TNFR1-induced proapoptotic signaling

Stable Identifier
R-HSA-5357786
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Pathway
Species
Homo sapiens
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Activation of tumor necrosis factor receptor 1 (TNFR1) can trigger multiple signal transduction pathways to induce cell survival or cell death (Ward C et al. 1999; Micheau O and Tschopp J 2003; Widera D et al. 2006). While pro-survival signaling is initiated and regulated via the activated TNFR1 receptor complex at the cell membrane, cell death signals are induced upon the release of TRADD:TRAF2:RIP1 complex from the membrane to the cytosol where it forms death-inducing signaling complex (DISC) (Micheau O and Tschopp J 2003; Schneider-Brachert W et al. 2004). Upon apoptotic stimulation procaspase-8 or 10 is recruited into the DISC, and close proximity promotes the dimerization, autocatalytic processing, and activation of the initiator caspase-8 (and/or caspase-10) (Wang J et al. 2001; Boatright KM and Salvesen GS 2003). The initiator caspases then process and activate the downstream effector caspases such as caspase-3 in a proteolytic cascade (Stennicke HR et al. 1998). The effector caspases in turn cleave many diverse substrates, ultimately inducing cell death.

Literature References
PubMed ID Title Journal Year
12752666 Caspase-activation pathways in apoptosis and immunity

Creagh, EM, Conroy, H, Martin, SJ

Immunol Rev 2003
12505355 History of the events leading to the formulation of the apoptosis concept

Kerr, JF

Toxicology 2002
12887920 Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes

Micheau, O, Tschopp, J

Cell 2003
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