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.