The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.
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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Cites
Prostaglandin Endoperoxide H Synthases (Cyclooxygenases)-1 and −2
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Self-citationRequirement of a 5-lipoxygenase-activating protein for leukotriene synthesis
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Different Intracellular Locations for Prostaglandin Endoperoxide H Synthase-1 and −2
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Glutathione S-Transferases - A Review
Salinas, A. E., & Wong, M. G. (1999) · Current Medicinal Chemistry · doi:10.2174/0929867306666220208213032 · Cited by 556
Functional requirement of p23 and Hsp90 in telomerase complexesPreprint
Holt, S. E., Aisner, D. L., Baur, J. A., Tesmer, V. M., Dy, M., Ouellette, M., Trager, J. B., Morin, G. B., Toft, D. O., Shay, J. W., et al. (1999) · Genes & Development · doi:10.1101/gad.13.7.817 · Cited by 543
The Functions of Five Distinct Mammalian Phospholipase A2s in Regulating Arachidonic Acid Release
Murakami, M., Shimbara, S., Kambe, T., Kuwata, H., Winstead, M. V., Tischfield, J. A., & Kudo, I. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.23.14411 · Cited by 366
Self-citationJakobsson, P., Morgenstern, R., Mancini, J. A., Ford‐Hutchinson, A. W., & Persson, B. (1999) · Protein Science · doi:10.1110/ps.8.3.689 · Cited by 366
Murakami, M., Kambe, T., Shimbara, S., & Kudo, I. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.5.3103 · Cited by 348
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Prostaglandins and Inflammation
Ricciotti, E., & FitzGerald, G. A. (2011) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.110.207449 · Cited by 4,035
Murakami, M., Naraba, H., Tanioka, T., Semmyo, N., Nakatani, Y., Kojima, F., Ikeda, T., Fueki, M., Ueno, A., Oh-ishi, S., et al. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m003505200 · Cited by 964
Self-citationPharmacokinetics and pharmacodynamics of systemically administered glucocorticoids.
Czock, D., Keller, F., Rasche, F. M., & H??ussler, U. (2005) · Clinical Pharmacokinetics · doi:10.2165/00003088-200544010-00003 · Cited by 886
Prostaglandin E2 synthesis and secretion: The role of PGE2 synthases
Park, J. Y., Pillinger, M. H., & Abramson, S. B. (2006) · Clinical Immunology · doi:10.1016/j.clim.2006.01.016 · Cited by 793
Why there are two cyclooxygenase isozymes
Smith, W. L., & Langenbach, R. J. (2001) · Journal of Clinical Investigation · doi:10.1172/jci13271 · Cited by 612
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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