Caveolin-1 interacts with Derlin-1 and promotes ubiquitination and degradation of cyclooxygenase-2 via collaboration with p97 complex

J Biol Chem. 2013 Nov 15;288(46):33462-9. doi: 10.1074/jbc.M113.521799. Epub 2013 Oct 2.


Caveolin-1 (Cav-1) interacts with and mediates protein trafficking and various cellular functions. Derlin-1 is a candidate for the retrotranslocation channel of endoplasmic reticulum proteins. However, little is known about how Derlin-1 mediates glycosylated protein degradation. Here, we identified Cav-1 as a key player in Derlin-1- and p97-mediated cyclooxygenase 2 (COX-2) ubiquitination and degradation. Derlin-1 augmented the interaction of Cav-1 and COX-2 and mediated the degradation of COX-2 in a COX-2 C terminus-dependent manner. Suppression of Cav-1 decreased the ubiquitination of COX-2, and mutation of Asn-594 to Ala to disrupt N-glycosylation at the C terminus of COX-2 reduced the interaction of COX-2 with Cav-1 but not Derlin-1. Moreover, suppression of p97 increased the ubiquitination of COX-2 and up-regulated COX-2 but not COX-1. Cav-1 enhanced the interaction of p97 with Ufd1 and Derlin-1 and collaborated with p97 to interact with COX-2. Cav-1 may be a cofactor in the interaction of Derlin-1 and N-glycosylated COX-2 and may facilitate Derlin-1- and p97 complex-mediated COX-2 ubiquitination, retrotranslocation, and degradation.

Keywords: Caveolin; Caveolin-1; Cyclooxygenase (COX) Pathway; Cyclooxygenase-2; Derlin-1; ER-associated Degradation; Protein Degradation; Ubiquitination; p97.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Vesicular Transport
  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / metabolism*
  • Animals
  • Caveolin 1 / genetics
  • Caveolin 1 / metabolism*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism*
  • HEK293 Cells
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Multiprotein Complexes / genetics
  • Multiprotein Complexes / metabolism*
  • Protein Transport / physiology
  • Proteins / genetics
  • Proteins / metabolism
  • Proteolysis*
  • Ubiquitination / physiology*
  • Valosin Containing Protein


  • Adaptor Proteins, Vesicular Transport
  • CAV1 protein, human
  • Cav1 protein, mouse
  • Caveolin 1
  • Cell Cycle Proteins
  • DERL1 protein, human
  • Intercellular Signaling Peptides and Proteins
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Multiprotein Complexes
  • Proteins
  • UFD1 protein, human
  • Ufd1 protein, mouse
  • derlin-1 protein, mouse
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Adenosine Triphosphatases
  • Valosin Containing Protein