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  • Title: Ceramide induces apoptosis via CPP32 activation.
    Author: Mizushima N, Koike R, Kohsaka H, Kushi Y, Handa S, Yagita H, Miyasaka N.
    Journal: FEBS Lett; 1996 Oct 21; 395(2-3):267-71. PubMed ID: 8898109.
    Abstract:
    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.
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