MPGES-1 explained

Microsomal prostaglandin E synthase-1 (mPGES-1)^{[1] [2]} or Prostaglandin E synthase is an enzyme that in humans is encoded by the PTGES gene.^{[3] [4] [5]}

The protein encoded by this gene is a glutathione-dependent prostaglandin E synthase. The expression of this gene has been shown to be induced by proinflammatory cytokine interleukin 1 beta (IL1B). Its expression can also be induced by tumor suppressor protein TP53, and may be involved in TP53-induced apoptosis.

Knockout studies in mice suggest that this gene may contribute to the pathogenesis of collagen-induced arthritis and mediate acute pain during inflammatory responses.

See also

• Prostaglandin E synthase

Further reading

• Bastien L . Cloning, functional expression, and characterization of the human prostaglandin E2 receptor EP2 subtype . J. Biol. Chem. . 269 . 16 . 11873–7 . 1994 . 8163486 . vanc. Sawyer N . Grygorczyk R . 3 . Metters . KM . Adam . M . 10.1016/S0021-9258(17)32654-6 . free .
• Wu T, Wu H, Wang J, Wang J . Expression and cellular localization of cyclooxygenases and prostaglandin E synthases in the hemorrhagic brain. . J Neuroinflammation . 8 . 22 . 2011 . 21385433 . 10.1186/1742-2094-8-22 . 3062590 . free .
• Funk CD . Cloning and expression of a cDNA for the human prostaglandin E receptor EP1 subtype . J. Biol. Chem. . 268 . 35 . 26767–72 . 1994 . 8253813 . vanc. Furci L . FitzGerald GA . 3 . Grygorczyk . R . Rochette . C . Bayne . MA . Abramovitz . M . Adam . M . Metters . KM . 10.1016/S0021-9258(19)74379-8 . free .
• Giacomini E . Increased PGE2 production mediates the in vitro inhibitory effect of the human immunodeficiency virus P24 immunosuppressive heptapeptide Ch7 . Scand. J. Immunol. . 48 . 3 . 248–53 . 1998 . 9743208 . 10.1046/j.1365-3083.1998.00389.x . vanc. Giordani L . di Modugno F . 3 . Chersi . Luzzati . A . AL . 20332912 .
• Jakobsson PJ, Thorén S, Morgenstern R, Samuelsson B . Identification of human prostaglandin E synthase: a microsomal, glutathione-dependent, inducible enzyme, constituting a potential novel drug target . Proc. Natl. Acad. Sci. U.S.A. . 96 . 13 . 7220–5 . 1999 . 10377395 . 10.1073/pnas.96.13.7220 . 22058 . 1999PNAS...96.7220J . free .
• Forsberg L . Human glutathione dependent prostaglandin E synthase: gene structure and regulation . FEBS Lett. . 471 . 1 . 78–82 . 2000 . 10760517 . 10.1016/S0014-5793(00)01367-3 . vanc. Leeb L . Thorén S . 3 . Morgenstern . R . Jakobsson . P . 10901322 .
• Han R, Smith TJ . Cytoplasmic prostaglandin E2 synthase is dominantly expressed in cultured KAT-50 thyrocytes, cells that express constitutive prostaglandin-endoperoxide H synthase-2. Basis for low protaglandin E2 production . J. Biol. Chem. . 277 . 39 . 36897–903 . 2002 . 12145315 . 10.1074/jbc.M206949200 . free .
• Giannoulias D . Expression of prostaglandin I(2) synthase, but not prostaglandin E synthase, changes in myometrium of women at term pregnancy . J. Clin. Endocrinol. Metab. . 87 . 11 . 5274–82 . 2002 . 12414902 . 10.1210/jc.2002-020521 . vanc. Alfaidy N . Holloway AC . 3 . Gibb . W . Sun . M . Lye . SJ . Challis . JR . free .
• Ouellet M . Purification and characterization of recombinant microsomal prostaglandin E synthase-1 . Protein Expr. Purif. . 26 . 3 . 489–95 . 2003 . 12460774 . 10.1016/S1046-5928(02)00566-1 . vanc. Falgueyret JP . Ear PH . 3 . Pen . A . Mancini . JA . Riendeau . D . Percival . MD .
• Strausberg RL . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . vanc. Feingold EA . Grouse LH . 3 . Derge . JG . Klausner . RD . Collins . FS . Wagner . L . Shenmen . CM . Schuler . GD . 2002PNAS...9916899M . free .
• Uracz W, Uracz D, Olszanecki R, Gryglewski RJ . Interleukin 1beta induces functional prostaglandin E synthase in cultured human umbilical vein endothelial cells . J. Physiol. Pharmacol. . 53 . 4 Pt 1 . 643–54 . 2003 . 12512699 .
• Meadows JW, Eis AL, Brockman DE, Myatt L . Expression and localization of prostaglandin E synthase isoforms in human fetal membranes in term and preterm labor . J. Clin. Endocrinol. Metab. . 88 . 1 . 433–9 . 2003 . 12519887 . 10.1210/jc.2002-021061 . free .
• Kamei D . Potential role of microsomal prostaglandin E synthase-1 in tumorigenesis . J. Biol. Chem. . 278 . 21 . 19396–405 . 2003 . 12626523 . 10.1074/jbc.M213290200 . vanc. Murakami M . Nakatani Y . 3 . Ishikawa . Y . Ishii . T . Kudo . I . free.
• Book: Jakobsson PJ, Thorén S, Morgenstern R, Samuelsson B . Characterization of Microsomal, Glutathione Dependent Prostaglandin e Synthase . Eicosanoids and Other Bioactive Lipids in Cancer, Inflammation, and Radiation Injury, 5 . 507 . 287–91 . 2003 . 12664599 . 10.1007/978-1-4615-0193-0_44 . Advances in Experimental Medicine and Biology . 978-0-306-47283-1 .
• Thorén S . Human microsomal prostaglandin E synthase-1: purification, functional characterization, and projection structure determination . J. Biol. Chem. . 278 . 25 . 22199–209 . 2003 . 12672824 . 10.1074/jbc.M303227200 . vanc. Weinander R . Saha S . 3 . Jegerschöld . C . Pettersson . PL . Samuelsson . B . Hebert . H . Hamberg . M . Morgenstern . R . free .
• Alfaidy N, Sun M, Challis JR, Gibb W . Expression of membrane prostaglandin E synthase in human placenta and fetal membranes and effect of labor . Endocrine . 20 . 3 . 219–25 . 2003 . 12721500 . 10.1385/ENDO:20:3:219 . 9590845 .
• Ekström L . Basal expression of the human MAPEG members microsomal glutathione transferase 1 and prostaglandin E synthase genes is mediated by Sp1 and Sp3 . Biochim. Biophys. Acta . 1627 . 2–3 . 79–84 . 2003 . 12818425 . 10.1016/S0167-4781(03)00077-0. vanc. Lyrenäs L . Jakobsson PJ . 3 . Morgenstern . R . Kelner . MJ .
• Murakami M . Cellular prostaglandin E2 production by membrane-bound prostaglandin E synthase-2 via both cyclooxygenases-1 and -2 . J. Biol. Chem. . 278 . 39 . 37937–47 . 2003 . 12835322 . 10.1074/jbc.M305108200 . vanc. Nakashima K . Kamei D . 3 . Masuda . S . Ishikawa . Y . Ishii . T . Ohmiya . Y . Watanabe . K . Kudo . I . free .
• Trebino CE . Impaired inflammatory and pain responses in mice lacking an inducible prostaglandin E synthase . Proc. Natl. Acad. Sci. U.S.A. . 100 . 15 . 9044–9 . 2003 . 12835414 . 10.1073/pnas.1332766100 . 166435 . vanc. Stock JL . Gibbons CP . 3 . Naiman . BM . Wachtmann . TS . Umland . JP . Pandher . K . Lapointe . JM . Saha . S . 2003PNAS..100.9044T . free .

Notes and References

1. Jakobsson PJ, Thorén S, Morgenstern R, et al. . Identification of human prostaglandin E synthase: a microsomal glutathione-dependent, inducible enzyme, constituting a potential novel drug target. . Proc Natl Acad Sci USA . 96 . 13. 7220–7225 . 1989 . 10377395 . 22058. 10.1073/pnas.96.13.7220 . 1999PNAS...96.7220J . free .
2. Hui-Hua Chang . Emmanuelle J Meuillet . Identification and development of mPGES-1 inhibitors: where we are at? . Future Med Chem . 3 . 15 . 1909–1934 . 2011 . 22023034. 3232027 . 10.4155/fmc.11.136 .
3. Polyak K, Xia Y, Zweier JL, Kinzler KW, Vogelstein B . A model for p53-induced apoptosis . Nature . 389 . 6648 . 300–5 . Sep 1997 . 9305847 . 10.1038/38525 . 1997Natur.389..300P . 4429638 .
4. Jakobsson PJ, Morgenstern R, Mancini J, Ford-Hutchinson A, Persson B . Common structural features of MAPEG -- a widespread superfamily of membrane-associated proteins with highly divergent functions in eicosanoid and glutathione metabolism . Protein Sci . 8 . 3 . 689–92 . May 1999 . 10091672 . 2144274 . 10.1110/ps.8.3.689 .
5. Web site: Entrez Gene: PTGES prostaglandin E synthase.