MEKK1 mediates the ubiquitination and degradation of c-Jun in response to osmotic stress

Mol Cell Biol. 2007 Jan;27(2):510-7. doi: 10.1128/MCB.01355-06. Epub 2006 Nov 13.


c-Jun, a major transcription factor in the activating protein 1 family of regulatory proteins, is activated by many physiologic and pathological stimuli. We show here that c-Jun was downregulated in response to osmotic stress via ubiquitination-dependent degradation by the PHD/RING finger domain of MEKK1, which exhibited E3 ubiquitin ligase activity toward c-Jun in vitro and in vivo. The reduced c-Jun protein level resulting from exogenous expression of wild-type MEKK1 and the opposite effect induced by expression of a MEKK1 PHD/RING finger domain mutant were consistent with a higher level of c-Jun protein in MEKK1(-/-) cells than in corresponding wild-type cells. The deficiency of MEKK1 blocked posttranslational downregulation of c-Jun in response to osmotic stress. Furthermore, apoptosis induced by osmotic stress was suppressed by overexpression of c-Jun, indicating that the downregulation of c-Jun promotes apoptosis.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis*
  • Cell Line
  • Down-Regulation*
  • Humans
  • MAP Kinase Kinase Kinase 1 / genetics
  • MAP Kinase Kinase Kinase 1 / physiology*
  • Mice
  • Mitogen-Activated Protein Kinase 8 / metabolism
  • Mutation
  • Osmotic Pressure
  • Proteasome Endopeptidase Complex / physiology
  • Protein Structure, Tertiary
  • Proto-Oncogene Proteins c-jun / genetics
  • Proto-Oncogene Proteins c-jun / metabolism*
  • Rats
  • Ubiquitin-Protein Ligases / metabolism*


  • Proto-Oncogene Proteins c-jun
  • Ubiquitin-Protein Ligases
  • Mitogen-Activated Protein Kinase 8
  • MAP Kinase Kinase Kinase 1
  • Proteasome Endopeptidase Complex