KEGG   PATHWAY: pmrn04217
Entry
pmrn04217                   Pathway                                
Name
Necroptosis - Petromyzon marinus (sea lamprey)
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
pmrn04217  Necroptosis
pmrn04217

Organism
Petromyzon marinus (sea lamprey) [GN:pmrn]
Gene
116956947  uncharacterized protein LOC116956947 isoform X1 [KO:K03158]
116950897  tumor necrosis factor receptor superfamily member 6-like [KO:K03158]
116958297  tumor necrosis factor receptor superfamily member 1A-like isoform X1 [KO:K03158]
116954117  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein isoform X1 [KO:K03171]
116957399  TNF receptor-associated factor 2-like isoform X1 [KO:K03173] [EC:2.3.2.27]
116957458  TNF receptor-associated factor 2-like isoform X1 [KO:K03173] [EC:2.3.2.27]
116944216  RIPK1; receptor-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K02861] [EC:2.7.11.1]
116946028  baculoviral IAP repeat-containing protein 7-like isoform X1 [KO:K04725] [EC:2.3.2.27]
116954119  SHARPIN; sharpin isoform X1 [KO:K10630] [EC:2.3.2.31]
116944207  RBCK1; ranBP-type and C3HC4-type zinc finger-containing protein 1 isoform X1 [KO:K10630] [EC:2.3.2.31]
116944277  RNF31; E3 ubiquitin-protein ligase RNF31 isoform X1 [KO:K11974] [EC:2.3.2.31]
116952120  spermatogenesis-associated protein 2-like [KO:K17595]
116954192  CYLD; ubiquitin carboxyl-terminal hydrolase CYLD [KO:K08601] [EC:3.4.19.12]
116956943  FAS-associated death domain protein-like [KO:K02373]
116946240  caspase-8-like isoform X1 [KO:K04724]
116945942  receptor-interacting serine/threonine-protein kinase 3-like isoform X1 [KO:K08847] [EC:2.7.11.1]
116940339  calcium/calmodulin-dependent protein kinase type II delta chain isoform X1 [KO:K04515] [EC:2.7.11.17]
116951021  calcium/calmodulin-dependent protein kinase type II delta chain-like isoform X1 [KO:K04515] [EC:2.7.11.17]
116942887  ADP/ATP translocase 1 [KO:K05863]
116943656  ADP/ATP translocase 1-like [KO:K05863]
116939250  voltage-dependent anion-selective channel protein 2-like [KO:K15040]
116940199  voltage-dependent anion-selective channel protein 2 [KO:K15040]
116940172  glutamate dehydrogenase, mitochondrial [KO:K00261] [EC:1.4.1.3]
116951068  glutamate dehydrogenase, mitochondrial-like [KO:K00261] [EC:1.4.1.3]
116953240  GLUL; glutamine synthetase [KO:K01915] [EC:6.3.1.2]
116939620  glycogen phosphorylase, muscle form-like [KO:K00688] [EC:2.4.1.1]
116947734  glycogen phosphorylase, brain form-like [KO:K00688] [EC:2.4.1.1]
116948344  PYGL; glycogen phosphorylase, liver form [KO:K00688] [EC:2.4.1.1]
116940312  mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
116951012  mitogen-activated protein kinase 8-like isoform X1 [KO:K04440] [EC:2.7.11.24]
116954127  ferritin heavy chain B-like [KO:K00522] [EC:1.16.3.1]
116954128  ferritin heavy chain B-like [KO:K00522] [EC:1.16.3.1]
116954129  ferritin heavy chain B-like [KO:K00522] [EC:1.16.3.1]
116954130  ferritin heavy chain B-like [KO:K00522] [EC:1.16.3.1]
116954521  ferritin heavy chain B-like [KO:K00522] [EC:1.16.3.1]
116954522  ferritin heavy chain B-like isoform X1 [KO:K00522] [EC:1.16.3.1]
116944397  ferritin heavy chain B-like [KO:K00522] [EC:1.16.3.1]
116944399  ferritin heavy chain, oocyte isoform-like [KO:K00522] [EC:1.16.3.1]
103091797  FTH1; ferritin heavy chain [KO:K00522] [EC:1.16.3.1]
116941294  PLA2G4F; cytosolic phospholipase A2 zeta [KO:K16342] [EC:3.1.1.4]
116944815  PLA2G4A; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
116939633  calpain-1 catalytic subunit-like [KO:K01367] [EC:3.4.22.52]
116939783  calpain-1 catalytic subunit-like [KO:K01367] [EC:3.4.22.52]
116947819  calpain-1 catalytic subunit-like [KO:K01367] [EC:3.4.22.52]
116943157  calpain-1 catalytic subunit-like [KO:K03853] [EC:3.4.22.53]
116943493  SMPD1; LOW QUALITY PROTEIN: sphingomyelin phosphodiesterase [KO:K12350] [EC:3.1.4.12]
116945914  MLKL; mixed lineage kinase domain-like protein [KO:K08849] [EC:2.7.11.1]
116939233  PGAM5; serine/threonine-protein phosphatase PGAM5, mitochondrial [KO:K15637] [EC:3.1.3.16]
116947541  DNM1L; dynamin-1-like protein isoform X1 [KO:K17065] [EC:3.6.5.5]
116952229  dynamin-1-like protein isoform X1 [KO:K17065] [EC:3.6.5.5]
116944762  caspase-1-A-like isoform X1 [KO:K01370] [EC:3.4.22.36]
116944392  CHMP2A; charged multivesicular body protein 2a [KO:K12191]
116938436  CHMP2B; charged multivesicular body protein 2b [KO:K12192]
116954247  charged multivesicular body protein 4c-like isoform X1 [KO:K12194]
116952193  charged multivesicular body protein 4b-like isoform X1 [KO:K12194]
116949551  CHMP6; charged multivesicular body protein 6 [KO:K12195]
116945999  vacuolar protein sorting-associated protein 4A isoform X1 [KO:K12196]
116954106  suppressor protein of bem1/bed5 double mutants-like isoform X1 [KO:K12196]
116954256  CHMP1A; charged multivesicular body protein 1a [KO:K12197]
116956657  CHMP1B; charged multivesicular body protein 1b [KO:K12197]
116940840  charged multivesicular body protein 5-like [KO:K12198]
116954740  CHMP5; charged multivesicular body protein 5 [KO:K12198]
116944702  CHMP7; charged multivesicular body protein 7 isoform X1 [KO:K15053]
116940949  transient receptor potential cation channel subfamily M member 7-like isoform X1 [KO:K04982] [EC:2.7.11.1]
116943614  high mobility group protein B1-like [KO:K10802]
116937479  tumor necrosis factor ligand superfamily member 10-like isoform X1 [KO:K04721]
116956968  uncharacterized protein LOC116956968 [KO:K04722]
116956896  tumor necrosis factor receptor superfamily member 6-like [KO:K04390]
116956897  tumor necrosis factor receptor superfamily member 6-like [KO:K04390]
116956951  tumor necrosis factor receptor superfamily member 23-like [KO:K04390]
116956967  tumor necrosis factor receptor superfamily member 6-like isoform X1 [KO:K04390]
116956969  tumor necrosis factor receptor superfamily member 6-like [KO:K04390]
116951928  tyrosine-protein kinase JAK2-like [KO:K04447] [EC:2.7.10.2]
116938726  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
116945023  signal transducer and activator of transcription 1-alpha/beta-like [KO:K04692]
116943942  signal transducer and activator of transcription 5B-like [KO:K11224]
116945041  signal transducer and activator of transcription 5A-like [KO:K11224]
116940177  toll-like receptor 3 isoform X1 [KO:K05401]
116955013  SQSTM1; sequestosome-1 [KO:K14381]
116939777  heat shock protein HSP 90-beta isoform X1 [KO:K04079]
116947664  heat shock protein HSP 90-alpha-like [KO:K04079]
116955620  TNFAIP3; tumor necrosis factor alpha-induced protein 3 isoform X1 [KO:K11859] [EC:3.4.19.12]
116947824  PARP1; poly [ADP-ribose] polymerase 1 [KO:K24070] [EC:2.4.2.30]
116958545  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
116944389  apoptosis regulator BAX-like [KO:K02159]
116943000  AIFM1; apoptosis-inducing factor 1, mitochondrial isoform X1 [KO:K04727] [EC:1.-.-.-]
116940298  core histone macro-H2A.1-like [KO:K11251]
116947679  histone H2A [KO:K11251]
116947680  histone H2A-like [KO:K11251]
116956901  histone H2A.V [KO:K11251]
116957093  histone H2AX [KO:K11251]
116950914  core histone macro-H2A.1 [KO:K11251]
116945029  peptidyl-prolyl cis-trans isomerase-like isoform X1 [KO:K03767] [EC:5.2.1.8]
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
pmrn00250  Alanine, aspartate and glutamate metabolism
pmrn04210  Apoptosis
KO pathway
ko04217   
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