Regulation of intracellular cyclooxygenase levels by gene transcription and protein degradation

Prog Lipid Res. 2007 Mar;46(2):108-25. doi: 10.1016/j.plipres.2007.01.001. Epub 2007 Jan 18.


Cyclooxygenases-1 and -2 (COX-1 and -2) catalyze the committed step in prostaglandin formation. Each isozyme subserves different biological functions. This is, at least in part, a consequence of differences in patterns of COX-1 and COX-2 expression. COX-1 is induced during development, and COX-1 mRNA and COX-1 protein are very stable. These latter properties can explain why COX-1 protein levels usually remain constant in those cells that express this isozyme. COX-2 is usually expressed inducibly in association with cell replication or differentiation. Both COX-2 mRNA and COX-2 protein have short half-lives relative to those of COX-1. Therefore, COX-2 protein is typically present for only a few hours after its synthesis. Here we review and develop the concepts that (a) COX-2 gene transcription can involve at least six different cis-acting promoter elements interacting with trans-acting factors generated by multiple, different signaling pathways, (b) the relative contribution of each cis-acting COX-2 promoter element depends on the cell type, the stimulus and the time following the stimulus and (c) a unique 27 amino acid instability element located just upstream of the C-terminus of COX-2 targets this isoform to the ER-associated degradation system and proteolysis by the cytosolic 26S proteasome.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Cyclooxygenase 1 / genetics*
  • Cyclooxygenase 1 / metabolism*
  • Cyclooxygenase 2 / genetics*
  • Cyclooxygenase 2 / metabolism*
  • Gene Expression Regulation, Enzymologic*
  • Humans
  • Transcription, Genetic / genetics*


  • Cyclooxygenase 1
  • Cyclooxygenase 2