title: Unique and overlapping substrate specificities of caspase-8 and caspase-10.
abstract: Although caspase-8 has an established role as an initiator of death receptor-mediated apoptosis, the function of its closest homolog, caspase-10, is almost completely unknown. To gain a closer insight into the physiological function of caspase-10, we compared the cleavage of known caspase-8 substrates by both initiator caspases. We demonstrate that caspase-10 and -8 have overlapping cleavage preferences for several substrates such as the kinases RIP and PAK2. Interestingly, in other substrates, such as the Bcl-2 protein Bid, we found additional and distinct cleavage sites for both caspases, which might have important consequences for mitochondrial targeting and propagation of the death signal. Caspase-8 and -10 also caused different interchain cleavage patterns of their enzyme precursors. Together, these results suggest that caspase-8 and -10, despite having overlapping functions, also have selective substrate cleavage specificities and might thereby exert nonredundant roles in apoptosis signaling.
authors.affiliation: Institute of Molecular Medicine, Heinrich-Heine-University, Düsseldorf, Germany. ute.fischer@uni-deusseldorf.de
authors.forename: U
authors.initials: U
authors.lastname: Fischer
authors.forename: C
authors.initials: C
authors.lastname: Stroh
authors.forename: K
authors.initials: K
authors.lastname: Schulze-Osthoff
mesh_terms: D000595:Amino Acid Sequence; D017209:Apoptosis; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism; D053455:Caspase 10; D053181:Caspase 8; D020169:Caspases / Q000737:chemistry* / Q000378:metabolism*; D020134:Catalytic Domain; D045744:Cell Line, Tumor; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019169:Jurkat Cells; D008957:Models, Genetic; D008969:Molecular Sequence Data; D011485:Protein Binding; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013379:Substrate Specificity
chemical_list: D051023:BH3 Interacting Domain Death Agonist Protein; C505530:CASP8 protein, human; D053455:Caspase 10; D053181:Caspase 8; D020169:Caspases; C506438:CASP10 protein, human