Recruitment of TRADD, FADD, and caspase 8 to double-stranded RNA-triggered death inducing signaling complexes (dsRNA-DISCs).
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.
Iordanov
M S
MS
Department of Cell and Developmental Biology, Oregon Health & Science University, Portland, Oregon 97239, USA.
Kirsch
J D
JD
Ryabinina
O P
OP
Wong
J
J
Spitz
P N
PN
Korcheva
V B
VB
Thorburn
A
A
Magun
B E
BE
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*
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