TRIF-mediated programmed cell death

Stable Identifier
R-HSA-2562578
Type
Pathway
Species
Homo sapiens
Compartment
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Summation

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
15814722 Apoptosis induced by the toll-like receptor adaptor TRIF is dependent on its receptor interacting protein homotypic interaction motif

Kaiser, WJ, Offermann, MK

J Immunol 2005
22421964 dsRNA induces apoptosis through an atypical death complex associating TLR3 to caspase-8

Estornes, Y, Toscano, F, Virard, F, Jacquemin, G, Pierrot, A, Vanbervliet, B, Bonnin, M, Lalaoui, N, Mercier-Gouy, P, Pachéco, Y, Salaun, B, Renno, T, Micheau, O, Lebecque, S

Cell Death Differ. 2012
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

Weber, A, Kirejczyk, Z, Besch, R, Potthoff, S, Leverkus, M, Häcker, G

Cell Death Differ. 2010
21737329 The Ripoptosome, a signaling platform that assembles in response to genotoxic stress and loss of IAPs

Tenev, T, Bianchi, K, Darding, M, Broemer, M, Langlais, C, Wallberg, F, Zachariou, A, Lopez, J, MacFarlane, M, Cain, K, Meier, P

Mol. Cell 2011
14739303 Mechanisms of the TRIF-induced interferon-stimulated response element and NF-kappaB activation and apoptosis pathways

Han, KJ, Su, X, Xu, LG, Bin, LH, Zhang, J, Shu, HB

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, Vanden Berghe, T, Meeus, A, Burm, W, Saelens, X, Vandenabeele, P

Cell Death Differ. 2002
21737330 cIAPs block Ripoptosome formation, a RIP1/caspase-8 containing intracellular cell death complex differentially regulated by cFLIP isoforms

Feoktistova, M, Geserick, P, Kellert, B, Dimitrova, DP, Langlais, C, Hupe, M, Cain, K, MacFarlane, M, Häcker, G, Leverkus, M

Mol. Cell 2011
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