed, Sequence Alignment, CHO Cells, 3T3 Cells, Rats, Wistar, Sequence Homology, Amino Acid, Intramolecular Oxidoreductases, Amino Acid Substitution, Mice, Rats, Cyclooxygenase 1
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