Skip to main content
Log in

Recruitment of TRADD, FADD, and caspase 8 to double-stranded RNA-triggered death inducing signaling complexes (dsRNA-DISCs)

  • Published:
Apoptosis Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Jacobs BL, Langland JO. When two strands are better than one: The mediators and modulators of the cellular responses to double-stranded RNA. Virology 1996; 219: 339–349.

    Google Scholar 

  2. Balachandran S, Kim CN, Yeh WC, Mak TW, Bhalla K, Barber GN. Activation of the dsRNA-dependent protein kinase, PKR, induces apoptosis through FADD-mediated death signaling. Embo J 1998; 17: 6888–6902.

    Google Scholar 

  3. Iordanov MS, Ryabinina OP, Schneider P, Magun BE. Two Mechanisms of Caspase 9 Processing in Double-Stranded RNA- and Virus-Triggered Apoptosis. Apoptosis 10: 153–166

  4. Morgan MJ, Thorburn J, Thomas L, Maxwell T, Brothman AR, Thorburn A. An apoptosis signaling pathway induced by the death domain of FADD selectively kills normal but not cancerous prostate epithelial cells. Cell Death Differ 2001; 8: 696–705.

    Google Scholar 

  5. Cohen GM. Caspases: The executioners of apoptosis. Biochem J 1997; 326(Pt 1): 1–16.

    Google Scholar 

  6. Boldin MP, Goncharov TM, Goltsev YV, Wallach D. Involvement of MACH, a novel MORT1/FADD-interacting protease, in Fas/APO-1-and TNF receptor-induced cell death. Cell 1996; 85: 803–815.

    Google Scholar 

  7. Iordanov MS, Pribnow D, Magun JL, et al. Ribotoxic stress response: Activation of the stress-activated protein kinase JNK1 by inhibitors of the peptidyl transferase reaction and by sequence-specific RNA damage to the alpha-sarcin/ricin loop in the 28S rRNA. Mol Cell Biol 1997; 17: 3373–3381.

    Google Scholar 

  8. Kenworthy A. Peering inside lipid rafts and caveolae. Trends Biochem Sci 2002; 27: 435–437.

    Google Scholar 

  9. Holler N, Tardivel A, Kovacsovics-Bankowski M, et al. Two adjacent trimeric Fas ligands are required for Fas signaling and formation of a death-inducing signaling complex. Mol Cell Biol 2003; 23: 1428–1440.

    Google Scholar 

  10. Micheau O, Tschopp J. Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes. Cell 2003; 114: 181–190.

    Google Scholar 

  11. Locksley RM, Killeen N, Lenardo MJ. The TNF and TNF receptor superfamilies: Integrating mammalian biology. Cell 2001; 104: 487–501.

    Article  CAS  PubMed  Google Scholar 

  12. Chu WM, Ostertag D, Li ZW, et al. JNK2 and IKKbeta are required for activating the innate response to viral infection. Immunity 1999; 11: 721–731.

    CAS  PubMed  Google Scholar 

  13. Iordanov MS, Paranjape JM, Zhou A, et al. Activation of p38 mitogen-activated protein kinase and c-Jun NH(2)-terminal kinase by double-stranded RNA and encephalomyocarditis virus: Involvement of RNase L, protein kinase R, and alternative pathways. Mol Cell Biol 2000; 20: 617– 627.

    Google Scholar 

  14. Iordanov MS, Wong J, Bell JC, Magun BE. Activation of NF-κB by double-stranded RNA (dsRNA) in the absence of protein kinase R and RNase L demonstrates the existence of two separate dsRNA-triggered antiviral programs. Mol Cell Biol 2001; 21: 61–72.

    Google Scholar 

  15. Kalai M, Van Loo G, Vanden Berghe T, et al. Tipping the balance between necrosis and apoptosis in human and murine cells treated with interferon and dsRNA. Cell Death Differ 2002; 9: 981–994.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to B. E. Magun.

Additional information

Deceased

Rights and permissions

Reprints and permissions

About this article

Cite this article

Iordanov, M.S., Kirsch, J.D., Ryabinina, O.P. et al. Recruitment of TRADD, FADD, and caspase 8 to double-stranded RNA-triggered death inducing signaling complexes (dsRNA-DISCs). Apoptosis 10, 167–176 (2005). https://doi.org/10.1007/s10495-005-6071-x

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10495-005-6071-x

Keywords:

Navigation