title: prICE: a downstream target for ceramide-induced apoptosis and for the inhibitory action of Bcl-2.
abstract: 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.
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Smyth
authors.forename: D K
authors.initials: DK
authors.lastname: Perry
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: G G
authors.initials: GG
authors.lastname: Poirier
authors.forename: Y A
authors.initials: YA
authors.lastname: Hannun
authors.forename: L M
authors.initials: LM
authors.lastname: Obeid
mesh_terms: 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
chemical_list: 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