Reactome | TRIF-mediated programmed cell death

TRIF-mediated programmed cell death

Stable Identifier

R-HSA-2562578

Type

Pathway

Species

Homo sapiens

Compartment

endosome membrane, cytosol

ReviewStatus

5/5

Locations in the PathwayBrowser

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Immune System (Homo sapiens)

- Innate Immune System (Homo sapiens)
  - Toll-like Receptor Cascades (Homo sapiens)
    - Toll Like Receptor 4 (TLR4) Cascade (Homo sapiens)
      - MyD88-independent TLR4 cascade (Homo sapiens)
        
        TRIF (TICAM1)-mediated TLR4 signaling (Homo sapiens)
        
        TRIF-mediated programmed cell death (Homo sapiens)

General

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TLR3 and -4 trigger TRIF-dependent programmed cell death in various human and mouse cells (Kalai M et al. 2002; Han KJ et al. 2004; Kaiser WJ and Offermann MK 2005; Estornes Y et al. 2012; He S et al. 2011). Apoptosis is a prevalent form of programmed cell death and is mediated by the activation of a set of caspases. In addition to apoptosis, TLR3/TLR4 activation induces RIP3-dependent necroptosis. These two programmed cell-death pathways may suppress each other. When the caspase activity is impaired or inhibited, certain cell types switch the apoptotic death program to necroptosis in response to various stimuli (TNF, Fas, viral infection and other stress stimuli) (Kalai M et al. 2002; Weber A et al. 2010; Feoktistova M et al. 2011, Tenev et al 2011).

Literature References

PubMed ID	Title	Journal	Year
22421964	dsRNA induces apoptosis through an atypical death complex associating TLR3 to caspase-8 Pierrot, A, Salaun, B, Lalaoui, N, Jacquemin, G, Micheau, O, Renno, T, Bonnin, M, Vanbervliet, B, Virard, F, Estornes, Y, Lebecque, S, Pachéco, Y, Toscano, F, Mercier-Gouy, P	Cell Death Differ.	2012
15814722	Apoptosis induced by the toll-like receptor adaptor TRIF is dependent on its receptor interacting protein homotypic interaction motif Offermann, MK, Kaiser, WJ	J Immunol	2005
20019748	Proapoptotic signalling through Toll-like receptor-3 involves TRIF-dependent activation of caspase-8 and is under the control of inhibitor of apoptosis proteins in melanoma cells Leverkus, M, Häcker, G, Kirejczyk, Z, Weber, A, Potthoff, S, Besch, R	Cell Death Differ.	2010
21737329	The Ripoptosome, a signaling platform that assembles in response to genotoxic stress and loss of IAPs Zachariou, A, Langlais, C, Darding, M, Tenev, T, Cain, K, Bianchi, K, MacFarlane, M, Lopez, J, Meier, P, Broemer, M, Wallberg, F	Mol. Cell	2011
14739303	Mechanisms of the TRIF-induced interferon-stimulated response element and NF-kappaB activation and apoptosis pathways Zhang, J, Shu, HB, Han, KJ, Bin, LH, Su, X, Xu, LG	J. Biol. Chem.	2004
12181749	Tipping the balance between necrosis and apoptosis in human and murine cells treated with interferon and dsRNA Kalai, M, Van Loo, G, Vandenabeele, P, Burm, W, Meeus, A, Vanden Berghe, T, Saelens, X	Cell Death Differ.	2002
21737330	cIAPs block Ripoptosome formation, a RIP1/caspase-8 containing intracellular cell death complex differentially regulated by cFLIP isoforms Langlais, C, Geserick, P, Kellert, B, Häcker, G, Cain, K, Feoktistova, M, Hupe, M, MacFarlane, M, Leverkus, M, Dimitrova, DP	Mol. Cell	2011