The death effector domains (DEDs) of the molluscum contagiosum virus MC159 v-FLIP protein are not functionally interchangeable with each other or with the DEDs of caspase-8.
The molluscum contagiosum virus (MCV) MC159 protein contains two death effector domains (DEDs) that bind to the DEDs of caspase-8 and FADD and inhibit apoptosis. We constructed MC159 truncation mutants and found that the amino-terminal region before the first DED and nearly all the carboxyl terminus after the second DED were dispensable for the antiapoptotic activity of MC159. We also engineered tandem repeats of two identical MC159 DEDs, MC159 DEDs in the reverse orientation, and MC159-caspase-8 chimeras in which a DED of MC159 was replaced with the corresponding DED of caspase-8. Each of these constructs bound to caspase-8, but was unable to bind to FADD or block apoptosis. In addition, we constructed mutants containing only a single DED of MC159. These mutants bound to both FADD and caspase-8, but could not block apoptosis or the formation of death effector filaments. Thus, the DEDs of MC159 are not functionally interchangeable with each other or with those of caspase-8.
D048868:Adaptor Proteins, Signal Transducing; D017209:Apoptosis; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000502:physiology; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000737:chemistry* / Q000502:physiology; D053200:Fas-Associated Death Domain Protein; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D019169:Jurkat Cells; D008977:Molluscum contagiosum virus / Q000737:chemistry* / Q000502:physiology; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D014764:Viral Proteins / Q000737:chemistry* / Q000502:physiology; D019014:fas Receptor / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D002352:Carrier Proteins; C505533:FADD protein, human; D053200:Fas-Associated Death Domain Protein; D047908:Intracellular Signaling Peptides and Proteins; D014409:Tumor Necrosis Factor-alpha; D014764:Viral Proteins; D019014:fas Receptor; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases