Enhancement of CPP32-like activity in the TNF-treated U937 cells by the proteasome inhibitors

Biochem Biophys Res Commun. 1996 Jul 5;224(1):74-9. doi: 10.1006/bbrc.1996.0986.


CPP32, which is most closely related to CED-3 in the apoptotic protease in C. elegance, is activated during apoptosis induced by anti-Fas and TNF. Since processing of CPP32 is important for the activation, we examined the effects of protease inhibitors on CPP32-like activity in the TNF-treated U937 cells. Unexpectedly, proteasome inhibitors (at 5 microM) such as Z-LLnV, Z-LLL, and lactacystin enhanced CPP32-like activity, Ac-DEVD-MCA degrading activity, in the TNF-treated U937 cells in 3 hr, but E64d, cysteine protease inhibitor, did not. These proteasome inhibitors alone did not enhance CPP32-like activity in the untreated U937 cells under the condition used. The proteasome seems to protect the cells from apoptosis by degrading CPP32-like protease or its processing enzyme.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Caspase 3
  • Caspases*
  • Cell Line
  • Cysteine Endopeptidases / metabolism*
  • Cysteine Proteinase Inhibitors / pharmacology*
  • Enzyme Precursors / metabolism
  • Humans
  • Kinetics
  • Multienzyme Complexes / metabolism*
  • Oligopeptides / pharmacology
  • Proteasome Endopeptidase Complex
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / pharmacology*


  • Cysteine Proteinase Inhibitors
  • Enzyme Precursors
  • Multienzyme Complexes
  • Oligopeptides
  • Tumor Necrosis Factor-alpha
  • CASP3 protein, human
  • Caspase 3
  • Caspases
  • Cysteine Endopeptidases
  • Proteasome Endopeptidase Complex