KEGG   PATHWAY: leri04217
Entry
leri04217                   Pathway                                
Name
Necroptosis - Leucoraja erinacea (little skate)
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
leri04217  Necroptosis
leri04217

Organism
Leucoraja erinacea (little skate) [GN:leri]
Gene
129694589  tumor necrosis factor-like [KO:K03156]
129694591  lymphotoxin-alpha-like [KO:K03156]
129715888  tumor necrosis factor-like [KO:K03156]
129713374  uncharacterized protein LOC129713374 isoform X1 [KO:K03158]
129705160  tradd; LOW QUALITY PROTEIN: tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
129711946  TNF receptor-associated factor 2-like isoform X1 [KO:K03173] [EC:2.3.2.27]
129693903  TNF receptor-associated factor 2-like [KO:K03173] [EC:2.3.2.27]
129694202  TNF receptor-associated factor 2-like [KO:K03173] [EC:2.3.2.27]
129699700  TNF receptor-associated factor 5-like isoform X1 [KO:K09849]
129708079  ripk1l; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
129698291  birc2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
129702043  E3 ubiquitin-protein ligase XIAP-like isoform X1 [KO:K04725] [EC:2.3.2.27]
129707313  rbck1; ranBP-type and C3HC4-type zinc finger-containing protein 1 isoform X1 [KO:K10630] [EC:2.3.2.31]
129715055  shrprbck1r; ranBP-type and C3HC4-type zinc finger-containing protein 1 [KO:K10630] [EC:2.3.2.31]
129705309  si:ch211-189a15.5; uncharacterized protein si:ch211-189a15.5 [KO:K17595]
129705397  spata2l; spermatogenesis associated 2-like [KO:K17595]
129707452  spata2; spermatogenesis-associated protein 2 [KO:K17595]
129705036  cylda; ubiquitin carboxyl-terminal hydrolase CYLD [KO:K08601] [EC:3.4.19.12]
129706124  LOW QUALITY PROTEIN: ubiquitin carboxyl-terminal hydrolase CYLD-like [KO:K08601] [EC:3.4.19.12]
129698865  caspase-8-like isoform X1 [KO:K04398] [EC:3.4.22.61]
129698952  CASP8 and FADD-like apoptosis regulator [KO:K04724]
129702683  cytochrome b-245 heavy chain [KO:K21421] [EC:1.-.-.-]
129701572  calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
129713199  calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
129700367  calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
129712893  camk2g2; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
129695241  slc25a4; ADP/ATP translocase 1 [KO:K05863]
129702317  slc25a5; ADP/ATP translocase 2 [KO:K05863]
129704457  ADP/ATP translocase 4-like [KO:K05863]
129703439  ppid; peptidyl-prolyl cis-trans isomerase D [KO:K05864] [EC:5.2.1.8]
129701805  voltage-dependent anion-selective channel protein 1-like [KO:K05862]
129712859  voltage-dependent anion-selective channel protein 2 [KO:K15040]
129713388  vdac3; voltage-dependent anion-selective channel protein 3 [KO:K15041]
129713036  glutamate dehydrogenase, mitochondrial [KO:K00261] [EC:1.4.1.3]
129711923  glutamine synthetase-like [KO:K01915] [EC:6.3.1.2]
129701080  glutamine synthetase, mitochondrial isoform X1 [KO:K01915] [EC:6.3.1.2]
129699492  glycogen phosphorylase, brain form [KO:K00688] [EC:2.4.1.1]
129700153  glycogen phosphorylase, brain form-like isoform X1 [KO:K00688] [EC:2.4.1.1]
129715398  glycogen phosphorylase, muscle form-like [KO:K00688] [EC:2.4.1.1]
129712993  mapk8b; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
129701740  mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
129699899  mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
129695501  ferritin heavy chain-like [KO:K00522] [EC:1.16.3.1]
129713711  ferritin, heavy subunit-like [KO:K00522] [EC:1.16.3.1]
129713912  ferritin heavy chain-like [KO:K00522] [EC:1.16.3.1]
129713913  ferritin, lower subunit-like [KO:K00522] [EC:1.16.3.1]
129713914  ferritin heavy chain-like [KO:K00522] [EC:1.16.3.1]
129705780  fth1a; ferritin, heavy polypeptide 1a [KO:K00522] [EC:1.16.3.1]
129699985  ferritin heavy chain, oocyte isoform-like [KO:K00522] [EC:1.16.3.1]
129700513  cytosolic phospholipase A2 zeta-like [KO:K16342] [EC:3.1.1.4]
129701123  cytosolic phospholipase A2-like isoform X1 [KO:K16342] [EC:3.1.1.4]
129697548  LOW QUALITY PROTEIN: calpain-1 catalytic subunit-like [KO:K01367] [EC:3.4.22.52]
129699624  calpain-2 catalytic subunit-like [KO:K03853] [EC:3.4.22.53]
129698345  smpd1; LOW QUALITY PROTEIN: sphingomyelin phosphodiesterase [KO:K12350] [EC:3.1.4.12]
129705176  mixed lineage kinase domain-like protein [KO:K08849] [EC:2.7.11.1]
129709268  pgam5; serine/threonine-protein phosphatase PGAM5, mitochondrial isoform X1 [KO:K15637] [EC:3.1.3.16]
129706151  dnm1l; dynamin-1-like protein isoform X1 [KO:K17065] [EC:3.6.5.5]
129695177  uncharacterized protein LOC129695177 isoform X1 [KO:K12799]
129710763  caspase-1-A-like [KO:K01370] [EC:3.4.22.36]
129713422  interleukin-1 beta-like [KO:K04519]
129714010  chmp2a; charged multivesicular body protein 2a [KO:K12191]
129702931  charged multivesicular body protein 2b-like [KO:K12192]
129705418  charged multivesicular body protein 3-like isoform X1 [KO:K12193]
129707333  chmp4ba; charged multivesicular body protein 4b isoform X1 [KO:K12194]
129696376  charged multivesicular body protein 4b-like isoform X1 [KO:K24782]
129708214  chmp6b; charged multivesicular body protein 6 [KO:K12195]
129711555  vacuolar protein sorting-associated protein 4B-like [KO:K12196]
129715074  vacuolar protein sorting-associated protein 4A [KO:K12196]
129705395  chmp1a; charged multivesicular body protein 1a [KO:K12197]
129702383  chmp1b; charged multivesicular body protein 1b [KO:K12197]
129713679  charged multivesicular body protein 5 [KO:K12198]
129713685  charged multivesicular body protein 5 [KO:K12198]
129713147  chmp7; LOW QUALITY PROTEIN: charged multivesicular body protein 7 [KO:K15053]
129712684  trpm7; transient receptor potential cation channel subfamily M member 7 [KO:K04982] [EC:2.7.11.1]
129703412  tnfsf10; tumor necrosis factor ligand superfamily member 10 [KO:K04721]
129701294  LOW QUALITY PROTEIN: tumor necrosis factor ligand superfamily member 6-like [KO:K04389]
129701295  tumor necrosis factor ligand superfamily member 6-like [KO:K04389]
129715694  tumor necrosis factor ligand superfamily member 6-like [KO:K04389]
129704265  tumor necrosis factor receptor superfamily member 6-like [KO:K04390]
129710038  interferon alpha-10-like [KO:K05414]
129710039  interferon alpha-2-like [KO:K05414]
129710040  interferon alpha-F-like [KO:K05414]
129710041  interferon alpha-2-like [KO:K05414]
129710045  interferon alpha-B-like isoform X1 [KO:K05414]
129710046  interferon alpha-21-like [KO:K05414]
129710396  interferon alpha-1/13-like [KO:K05414]
129710398  interferon tau-3-like [KO:K05414]
129710399  interferon alpha-1-like isoform X1 [KO:K05414]
129710400  interferon tau-3-like [KO:K05414]
129710401  interferon tau-3-like [KO:K05414]
129701095  jak1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
129695436  tyrosine-protein kinase JAK2-like isoform X1 [KO:K04447] [EC:2.7.10.2]
129711208  tyrosine-protein kinase JAK2-like [KO:K04447] [EC:2.7.10.2]
129714534  tyk2; non-receptor tyrosine-protein kinase TYK2 [KO:K11219] [EC:2.7.10.2]
129698644  signal transducer and activator of transcription 1-alpha/beta-like isoform X1 [KO:K11220]
129714674  signal transducer and activator of transcription 1-like isoform X1 [KO:K11220]
129710261  stat3; signal transducer and activator of transcription 3 [KO:K04692]
129698548  signal transducer and activator of transcription 4-like [KO:K11222]
129710260  stat5a; signal transducer and activator of transcription 5A isoform X1 [KO:K11224]
129714703  signal transducer and activator of transcription 5B-like isoform X1 [KO:K11224]
129696980  eif2ak2; interferon-induced, double-stranded RNA-activated protein kinase [KO:K16195] [EC:2.7.11.1]
129695209  tlr3; toll-like receptor 3 [KO:K05401]
129708715  ubiquitin carboxyl-terminal hydrolase 2-like [KO:K21634] [EC:3.4.19.12]
129701581  sqstm1; sequestosome-1 isoform X1 [KO:K14381]
129697595  hsp90ab1; heat shock protein HSP 90-beta [KO:K04079]
129700542  heat shock protein HSP 90-alpha [KO:K04079]
129697404  tnfaip3; tumor necrosis factor alpha-induced protein 3 isoform X1 [KO:K11859] [EC:3.4.19.12]
129697683  parp1; poly [ADP-ribose] polymerase 1 [KO:K24070] [EC:2.4.2.30]
129706074  BH3-interacting domain death agonist-like isoform X1 [KO:K04726]
129705596  zgc:153993; apoptosis regulator BAX [KO:K02159]
129713845  apoptosis regulator BAX-like isoform X1 [KO:K02159]
129702246  aifm1; apoptosis-inducing factor 1, mitochondrial isoform X1 [KO:K04727] [EC:1.-.-.-]
129695172  histone H2AX-like [KO:K11251]
129712968  core histone macro-H2A.2-like isoform X1 [KO:K11251]
129712970  core histone macro-H2A.2-like isoform X1 [KO:K11251]
129701783  core histone macro-H2A.1 isoform X1 [KO:K11251]
129713425  histone H2A.V isoform X1 [KO:K11251]
129700522  histone H2A.Z [KO:K11251]
129712348  late histone H2A.2.2-like [KO:K11251]
129694608  histone H2AX-like [KO:K11251]
129701186  histone H2AX-like [KO:K11251]
129704666  histone H2A [KO:K11251]
129714280  histone H2A-like [KO:K11251]
129714282  histone H2AX-like [KO:K11251]
129715148  histone H2AX-like [KO:K11251]
129715197  histone H2A type 1-like [KO:K11251]
129715214  histone H2A-like [KO:K11251]
129715336  histone H2A-like [KO:K11251]
129715341  histone H2A-like [KO:K11251]
129715344  histone H2A-like [KO:K11251]
129715415  late histone H2A.L3-like [KO:K11251]
129715503  histone H2AX-like [KO:K11251]
129715926  late histone H2A.L3-like [KO:K11251]
129715927  histone H2AX-like [KO:K11251]
129716186  histone H2A-like isoform X1 [KO:K11251]
129713413  peptidyl-prolyl cis-trans isomerase-like [KO:K03767] [EC:5.2.1.8]
129712900  peptidyl-prolyl cis-trans isomerase-like [KO:K03767] [EC:5.2.1.8]
129712901  uncharacterized protein LOC129712901 [KO:K03767] [EC:5.2.1.8]
129711578  bcl2b; apoptosis regulator Bcl-2 isoform X1 [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
leri00250  Alanine, aspartate and glutamate metabolism
leri04210  Apoptosis
KO pathway
ko04217   
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