Entry Name Necroptosis
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 Orthology K00261 GLUD1_2, gdhA; glutamate dehydrogenase (NAD(P)+) [EC:1.4.1.3 ]
K02159 BAX; apoptosis regulator BAX
K02161 BCL2; apoptosis regulator Bcl-2
K02373 FADD; FAS-associated death domain protein
K02861 RIPK1, RIP1; receptor-interacting serine/threonine-protein kinase 1 [EC:2.7.11.1 ]
K03156 TNF, TNFA; tumor necrosis factor superfamily, member 2
K03158 TNFRSF1A, TNFR1, CD120a; tumor necrosis factor receptor superfamily member 1A
K03171 TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein
K03767 PPIA; peptidyl-prolyl cis-trans isomerase A (cyclophilin A) [EC:5.2.1.8 ]
K04079 HSP90A, htpG; molecular chaperone HtpG
K04383 IL1A; interleukin 1 alpha
K04389 TNFSF6, FASL, CD178; tumor necrosis factor ligand superfamily member 6
K04390 TNFRSF6, FAS, CD95; tumor necrosis factor receptor superfamily member 6
K04440 JNK; mitogen-activated protein kinase 8/9/10 (c-Jun N-terminal kinase) [EC:2.7.11.24 ]
K04515 CAMK2; calcium/calmodulin-dependent protein kinase (CaM kinase) II [EC:2.7.11.17 ]
K04519 IL1B; interleukin 1 beta
K04692 STAT3; signal transducer and activator of transcription 3
K04693 IRF9, ISGF3G, P48; interferon regulatory factor 9
K04721 TNFSF10, TRAIL, CD253; tumor necrosis factor ligand superfamily member 10
K04722 TNFRSF10A_B, TRAILR1_2, DR4_5, CD261_2; tumor necrosis factor receptor superfamily member 10A/B
K04724 CFLAR, FLIP; CASP8 and FADD-like apoptosis regulator
K04726 BID; BH3 interacting domain death agonist
K04727 AIFM1, PDCD8; apoptosis-inducing factor 1 [EC:1.-.-.-]
K04982 TRPM7, CHAK1; transient receptor potential cation channel subfamily M member 7 [EC:2.7.11.1 ]
K05130 IFNAR1; interferon receptor 1
K05131 IFNAR2; interferon receptor 2
K05132 IFNGR1, CD119; interferon gamma receptor 1
K05133 IFNGR2; interferon gamma receptor 2
K05401 TLR3, CD283; toll-like receptor 3
K05409 TIRP, TRAM; TRIF-related adaptor molecule
K05842 TRIF; toll-like receptor adapter molecule 1
K05862 VDAC1; voltage-dependent anion channel protein 1
K05863 SLC25A4S, ANT; solute carrier family 25 (mitochondrial adenine nucleotide translocator), member 4/5/6/31
K08601 CYLD, USLP2; ubiquitin carboxyl-terminal hydrolase CYLD [EC:3.4.19.12 ]
K08847 RIPK3; receptor-interacting serine/threonine-protein kinase 3 [EC:2.7.11.1 ]
K09849 TRAF5; TNF receptor-associated factor 5
K10160 TLR4, CD284; toll-like receptor 4
K10630 RBCK1, HOIL1; RanBP-type and C3HC4-type zinc finger-containing protein 1 [EC:2.3.2.31 ]
K10802 HMGB1; high mobility group protein B1
K11220 STAT1; signal transducer and activator of transcription 1
K11221 STAT2; signal transducer and activator of transcription 2
K11222 STAT4; signal transducer and activator of transcription 4
K11223 STAT5A; signal transducer and activator of transcription 5A
K11224 STAT5B; signal transducer and activator of transcription 5B
K11225 STAT6; signal transducer and activator of transcription 6
K11859 TNFAIP3, A20, OTUD7C; tumor necrosis factor, alpha-induced protein 3 [EC:3.4.19.12 ]
K12191 CHMP2A; charged multivesicular body protein 2A
K12192 CHMP2B; charged multivesicular body protein 2B
K12193 VPS24, CHMP3; charged multivesicular body protein 3
K12194 CHMP4A_B, SNF7, VPS32A_B; charged multivesicular body protein 4A/B
K12195 CHMP6, VPS20; charged multivesicular body protein 6
K12196 VPS4; vacuolar protein-sorting-associated protein 4
K12197 CHMP1, VPS46, DID2; charged multivesicular body protein 1
K12198 CHMP5, VPS60; charged multivesicular body protein 5
K12799 PYCARD, ASC; apoptosis-associated speck-like protein containing a CARD
K12800 NLRP3, PYPAF1; NACHT, LRR and PYD domains-containing protein 3
K12965 ZBP1, DAI; Z-DNA binding protein 1
K13625 FTL; ferritin light chain
K15040 VDAC2; voltage-dependent anion channel protein 2
K15041 VDAC3; voltage-dependent anion channel protein 3
K15053 CHMP7; charged multivesicular body protein 7
K15637 PGAM5; serine/threonine-protein phosphatase PGAM5 [EC:3.1.3.16 ]
K16060 BIRC2_3; baculoviral IAP repeat-containing protein 2/3
K16195 EIF2AK2; eukaryotic translation initiation factor 2-alpha kinase 2 [EC:2.7.11.1 ]
K17595 SPATA2; spermatogenesis-associated protein 2
K20894 SHARPIN; shank-associated RH domain-interacting protein
K21421 NOX2, GP91, CYBB; NADPH oxidase 2 [EC:1.-.-.-]
K24070 PARP1; poly [ADP-ribose] polymerase 1
K24782 CHMP4C, SNF7, VPS32C; charged multivesicular body protein 4C
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 ko00250 Alanine, aspartate and glutamate metabolism
