Involvement of a CrmA-insensitive ICE/Ced-3-like protease in ceramide-induced apoptosis.
Ceramide has emerged as a novel lipid mediator of tumor necrosis factor (TNF)-induced apoptosis. However, the signals involved in this response are unknown. The present study demonstrates that ceramide-induced internucleosomal DNA cleavage is temporally associated with proteolytic cleavage of poly(ADP-ribose) polymerase (PARP) and protein kinase C (PKC) delta. Overexpression of baculovirus protein p35 blocked ceramide-induced DNA fragmentation and proteolytic activity, whereas overexpression of cowpox virus protein CrmA had no effect on these events. By contrast, TNF-induced DNA cleavage and proteolytic activity was inhibited by CrmA as well as p35. These results indicate that ceramide-induced apoptosis involves the activation of a CrmA-insensitive protease that is distinct from that induced by TNF.
Kojima
H
H
Division of Cancer Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Datta
R
R
D017209:Apoptosis / Q000187:drug effects*; D029742:Caenorhabditis elegans Proteins; D020169:Caspases; D002460:Cell Line; D002518:Ceramides / Q000494:pharmacology*; D003546:Cysteine Endopeptidases / Q000502:physiology*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D051745:Protein Kinase C-delta; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D029742:Caenorhabditis elegans Proteins; D002518:Ceramides; D015853:Cysteine Proteinase Inhibitors; D007527:Isoenzymes; D014409:Tumor Necrosis Factor-alpha; D011065:Poly(ADP-ribose) Polymerases; C497258:PRKCD protein, human; D011493:Protein Kinase C; D051745:Protein Kinase C-delta; D020169:Caspases; D003546:Cysteine Endopeptidases; C089223:ced-3 protein, C elegans