Cyclooxygenase isozymes and their gene structures and expression.
The cyclooxygenase (COX, prostaglandin endoperoxide synthase) is a key enzyme in prostaglandin biosynthesis. Two isoforms of COX, COX-1 and COX-2, have been identified by molecular biological methods. The amino acid sequence homology between COX-1 and COX-2 is about 60% for the human enzymes. COX-1 is constitutively expressed in most tissues and cells in animal species. The COX-1 promoter region lacks a canonical TATA or CAAT box and is GC-rich. These features are consistent with those of a housekeeping gene. On the other hand, COX-2 is an inducible enzyme and is induced by various cytokines and mitogenic factors. The induction of COX-2 is suppressed by dexamethasone and PGJ2. There are many consensus cis-elements in the 5'-flanking region to regulate the expression of COX-2. Among them, a CRE, an NF-kappaB site, a NF-IL6 motif and an E-box, regulate transcription independently or synergistically. Most of the transcriptional signaling pathways require activation of the mitogen-activated protein kinase (MAPK) cascade. Moreover, MAPK signaling pathways are involved in regulating COX-2 gene expression at the post-transcriptional level.
Tanabe
Tadashi
T
Department of Pharmacology, National Cardiovascular Center Research Institute, Suita, Osaka, Japan. tanabe@jsc.ri.ncvc.go.jp
Tohnai
Norimitsu
N
D000818:Animals; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015971:Gene Expression Regulation, Enzymologic; D005938:Glucocorticoids / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology; D008565:Membrane Proteins; D016328:NF-kappa B / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics* / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid
D005938:Glucocorticoids; D007527:Isoenzymes; D008565:Membrane Proteins; D016328:NF-kappa B; D011956:Receptors, Cell Surface; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases