Title: Prostaglandin E Synthase: A Novel Drug Target for Inflammation and Cancer
Volume: 12
Issue: 8
Author(s): Makoto Murakami and Ichiro Kudo
Affiliation:
Keywords:
Prostaglandin E2, prostaglandin E synthase, Cyclooxygenase, Inflammation, Cancer, Knockout Mouse
Abstract: Prostaglandin E synthase (PGES), which converts cyclooxygenase (COX)-derived prostaglandin (PG) H2 to PGE2, occurs in multiple forms with distinct enzymatic properties, modes of expression, cellular and subcellular localizations and intracellular functions. Two of them are membrane-bound enzymes and have been designated as mPGES-1 and mPGES-2. mPGES-1 is a perinuclear protein belonging to the MAPEG (for membrane-associated proteins involved in eicosanoid and GSH metabolism) family. This enzyme is markedly induced by proinflammatory stimuli, is down-regulated by anti-inflammatory glucocorticoids, and is functionally coupled with cyclooxygenase (COX)-2 in marked preference to COX-1. mPGES-2 is synthesized as a Golgi membrane-associated protein, and the proteolytic removal of the N-terminal hydrophobic domain leads to the formation of a mature cytosolic enzyme. This enzyme is rather constitutively expressed in various cells and tissues and is functionally coupled with both COX-1 and COX-2. Cytosolic PGES (cPGES) is constitutively expressed in a wide variety of cells and is functionally linked to COX-1 to promote immediate PGE2 production. This review highlights the latest understanding of the expression, regulation and functions of these three PGES enzymes. In particular, recent gene targeting studies of mPGES-1 have revealed that this enzyme represents a novel target for anti-inflammatory and anti-cancer drugs.
