title: Cleavage of human cytosolic phospholipase A2 by caspase-1 (ICE) and caspase-8 (FLICE).
abstract: The activation of caspases appears to play a key role in programmed cell death. An increasing number of substrates have been identified that are cleaved by caspases. In a previous study, we have reported that human cPLA2 is proteolytically inactivated during apoptosis through cleavage by a caspase-3-like activity. Here, we show that in cotransfection experiments the previously identified cleavage site at Asp522 can be used by a wide variety of caspases belonging to different subfamilies. The formation of additional fragments implied differences in cleavage site usage between the closely related caspases-3 and -7. A different cleavage pattern of cPLA2 was observed with caspase-1. Mutational analysis identified the caspase-1 cleavage site at Asp459 within the sequence YQSD/N. Most interestingly, we found that even caspase-8, an upstream component of the proposed caspase cascade, cleaves cPLA2 in vitro. The presence of multiple cleavage sites warrants proteolysis and inactivation of the proinflammatory cPLA2 during apoptosis.
authors.affiliation: Institut für Immunologie, Christian-Albrechts-Universität Kiel, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Lüschen
authors.forename: S
authors.initials: S
authors.lastname: Ussat
authors.forename: M
authors.initials: M
authors.lastname: Krönke
authors.forename: S
authors.initials: S
authors.lastname: Adam-Klages
mesh_terms: D017209:Apoptosis / Q000235:genetics; D020170:Caspase 1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D003600:Cytosol / Q000201:enzymology*; D004789:Enzyme Activation / Q000235:genetics; D006801:Humans; D006868:Hydrolysis; D007668:Kidney; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection
chemical_list: D011994:Recombinant Proteins; D010741:Phospholipases A; D054467:Phospholipases A2; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases; D020170:Caspase 1