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Term:necroptotic signaling pathway
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Accession:GO:0097527 term browser browse the term
Definition:A series of molecular signals which triggers the necroptotic death of a cell. The pathway starts with reception of a signal, is characterized by activation of receptor-interacting serine/threonine-protein kinase 1 and/or 3 (RIPK1/3, also called RIP1/3), and ends when the execution phase of necroptosis is triggered.
Comment:Gene products that may be annotated to this term include: 1) ligands such as TNF-alpha; 2) receptors such as TNFR (though care should be taken because TNF-alpha and TNFR may also be involved in non-necroptotic processes); 3) signaling molecules such as TNFR-associated death domain (TRADD), receptor-interacting protein kinase 1 (RIP1), cellular inhibitor of apoptosis 1 (cIAP1), cIAP2, TNFR-associated factor 2 (TRAF2) and TRAF5. Within the so-called complex I, RIP1 is polyubiquitinated by cIAPs, thereby providing a docking site for the recruitment of transforming growth factor beta (TGFbeta)-activated kinase 1 (TAK1), TAK1-binding protein 2 (TAB2) and TAB3 (which together deliver a pro-survival signal by activating the transcription factor NF-kB). In some pathophysiological and experimental settings, and in particular when caspase-8 is absent or when caspases are inhibited by pharmacological agents, cylindromatosis (CYLD)-deubiquitinated RIP1 engage in physical and functional interactions with its homolog RIP3, ultimately activating the execution of necrotic cell death. (The pathway downstream of RIPK3 remains largely unknown, although ROS generation, calcium overload, and the opening of the mitochondrial permeability transition pore have been implicated (PMID:22265414)). A necroptotic signaling pathway may also be induced by alkylating DNA damage (possibly by the overactivation of poly(ADP-ribose) polymerase 1, PARP1). This is sometimes referred to as PARP-dependent cell death or parthanatos; it is still being debated if it constitutes an independent cell death modality.
Synonyms:exact_synonym: necroptosis signaling pathway;   necroptotic signal transduction
 related_synonym: necroptosis signaling;   necroptotic signalling pathway

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necroptotic signaling pathway term browser
Symbol Object Name JBrowse Chr Start Stop Reference
G Fadd Fas associated via death domain JBrowse link 1 217,746,176 217,748,581 RGD:1624291
G Fas Fas cell surface death receptor JBrowse link 1 252,589,785 252,624,790 RGD:1624291
G Faslg Fas ligand JBrowse link 13 79,696,811 79,717,581 RGD:1624291
G LOC103694380 tumor necrosis factor-like JBrowse link 20 4,855,792 4,858,447 RGD:1600115
G Mlkl mixed lineage kinase domain like pseudokinase JBrowse link 19 43,508,416 43,535,050 RGD:1624291
G Ripk1 receptor interacting serine/threonine kinase 1 JBrowse link 17 31,537,580 31,569,904 RGD:1600115
G Ripk3 receptor-interacting serine-threonine kinase 3 JBrowse link 15 34,470,796 34,479,741 RGD:1624291
G Tlr3 toll-like receptor 3 JBrowse link 16 50,016,466 50,031,011 RGD:1624291
G Tnf tumor necrosis factor JBrowse link 20 5,189,382 5,192,000 RGD:1600115

Term paths to the root
Path 1
Term Annotations click to browse term
  biological_process 19858
    cellular process 18618
      signal transduction 6968
        necroptotic signaling pathway 9
Path 2
Term Annotations click to browse term
  biological_process 19858
    cellular process 18618
      cell death 2138
        necrotic cell death 62
          programmed necrotic cell death 45
            necroptotic process 35
              necroptotic signaling pathway 9
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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.