prICE: a downstream target for ceramide-induced apoptosis and for the inhibitory action of Bcl-2.
The novel lipid second messenger, ceramide, specifically induced poly(ADP-ribose) polymerase cleavage through activation of the protease prICE. Over-expression of Bcl-2 inhibited ceramide-induced poly(ADP-ribose) polymerase proteolysis and protected cells from ceramide-induced death. These data provide the first insight into the mechanism by which ceramide mediates apoptosis and suggest a mechanism by which Bel-2 protects from cell death.
Smyth
M J
MJ
Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
Perry
D K
DK
Zhang
J
J
Poirier
G G
GG
Hannun
Y A
YA
Obeid
L M
LM
D017209:Apoptosis / Q000187:drug effects*; D020170:Caspase 1; D002460:Cell Line; D002518:Ceramides / Q000494:pharmacology*; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2; D015290:Second Messenger Systems; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D002518:Ceramides; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D014409:Tumor Necrosis Factor-alpha; D011065:Poly(ADP-ribose) Polymerases; D011505:Protein-Tyrosine Kinases; D003546:Cysteine Endopeptidases; D020170:Caspase 1