Entry Name Necroptosis - Ailuropoda melanoleuca (giant panda)
Description Necroptosis is a programmed form of necrosis. It can be initiated by different stimuli, such as tumor necrosis factor (TNF), TNF-related apoptosis-inducing ligand (TRAIL), Fas ligand (FasL), interferon (IFN), LPS, viral DNA or RNA, DNA-damage agent and requires the kinase activity of receptor-interacting protein 1 (RIPK1) and RIPK3. Its execution involves ROS generation, calcium overload, the opening of the mitochondrial permeability transition pore, mitochondrial fission, inflammatory response and chromatinolysis. Necroptosis participates in many pathogenesis of diseases, including neurological diseases, retinal disorders, acute kidney injury, inflammatory diseases and microbial infections.
Class Cellular Processes; Cell growth and deathBRITE hierarchy
Pathway map Ortholog table Organism Ailuropoda melanoleuca (giant panda) [GN:
aml ]
Gene 100479926 TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158 ]
100483589 TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein isoform X1 [KO:K03171 ]
100477152 baculoviral IAP repeat-containing protein 3 isoform X1 [KO:K16060 ]
100465864 SPATA2L; spermatogenesis-associated protein 2-like protein isoform X1 [KO:K17595 ]
100474872 CFLAR; CASP8 and FADD-like apoptosis regulator isoform X4 [KO:K04724 ]
100475467 CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X2 [KO:K04515 ] [EC:2.7.11.17 ]
100466256 CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X5 [KO:K04515 ] [EC:2.7.11.17 ]
100474459 CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X3 [KO:K04515 ] [EC:2.7.11.17 ]
100463625 VDAC1; voltage-dependent anion-selective channel protein 1 [KO:K05862 ]
100465507 VDAC2; voltage-dependent anion-selective channel protein 2 [KO:K15040 ]
100470763 VDAC3; voltage-dependent anion-selective channel protein 3 isoform X1 [KO:K15041 ]
100468792 NLRP3; NACHT, LRR and PYD domains-containing protein 3 isoform X1 [KO:K12800 ]
100475582 apoptosis-associated speck-like protein containing a CARD isoform X1 [KO:K12799 ]
100482517 RNF103; E3 ubiquitin-protein ligase RNF103 isoform X3 [KO:K12193 ]
100478745 VPS4A; vacuolar protein sorting-associated protein 4A isoform X1 [KO:K12196 ]
100484849 VPS4B; vacuolar protein sorting-associated protein 4B [KO:K12196 ]
100465356 CHMP1A; charged multivesicular body protein 1a isoform X2 [KO:K12197 ]
100482433 TRPM7; transient receptor potential cation channel subfamily M member 7 isoform X1 [KO:K04982 ] [EC:2.7.11.1 ]
100463573 TNFSF10; tumor necrosis factor ligand superfamily member 10 [KO:K04721 ]
105235183 tumor necrosis factor receptor superfamily member 10A-like [KO:K04722 ]
100468235 FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389 ]
100473767 FAS; tumor necrosis factor receptor superfamily member 6 [KO:K04390 ]
100474026 STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220 ]
100472167 STAT2; signal transducer and activator of transcription 2 isoform X1 [KO:K11221 ]
100469938 STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692 ]
100471596 STAT4; signal transducer and activator of transcription 4 isoform X3 [KO:K11222 ]
100476198 STAT6; signal transducer and activator of transcription 6 isoform X1 [KO:K11225 ]
100469151 EIF2AK2; interferon-induced, double-stranded RNA-activated protein kinase isoform X1 [KO:K16195 ] [EC:2.7.11.1 ]
100471414 HSP90AB1; LOW QUALITY PROTEIN: heat shock protein HSP 90-beta [KO:K04079 ]
100467363 HSP90AA1; LOW QUALITY PROTEIN: heat shock protein HSP 90-alpha [KO:K04079 ]
117803466 LOW QUALITY PROTEIN: heat shock protein HSP 90-beta-like [KO:K04079 ]
100471854 AIFM1; apoptosis-inducing factor 1, mitochondrial isoform X1 [KO:K04727 ] [EC:1.-.-.-]
Compound C14592 N-Methyl-N'-nitro-N-nitrosoguanidine
Reference Authors Vandenabeele P, Galluzzi L, Vanden Berghe T, Kroemer G
Title Molecular mechanisms of necroptosis: an ordered cellular explosion.
Journal Reference Authors Brenner D, Blaser H, Mak TW
Title Regulation of tumour necrosis factor signalling: live or let die.
Journal Reference Authors Conrad M, Angeli JP, Vandenabeele P, Stockwell BR
Title Regulated necrosis: disease relevance and therapeutic opportunities.
Journal Reference Authors Ofengeim D, Yuan J
Title Regulation of RIP1 kinase signalling at the crossroads of inflammation and cell death.
Journal Reference Authors Murphy JM, Vince JE
Title Post-translational control of RIPK3 and MLKL mediated necroptotic cell death.
Journal Reference Authors Vanden Berghe T, Linkermann A, Jouan-Lanhouet S, Walczak H, Vandenabeele P
Title Regulated necrosis: the expanding network of non-apoptotic cell death pathways.
Journal Reference Authors Dondelinger Y, Hulpiau P, Saeys Y, Bertrand MJ, Vandenabeele P
Title An evolutionary perspective on the necroptotic pathway.
Journal Reference Authors Thapa RJ, Ingram JP, Ragan KB, Nogusa S, Boyd DF, Benitez AA, Sridharan H, Kosoff R, Shubina M, Landsteiner VJ, Andrake M, Vogel P, Sigal LJ, tenOever BR, Thomas PG, Upton JW, Balachandran S
Title DAI Senses Influenza A Virus Genomic RNA and Activates RIPK3-Dependent Cell Death.
Journal Reference Authors Yuan J, Najafov A, Py BF
Title Roles of Caspases in Necrotic Cell Death.
Journal Reference Authors Jorgensen I, Rayamajhi M, Miao EA
Title Programmed cell death as a defence against infection.
Journal Reference Authors Vandenabeele P, Declercq W, Van Herreweghe F, Vanden Berghe T
Title The role of the kinases RIP1 and RIP3 in TNF-induced necrosis.
Journal Reference Authors Vanlangenakker N, Vanden Berghe T, Vandenabeele P
Title Many stimuli pull the necrotic trigger, an overview.
Journal Reference Authors Moriwaki K, Chan FK
Title RIP3: a molecular switch for necrosis and inflammation.
Journal Reference Authors Humphries F, Yang S, Wang B, Moynagh PN
Title RIP kinases: key decision makers in cell death and innate immunity.
Journal Reference Authors Wegner KW, Saleh D, Degterev A
Title Complex Pathologic Roles of RIPK1 and RIPK3: Moving Beyond Necroptosis.
Journal Reference Authors Kupka S, De Miguel D, Draber P, Martino L, Surinova S, Rittinger K, Walczak H
Title SPATA2-Mediated Binding of CYLD to HOIP Enables CYLD Recruitment to Signaling Complexes.
Journal Reference Authors Goodall ML, Fitzwalter BE, Zahedi S, Wu M, Rodriguez D, Mulcahy-Levy JM, Green DR, Morgan M, Cramer SD, Thorburn A
Title The Autophagy Machinery Controls Cell Death Switching between Apoptosis and Necroptosis.
Journal Reference Authors Xu G, Tan X, Wang H, Sun W, Shi Y, Burlingame S, Gu X, Cao G, Zhang T, Qin J, Yang J
Title Ubiquitin-specific peptidase 21 inhibits tumor necrosis factor alpha-induced nuclear factor kappaB activation via binding to and deubiquitinating receptor-interacting protein 1.
Journal Reference Authors Jacobsen AV, Silke J
Title The importance of being chaperoned: HSP90 and necroptosis.
Journal Reference Authors Gurung P, Man SM, Kanneganti TD
Title A20 is a regulator of necroptosis.
Journal Reference Authors Feng N, Anderson ME
Title CaMKII is a nodal signal for multiple programmed cell death pathways in heart.
Journal Reference Authors Zhivotovsky B, Galluzzi L, Kepp O, Kroemer G
Title Adenine nucleotide translocase: a component of the phylogenetically conserved cell death machinery.
Journal Reference Authors Thapa RJ, Nogusa S, Chen P, Maki JL, Lerro A, Andrake M, Rall GF, Degterev A, Balachandran S
Title Interferon-induced RIP1/RIP3-mediated necrosis requires PKR and is licensed by FADD and caspases.
Journal Reference Authors Thapa RJ, Basagoudanavar SH, Nogusa S, Irrinki K, Mallilankaraman K, Slifker MJ, Beg AA, Madesh M, Balachandran S
Title NF-kappaB protects cells from gamma interferon-induced RIP1-dependent necroptosis.
Journal Reference Authors Sridharan H, Upton JW
Title Programmed necrosis in microbial pathogenesis.
Journal Reference Authors Cabon L, Galan-Malo P, Bouharrour A, Delavallee L, Brunelle-Navas MN, Lorenzo HK, Gross A, Susin SA
Title BID regulates AIF-mediated caspase-independent necroptosis by promoting BAX activation.
Journal Reference Authors Baritaud M, Boujrad H, Lorenzo HK, Krantic S, Susin SA
Title Histone H2AX: The missing link in AIF-mediated caspase-independent programmed necrosis.
Journal Reference Authors Upton JW, Kaiser WJ
Title DAI Another Way: Necroptotic Control of Viral Infection.
Journal Reference Authors Silke J, Rickard JA, Gerlic M
Title The diverse role of RIP kinases in necroptosis and inflammation.
Journal Reference Authors Guo H, Kaiser WJ
Title ESCRTing Necroptosis.
Journal Reference Authors Gong YN, Guy C, Olauson H, Becker JU, Yang M, Fitzgerald P, Linkermann A, Green DR
Title ESCRT-III Acts Downstream of MLKL to Regulate Necroptotic Cell Death and Its Consequences.
Journal Reference Authors Petrie EJ, Hildebrand JM, Murphy JM
Title Insane in the membrane: a structural perspective of MLKL function in necroptosis.
Journal Reference Authors Cai Z, Jitkaew S, Zhao J, Chiang HC, Choksi S, Liu J, Ward Y, Wu LG, Liu ZG
Title Plasma membrane translocation of trimerized MLKL protein is required for TNF-induced necroptosis.
Journal Reference Authors Lawlor KE, Khan N, Mildenhall A, Gerlic M, Croker BA, D'Cruz AA, Hall C, Kaur Spall S, Anderton H, Masters SL, Rashidi M, Wicks IP, Alexander WS, Mitsuuchi Y, Benetatos CA, Condon SM, Wong WW, Silke J, Vaux DL, Vince JE
Title RIPK3 promotes cell death and NLRP3 inflammasome activation in the absence of MLKL.
Journal Reference Authors Shlomovitz I, Zargrian S, Gerlic M
Title Mechanisms of RIPK3-induced inflammation.
Journal Related aml00250 Alanine, aspartate and glutamate metabolism
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