Good COP1 or bad COP1? In vivo veritas

J Clin Invest. 2011 Apr;121(4):1263-5. doi: 10.1172/JCI57080. Epub 2011 Mar 14.


The evolutionarily conserved protein COP1 has been shown to operate as an E3 ubiquitin ligase complex, and a number of putative substrates have been identified, including the c-JUN oncoprotein and p53 tumor suppressor protein. New work by Migliorini and colleagues described in the current issue of JCI demonstrates that COP1 acts as a tumor suppressor in vivo and does so, at least in part, by promoting the destruction of c-JUN. These findings challenge the view that COP1 regulates p53 stability and call into question the wisdom of developing COP1 inhibitors as potential anticancer agents.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Comment

MeSH terms

  • Animals
  • Enzyme Stability
  • Humans
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Mice
  • Mice, Mutant Strains
  • Models, Biological
  • Neoplasms / etiology
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Tumor Suppressor Protein p53 / metabolism
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism*


  • Nuclear Proteins
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
  • COP1 protein, mouse
  • Ubiquitin-Protein Ligases
  • JNK Mitogen-Activated Protein Kinases