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Details on Person Tumor necrosis factor α (TNF-α)-induced apoptosis is regulat...
| Class:Id | Summation:179240 |
|---|---|
| _displayName | Tumor necrosis factor α (TNF-α)-induced apoptosis is regulat... |
| _timestamp | 2023-02-20 03:45:54 |
| created | [InstanceEdit:179407] Gopinathrao, G, 2006-04-27 13:13:48 |
| literatureReference | [LiteratureReference:140979] Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes [LiteratureReference:9825249] Cloaked in ubiquitin, a killer hides in plain sight: the molecular regulation of RIPK1 [LiteratureReference:1267800] Inducible dimerization and inducible cleavage reveal a requirement for both processes in caspase-8 activation [LiteratureReference:1267836] Structural and biochemical studies on procaspase-8: new insights on initiator caspase activation [LiteratureReference:9687055] Mutations that prevent caspase cleavage of RIPK1 cause autoinflammatory disease [LiteratureReference:9687059] Cleavage of RIPK1 by caspase-8 is crucial for limiting apoptosis and necroptosis [LiteratureReference:5357755] Loss of caspase-8 expression in highly malignant human neuroblastoma cells correlates with resistance to tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis [LiteratureReference:9698704] Activation of necroptosis in multiple sclerosis [LiteratureReference:9796364] Necroptosis and RIPK1-mediated neuroinflammation in CNS diseases [LiteratureReference:9823770] Linear ubiquitination is involved in the pathogenesis of optineurin-associated amyotrophic lateral sclerosis [LiteratureReference:9828917] Cellular mechanisms controlling caspase activation and function |
| modified | [InstanceEdit:2566510] Orlic-Milacic, M, 2012-11-09 [InstanceEdit:9828914] Shamovsky, Veronica, 2023-02-20 |
| text | Tumor necrosis factor α (TNF-α)-induced apoptosis is regulated by the activity of caspase-8 (CASP8) (Micheau O and Tschopp J 2003; Justus SJ and Ting AT 2015). CASP8 is synthesized as an inactive precursor, pro-caspase-8, which is recruited to the cytosolic TRADD:TRAF2:RIPK1:FADD complex upon stimulation. Within this complex, multiple procaspase‑8 molecules interact via their tandem death‑effector domains (DED), thereby facilitating both proximity‑induced dimerization and proteolytic cleavage of procaspase‑8, which are required for initiation of apoptotic cell death (Keller N et al 2009; Oberst A et al. 2010). Activated CASP8 mediates cleavage and activation of effector caspases such as CASP3 to promote apoptosis, while cleavage of RIPK1, RIPK3 by CASP8 prevents RIPK1:RIPK3-dependent necroptosis (Parrish AB et al. 2013; Hopkins-Donaldson S et al. 2000; Newton K et al. 2019; Lalaoui N et al. 2020). When apoptosis is blocked, which occurs naturally in some cells or under certain pathophysiological conditions (e.g., expression of CASP8 inhibitory proteins such as CrmA and vICA after infection with cowpox virus or CMV and/or protein synthesis blockade that prevents NF-kappa-B-mediated expression of FLICE-inhibitory protein (cellular FLIP, CFLAR), deubiquitinated RIPK1 interacts with RIPK3 and MLKL to trigger necroptosis (Ofengeim D et al. 2015; Yuan J et al. 2019). This Reactome event shows pro-CASP8 binding to the cytosolic TRADD:TRAF2:RIPK1:FADD complex. This binding event is negatively regulated by optineurin (OPTN) (Nakazawa S et al. 2016). |
| (summation) | [Reaction:75240] TRADD:TRAF2:RIP1:FADD binds pro-caspase 8 [Homo sapiens] |
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No pathways have been reviewed or authored by Tumor necrosis factor α (TNF-α)-induced apoptosis is regulat... (179240)
