Rapid degradation of cyclooxygenase-1 and hematopoietic prostaglandin D synthase through ubiquitin-proteasome system in response to intracellular calcium level

Mol Biol Cell. 2012 Jan;23(1):12-21. doi: 10.1091/mbc.E11-07-0623. Epub 2011 Nov 2.


Cyclooxygenase (COX)-1 and hematopoietic prostaglandin (PG) D synthase (H-PGDS) proteins, which are both involved in the arachidonate cascade, were stable in human megakaryocytic MEG-01 cells. In contrast, once the intracellular calcium level was increased by treatment with a calcium ionophore, both protein levels rapidly decreased with a half-life of less than 30 and 120 min for COX-1 and H-PGDS, respectively. In the presence of a proteasome inhibitor, COX-1 and H-PGDS proteins accumulated within 10 and 30 min, respectively, and concurrently appeared as the high-molecular-mass ubiquitinated proteins within 30 and 60 min, respectively, after an increase in the intracellular calcium level. The ubiquitination of these proteins was also observed when ADP, instead of a calcium ionophore, was used as an inducer to elevate the intracellular calcium level. When the entry of calcium ion into the cells was inhibited by ethylene glycol tetraacetic acid (EGTA), the ubiquitination of COX-1 and H-PGDS was clearly suppressed; and the addition of CaCl(2) to the medium cleared the EGTA-mediated suppression of the ubiquitination. These results indicate that COX-1 and H-PGDS were rapidly ubiquitinated and degraded through the ubiquitin-proteasome system in response to the elevation of the intracellular calcium level.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate / pharmacology
  • Arachidonic Acid / metabolism
  • Calcimycin / pharmacology
  • Calcium Ionophores / pharmacology
  • Calcium Signaling / drug effects*
  • Cell Line
  • Cyclooxygenase 1 / metabolism*
  • Half-Life
  • Humans
  • Intramolecular Oxidoreductases / metabolism*
  • Leupeptins / pharmacology
  • Lipocalins / metabolism*
  • Proteasome Endopeptidase Complex / metabolism*
  • Proteasome Inhibitors
  • Protein Stability
  • Proteolysis
  • Ubiquitinated Proteins / metabolism
  • Ubiquitination


  • Calcium Ionophores
  • Leupeptins
  • Lipocalins
  • Proteasome Inhibitors
  • Ubiquitinated Proteins
  • Arachidonic Acid
  • Calcimycin
  • Adenosine Diphosphate
  • Cyclooxygenase 1
  • PTGS1 protein, human
  • Proteasome Endopeptidase Complex
  • Intramolecular Oxidoreductases
  • prostaglandin R2 D-isomerase
  • benzyloxycarbonylleucyl-leucyl-leucine aldehyde