Enhancement of CPP32-like activity in the TNF-treated U937 cells by the proteasome inhibitors.
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.
Fujita
E
E
Division of Development and Differentiation, NCNP, Tokyo, Japan.
Mukasa
T
T
Tsukahara
T
T
Arahata
K
K
Omura
S
S
Momoi
T
T
D053148:Caspase 3; D020169:Caspases; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D004792:Enzyme Precursors / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D009097:Multienzyme Complexes / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D015853:Cysteine Proteinase Inhibitors; D004792:Enzyme Precursors; D009097:Multienzyme Complexes; D009842:Oligopeptides; D014409:Tumor Necrosis Factor-alpha; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex