title: Recruitment of TRADD, FADD, and caspase 8 to double-stranded RNA-triggered death inducing signaling complexes (dsRNA-DISCs).
abstract: Rapid elimination of virus-infected cells by apoptosis is an efficient anti-viral strategy. Double-stranded RNA (dsRNA), a viral product, is potently and rapidly apoptogenic in susceptible cells. Caspase 8 plays an important role in the dsRNA-induced apoptosis; however, the mechanisms of caspase 8 activation in response to dsRNA are unknown. We demonstrate here that, in HeLa cells, the dsRNA-triggered activation of caspase 8 is independent of ongoing proteins synthesis (and is, therefore, independent of changes in pro- and anti-apoptotic gene expression) and involves the formation of multiprotein dsRNA-triggered death inducing signaling complexes (dsRNA-DISCs). DsRNA-DISCs contain FADD, TRADD, and caspase 8; however, several experimental approaches suggest that death ligands and death receptors (such as Fas/Apo1 and DR4/Apo2) are not involved in the formation of dsRNA-DISCs.
authors.affiliation: Department of Cell and Developmental Biology, Oregon Health & Science University, Portland, Oregon 97239, USA.
authors.forename: M S
authors.initials: MS
authors.lastname: Iordanov
authors.forename: J D
authors.initials: JD
authors.lastname: Kirsch
authors.forename: O P
authors.initials: OP
authors.lastname: Ryabinina
authors.forename: J
authors.initials: J
authors.lastname: Wong
authors.forename: P N
authors.initials: PN
authors.lastname: Spitz
authors.forename: V B
authors.initials: VB
authors.lastname: Korcheva
authors.forename: A
authors.initials: A
authors.lastname: Thorburn
authors.forename: B E
authors.initials: BE
authors.lastname: Magun
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D017209:Apoptosis; D053181:Caspase 8; D020169:Caspases / Q000378:metabolism*; D053418:Death Domain Receptor Signaling Adaptor Proteins; D053200:Fas-Associated Death Domain Protein; D006367:HeLa Cells; D006801:Humans; D012330:RNA, Double-Stranded / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D015398:Signal Transduction; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D053418:Death Domain Receptor Signaling Adaptor Proteins; C505533:FADD protein, human; D053200:Fas-Associated Death Domain Protein; D012330:RNA, Double-Stranded; D018124:Receptors, Tumor Necrosis Factor; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; C505530:CASP8 protein, human; D053181:Caspase 8; D020169:Caspases