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necroptotic signaling pathway

Term Information

Accession
GO:0097527
Name
necroptotic signaling pathway
Ontology
biological_process
Synonyms
necroptosis signaling pathway, necroptotic signal transduction, necroptosis signaling, necroptotic signalling pathway
Alternate IDs
None
Definition
The 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. Source: PMID:20823910, GOC:mtg_apoptosis
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.
History
See term history for GO:0097527 at QuickGO
Subset
None
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Parents of necroptotic signaling pathway (GO:0097527)
subject[Reorder by subject] relation[Reorder by relation] object[Reorder by object]
necroptotic signaling pathway [is_a relation] is_a  signal transduction (GO:0007165)
necroptotic signaling pathway [BFO:0000050 relation] BFO:0000050  necroptotic process (GO:0070266)

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None.