Ceramide induces apoptosis via CPP32 activation.
Although both ceramide and interleukin-1beta converting enzyme (ICE) family proteases are key molecules during apoptosis, their relationship remains to be elucidated. We report here that cell-permeable ceramide induced cleavage and activation of CPP32, a Ced-3/ICE-like protease, but not ICE. Ceramide-induced apoptosis of Jurkat cells was blocked by the CPP32-specific tetrapeptide inhibitor DEVD-CHO, but not by the ICE inhibitor YVAD-CHO. Furthermore, variant Jurkat cells with defective CPP32 activation were resistant to both anti-Fas- and ceramide-induced apoptosis. These results indicate that CPP32 activation is required for ceramide-induced apoptosis, and suggest sphingomyelin-ceramide pathway functions upstream of CPP32.
The First Department of Internal Medicine, Faculty of Medicine, Tokyo Medical and Dental University, Japan.
N
N
Mizushima
R
R
Koike
H
H
Kohsaka
Y
Y
Kushi
S
S
Handa
H
H
Yagita
N
N
Miyasaka
D017209:Apoptosis / Q000187:drug effects*; D020170:Caspase 1; D053148:Caspase 3; D020169:Caspases; D002518:Ceramides / Q000494:pharmacology; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004792:Enzyme Precursors / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D007700:Kinetics; D009842:Oligopeptides / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology
D002518:Ceramides; D004791:Enzyme Inhibitors; D004792:Enzyme Precursors; C064769:N-acetylsphingosine; D009842:Oligopeptides; D011480:Protease Inhibitors; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases; D020170:Caspase 1; D013110:Sphingosine