KEGG   PATHWAY: brhi04217
Entry
brhi04217                   Pathway                                
Name
Necroptosis - Buceros rhinoceros silvestris (rhinoceros hornbill)
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 death
Pathway map
brhi04217  Necroptosis
brhi04217

Organism
Buceros rhinoceros silvestris (rhinoceros hornbill) [GN:brhi]
Gene
104489141  tumor necrosis factor receptor superfamily member 1A-like [KO:K03158]
104489993  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
104491295  TRAF5; TNF receptor-associated factor 5 [KO:K09849]
104492700  receptor-interacting serine/threonine-protein kinase 1-like [KO:K02861] [EC:2.7.11.1]
104498416  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
104488620  XIAP; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
104488693  BEAN1; protein BEAN1 [KO:K17595]
104492931  SPATA2; spermatogenesis-associated protein 2 [KO:K17595]
104499942  CYLD; ubiquitin carboxyl-terminal hydrolase CYLD [KO:K08601] [EC:3.4.19.12]
104489111  ubiquitin carboxyl-terminal hydrolase CYLD-like [KO:K08601] [EC:3.4.19.12]
104488312  FADD; FAS-associated death domain protein [KO:K02373]
104500748  caspase-8-like [KO:K04398] [EC:3.4.22.61]
104492696  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
104488191  CFLAR; CASP8 and FADD-like apoptosis regulator [KO:K04724]
104501226  calcium/calmodulin-dependent protein kinase type II subunit delta [KO:K04515] [EC:2.7.11.17]
104501493  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha [KO:K04515] [EC:2.7.11.17]
104489325  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta [KO:K04515] [EC:2.7.11.17]
104489904  ADP/ATP translocase 4-like [KO:K05863]
104494128  ADP/ATP translocase 3 [KO:K05863]
104500348  SLC25A4; ADP/ATP translocase 1 [KO:K05863]
104498324  SLC25A5; ADP/ATP translocase 2 [KO:K05863]
104491329  PPID; peptidyl-prolyl cis-trans isomerase D [KO:K05864] [EC:5.2.1.8]
104488324  VDAC1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
104493738  VDAC2; voltage-dependent anion-selective channel protein 2 isoform X1 [KO:K15040]
104488264  VDAC3; voltage-dependent anion-selective channel protein 3 [KO:K15041]
104492072  GLUD1; glutamate dehydrogenase 1, mitochondrial [KO:K00261] [EC:1.4.1.3]
104501345  glutamine synthetase [KO:K01915] [EC:6.3.1.2]
104499072  GLUL; glutamine synthetase [KO:K01915] [EC:6.3.1.2]
104492792  PYGB; glycogen phosphorylase, brain form [KO:K00688] [EC:2.4.1.1]
104494032  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
104490313  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
104495861  mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
104497186  FTH1; LOW QUALITY PROTEIN: ferritin heavy chain [KO:K00522] [EC:1.16.3.1]
104501843  PLA2G4A; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
104502198  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
104490921  PLA2G4B; cytosolic phospholipase A2 beta [KO:K16342] [EC:3.1.1.4]
104491246  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
104491247  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
104497939  PLA2G4F; cytosolic phospholipase A2 zeta [KO:K16342] [EC:3.1.1.4]
104493601  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
104493602  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
104498900  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
104494850  calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
104489251  CAPN2; calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
104497223  MLKL; mixed lineage kinase domain-like protein [KO:K08849] [EC:2.7.11.1]
104488309  PGAM5; serine/threonine-protein phosphatase PGAM5, mitochondrial [KO:K15637] [EC:3.1.3.16]
104492246  DNM1L; dynamin-1-like protein [KO:K17065] [EC:3.6.5.5]
104500195  IL1B; interleukin-1 beta [KO:K04519]
104497274  CHMP2B; charged multivesicular body protein 2b [KO:K12192]
104499883  CHMP3; charged multivesicular body protein 3 [KO:K12193]
104490580  CHMP4B; charged multivesicular body protein 4b [KO:K12194]
104493201  CHMP6; charged multivesicular body protein 6 [KO:K12195]
104498807  VPS4B; vacuolar protein sorting-associated protein 4B [KO:K12196]
104495227  CHMP1B; charged multivesicular body protein 1b [KO:K12197]
104488345  CHMP5; charged multivesicular body protein 5 [KO:K12198]
104489541  CHMP7; charged multivesicular body protein 7 [KO:K15053]
104501210  TRPM7; LOW QUALITY PROTEIN: transient receptor potential cation channel subfamily M member 7 [KO:K04982] [EC:2.7.11.1]
104498272  HMGB1; high mobility group protein B1 [KO:K10802]
104488403  TNFSF10; LOW QUALITY PROTEIN: tumor necrosis factor ligand superfamily member 10 [KO:K04721]
104497169  tumor necrosis factor receptor superfamily member 10B-like [KO:K04722]
104491291  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
104490889  tumor necrosis factor receptor superfamily member 6-like [KO:K04390]
104498037  interferon epsilon-like [KO:K05414]
104488934  interferon omega-1-like [KO:K05414]
104490459  IFNG; interferon gamma [KO:K04687]
104501093  IFNAR1; interferon alpha/beta receptor 1 [KO:K05130]
104495604  IFNAR2; interferon alpha/beta receptor 2 [KO:K05131]
104495059  IFNGR1; interferon gamma receptor 1 [KO:K05132]
104488528  IFNGR2; interferon gamma receptor 2 [KO:K05133]
104494851  JAK1; tyrosine-protein kinase JAK1 isoform X1 [KO:K11217] [EC:2.7.10.2]
104490703  JAK2; tyrosine-protein kinase JAK2 [KO:K04447] [EC:2.7.10.2]
104491544  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
104496281  STAT3; signal transducer and activator of transcription 3 [KO:K04692]
104500824  STAT4; signal transducer and activator of transcription 4 [KO:K11222]
104502187  EIF2AK2; interferon-induced, double-stranded RNA-activated protein kinase [KO:K16195] [EC:2.7.11.1]
104494590  TLR4; toll-like receptor 4 [KO:K10160]
104496118  TICAM1; TIR domain-containing adapter molecule 1 [KO:K05842]
104492452  TLR3; toll-like receptor 3 [KO:K05401]
104500790  SQSTM1; sequestosome-1 isoform X1 [KO:K14381]
104491958  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
104494708  TNFAIP3; tumor necrosis factor alpha-induced protein 3 [KO:K11859] [EC:3.4.19.12]
104493164  PARP1; poly [ADP-ribose] polymerase 1 [KO:K24070] [EC:2.4.2.30]
104491947  BID; BH3-interacting domain death agonist [KO:K04726]
104499410  apoptosis-inducing factor 1, mitochondrial-like [KO:K04727] [EC:1.-.-.-]
104500715  core histone macro-H2A.1 isoform X1 [KO:K11251]
104500260  core histone macro-H2A.2 isoform X1 [KO:K11251]
104491118  histone H2A isoform X1 [KO:K11251]
104488637  histone H2A.Z [KO:K11251]
104488691  histone H2A-beta, sperm-like [KO:K11251]
104488178  histone H2A-beta, sperm-like [KO:K11251]
104498762  peptidyl-prolyl cis-trans isomerase A [KO:K03767] [EC:5.2.1.8]
104493687  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
Compound
C00002  ATP
C00027  Hydrogen peroxide
C00076  Calcium cation
C00195  N-Acylsphingosine
C00219  Arachidonate
C00305  Magnesium cation
C00319  Sphingosine
C00550  Sphingomyelin
C14592  N-Methyl-N'-nitro-N-nitrosoguanidine
C16844  Hydroxyl radical
Reference
  Authors
Vandenabeele P, Galluzzi L, Vanden Berghe T, Kroemer G
  Title
Molecular mechanisms of necroptosis: an ordered cellular explosion.
  Journal
Nat Rev Mol Cell Biol 11:700-14 (2010)
DOI:10.1038/nrm2970
Reference
  Authors
Brenner D, Blaser H, Mak TW
  Title
Regulation of tumour necrosis factor signalling: live or let die.
  Journal
Nat Rev Immunol 15:362-74 (2015)
DOI:10.1038/nri3834
Reference
  Authors
Conrad M, Angeli JP, Vandenabeele P, Stockwell BR
  Title
Regulated necrosis: disease relevance and therapeutic opportunities.
  Journal
Nat Rev Drug Discov 15:348-66 (2016)
DOI:10.1038/nrd.2015.6
Reference
  Authors
Ofengeim D, Yuan J
  Title
Regulation of RIP1 kinase signalling at the crossroads of inflammation and cell death.
  Journal
Nat Rev Mol Cell Biol 14:727-36 (2013)
DOI:10.1038/nrm3683
Reference
  Authors
Murphy JM, Vince JE
  Title
Post-translational control of RIPK3 and MLKL mediated necroptotic cell death.
  Journal
F1000Res 4:F1000 Faculty Rev-1297 (2015)
DOI:10.12688/f1000research.7046.1
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
Nat Rev Mol Cell Biol 15:135-47 (2014)
DOI:10.1038/nrm3737
Reference
  Authors
Dondelinger Y, Hulpiau P, Saeys Y, Bertrand MJ, Vandenabeele P
  Title
An evolutionary perspective on the necroptotic pathway.
  Journal
Trends Cell Biol 26:721-32 (2016)
DOI:10.1016/j.tcb.2016.06.004
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
Cell Host Microbe 20:674-681 (2016)
DOI:10.1016/j.chom.2016.09.014
Reference
  Authors
Yuan J, Najafov A, Py BF
  Title
Roles of Caspases in Necrotic Cell Death.
  Journal
Cell 167:1693-1704 (2016)
DOI:10.1016/j.cell.2016.11.047
Reference
  Authors
Jorgensen I, Rayamajhi M, Miao EA
  Title
Programmed cell death as a defence against infection.
  Journal
Nat Rev Immunol 17:151-164 (2017)
DOI:10.1038/nri.2016.147
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
Sci Signal 3:re4 (2010)
DOI:10.1126/scisignal.3115re4
Reference
  Authors
Vanlangenakker N, Vanden Berghe T, Vandenabeele P
  Title
Many stimuli pull the necrotic trigger, an overview.
  Journal
Cell Death Differ 19:75-86 (2012)
DOI:10.1038/cdd.2011.164
Reference
  Authors
Moriwaki K, Chan FK
  Title
RIP3: a molecular switch for necrosis and inflammation.
  Journal
Genes Dev 27:1640-9 (2013)
DOI:10.1101/gad.223321.113
Reference
  Authors
Humphries F, Yang S, Wang B, Moynagh PN
  Title
RIP kinases: key decision makers in cell death and innate immunity.
  Journal
Cell Death Differ 22:225-36 (2015)
DOI:10.1038/cdd.2014.126
Reference
  Authors
Wegner KW, Saleh D, Degterev A
  Title
Complex Pathologic Roles of RIPK1 and RIPK3: Moving Beyond Necroptosis.
  Journal
Trends Pharmacol Sci 38:202-225 (2017)
DOI:10.1016/j.tips.2016.12.005
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
Cell Rep 16:2271-80 (2016)
DOI:10.1016/j.celrep.2016.07.086
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
Dev Cell 37:337-49 (2016)
DOI:10.1016/j.devcel.2016.04.018
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
J Biol Chem 285:969-78 (2010)
DOI:10.1074/jbc.M109.042689
Reference
  Authors
Jacobsen AV, Silke J
  Title
The importance of being chaperoned: HSP90 and necroptosis.
  Journal
Cell Chem Biol 23:205-7 (2016)
DOI:10.1016/j.chembiol.2016.02.003
Reference
  Authors
Gurung P, Man SM, Kanneganti TD
  Title
A20 is a regulator of necroptosis.
  Journal
Nat Immunol 16:596-7 (2015)
DOI:10.1038/ni.3174
Reference
  Authors
Feng N, Anderson ME
  Title
CaMKII is a nodal signal for multiple programmed cell death pathways in heart.
  Journal
J Mol Cell Cardiol 103:102-109 (2017)
DOI:10.1016/j.yjmcc.2016.12.007
Reference
  Authors
Zhivotovsky B, Galluzzi L, Kepp O, Kroemer G
  Title
Adenine nucleotide translocase: a component of the phylogenetically conserved cell death machinery.
  Journal
Cell Death Differ 16:1419-25 (2009)
DOI:10.1038/cdd.2009.118
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
Proc Natl Acad Sci U S A 110:E3109-18 (2013)
DOI:10.1073/pnas.1301218110
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
Mol Cell Biol 31:2934-46 (2011)
DOI:10.1128/MCB.05445-11
Reference
  Authors
Sridharan H, Upton JW
  Title
Programmed necrosis in microbial pathogenesis.
  Journal
Trends Microbiol 22:199-207 (2014)
DOI:10.1016/j.tim.2014.01.005
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
Cell Death Differ 19:245-56 (2012)
DOI:10.1038/cdd.2011.91
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
Cell Cycle 9:3166-73 (2010)
DOI:10.4161/cc.9.16.12887
Reference
  Authors
Upton JW, Kaiser WJ
  Title
DAI Another Way: Necroptotic Control of Viral Infection.
  Journal
Cell Host Microbe 21:290-293 (2017)
DOI:10.1016/j.chom.2017.01.016
Reference
  Authors
Silke J, Rickard JA, Gerlic M
  Title
The diverse role of RIP kinases in necroptosis and inflammation.
  Journal
Nat Immunol 16:689-97 (2015)
DOI:10.1038/ni.3206
Reference
  Authors
Guo H, Kaiser WJ
  Title
ESCRTing Necroptosis.
  Journal
Cell 169:186-187 (2017)
DOI:10.1016/j.cell.2017.03.030
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
Cell 169:286-300.e16 (2017)
DOI:10.1016/j.cell.2017.03.020
Reference
  Authors
Petrie EJ, Hildebrand JM, Murphy JM
  Title
Insane in the membrane: a structural perspective of MLKL function in necroptosis.
  Journal
Immunol Cell Biol 95:152-159 (2017)
DOI:10.1038/icb.2016.125
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
Nat Cell Biol 16:55-65 (2014)
DOI:10.1038/ncb2883
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
Nat Commun 6:6282 (2015)
DOI:10.1038/ncomms7282
Reference
  Authors
Shlomovitz I, Zargrian S, Gerlic M
  Title
Mechanisms of RIPK3-induced inflammation.
  Journal
Immunol Cell Biol 95:166-172 (2017)
DOI:10.1038/icb.2016.124
Related
pathway
brhi00250  Alanine, aspartate and glutamate metabolism
brhi04210  Apoptosis
KO pathway
ko04217   
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