Cyclooxygenase isozymes and their gene structures and expression

Prostaglandins Other Lipid Mediat. 2002 Aug;68-69:95-114. doi: 10.1016/s0090-6980(02)00024-2.

Abstract

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Gene Expression Regulation, Enzymologic
  • Glucocorticoids / metabolism
  • Humans
  • Isoenzymes / genetics*
  • Isoenzymes / metabolism*
  • MAP Kinase Signaling System / physiology
  • Membrane Proteins
  • NF-kappa B / metabolism
  • Prostaglandin-Endoperoxide Synthases / genetics*
  • Prostaglandin-Endoperoxide Synthases / metabolism*
  • Receptors, Cell Surface / metabolism
  • Regulatory Sequences, Nucleic Acid

Substances

  • Glucocorticoids
  • Isoenzymes
  • Membrane Proteins
  • NF-kappa B
  • Receptors, Cell Surface
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • PTGS1 protein, human
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases