title: Human cell-death-inducing DFF45-like effector C induces apoptosis via caspase-8.
abstract: Human cell-death-inducing DNA-fragmentation-factor (DFF45)-like effector C (CIDEC) is a potent apoptotic inducer. Previous studies have indicated that the Fat-specific protein 27 (Fsp27), a mouse homolog of CIDEC, induces apoptosis via caspase-3, -7, and -9 and triggers the release of cytochrome c from mitochondria, which implies that the mitochondrial pathway is involved in Fsp27-induced apoptosis. In the current study, we found that CIDEC-induced apoptosis was mediated by caspase-8. The caspase inhibitor assay showed that CIDEC-induced apoptosis was dramatically reduced in the presence of the general caspase inhibitor, the caspase-3 inhibitor, and the caspase-8 inhibitor, whereas the caspase-9 inhibitor only weakly inhibited CIDEC-induced apoptosis. These results confirmed that the activation of caspase-3 and caspase-8 were involved in CIDEC-induced apoptosis. Moreover, in caspase-3- or caspase-8-deficient cells, CIDEC-induced apoptosis were dramatically decreased, which demonstrated that CIDEC-induced apoptosis might require the activation of caspase-3 and caspase-8. Because caspase-8 in general is a key effecter of death-receptor pathway and activated by Fas-Associated protein with Death Domain (FADD), we examined whether FADD was involved in CIDEC-induced apoptosis. Our results demonstrated that CIDEC-induced apoptosis was independent of FADD, suggesting that CIDEC-induced apoptosis might be in a death-receptor-independent, caspase-8-dependent manner. It was also found that the region of amino acid 168-200 in carboxyl domain of CIDEC was critical for its crucial pro-apoptotic function.
authors.affiliation: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Tang
authors.forename: Zhen
authors.initials: Z
authors.lastname: Xing
authors.forename: Hong
authors.initials: H
authors.lastname: Tang
authors.forename: Liang
authors.initials: L
authors.lastname: Liang
authors.forename: Mujun
authors.initials: M
authors.lastname: Zhao
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D053181:Caspase 8 / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D053938:DNA Fragmentation; D004789:Enzyme Activation; D053200:Fas-Associated Death Domain Protein / Q000378:metabolism; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; C472088:CIDEC protein, human; D053200:Fas-Associated Death Domain Protein; D011506:Proteins; D053181:Caspase 8