KEGG   PATHWAY: ko04623
Entry
ko04623                     Pathway                                

Name
Cytosolic DNA-sensing pathway
Description
Specific families of pattern recognition receptors are responsible for detecting foreign DNA from invading microbes or host cells and generating innate immune responses. DAI is the first identified sensor of cytosolic DNA which activates the IRF and NF-{kappa}B transcription factors, leading to production of type I interferon and other cytokines. The second type of cytoplasmic DNA sensor is AIM2. Upon sensing DNA, AIM2 triggers the assembly of the inflammasome, culminating in interleukin maturation. In addition to these receptors, there is a mechanism to sense foreign DNA, with the host RNA polymerase III converting the DNA into RNA for recognition by the RNA sensor RIG-I. These pathways provide various means to alert the cell.
Class
Organismal Systems; Immune system
Pathway map
ko04623  Cytosolic DNA-sensing pathway
ko04623

Disease
H00290  Aicardi-Goutieres syndrome
H00291  Familial chilblain lupus (FCL)
H00880  Dyschromatosis symmetrica hereditaria
H00882  Cocoon syndrome
H01000  Retinal vasculopathy with cerebral leukodystrophy
H01746  STING-associated vasculopathy with onset in infancy
Drug
D11791  Ibezapolstat (USAN)
Orthology
K03018  DNA-directed RNA polymerase III subunit RPC1 [EC:2.7.7.6]
K03021  DNA-directed RNA polymerase III subunit RPC2 [EC:2.7.7.6]
K03023  DNA-directed RNA polymerase III subunit RPC3
K03026  DNA-directed RNA polymerase III subunit RPC4
K14721  DNA-directed RNA polymerase III subunit RPC5
K03027  DNA-directed RNA polymerases I and III subunit RPAC1
K03019  DNA-directed RNA polymerase III subunit RPC11
K03020  DNA-directed RNA polymerases I and III subunit RPAC2
K03022  DNA-directed RNA polymerase III subunit RPC8
K03024  DNA-directed RNA polymerase III subunit RPC7
K03025  DNA-directed RNA polymerase III subunit RPC6
K03013  DNA-directed RNA polymerases I, II, and III subunit RPABC1
K03014  DNA-directed RNA polymerases I, II, and III subunit RPABC2
K03016  DNA-directed RNA polymerases I, II, and III subunit RPABC3
K03009  DNA-directed RNA polymerases I, II, and III subunit RPABC4
K03007  DNA-directed RNA polymerases I, II, and III subunit RPABC5
K12646  ATP-dependent RNA helicase DDX58 [EC:3.6.4.13]
K12648  mitochondrial antiviral-signaling protein
K02580  nuclear factor NF-kappa-B p105 subunit
K04735  transcription factor p65
K05405  interleukin 6
K17834  cyclic GMP-AMP synthase [EC:2.7.7.86]
K12654  transmembrane protein 173
K05410  TANK-binding kinase 1 [EC:2.7.11.10]
K07211  inhibitor of nuclear factor kappa-B kinase subunit epsilon [EC:2.7.11.10]
K05411  interferon regulatory factor 3
K09447  interferon regulatory factor 7
K05414  interferon alpha
K05415  interferon beta
K12965  Z-DNA binding protein 1
K02861  receptor-interacting serine/threonine-protein kinase 1 [EC:2.7.11.1]
K08847  receptor-interacting serine/threonine-protein kinase 3 [EC:2.7.11.1]
K07210  inhibitor of nuclear factor kappa-B kinase subunit gamma
K04467  inhibitor of nuclear factor kappa-B kinase subunit alpha [EC:2.7.11.10]
K07209  inhibitor of nuclear factor kappa-B kinase subunit beta [EC:2.7.11.10]
K02581  NF-kappa-B inhibitor beta
K04734  NF-kappa-B inhibitor alpha
K12964  C-C motif chemokine 4
K12499  C-C motif chemokine 5
K12671  C-X-C motif chemokine 10
K12966  absent in melanoma 2
K12799  apoptosis-associated speck-like protein containing a CARD
K01370  caspase 1 [EC:3.4.22.36]
K04519  interleukin 1 beta
K05482  interleukin 18
K12967  interleukin 33
K10790  three prime repair exonuclease 1 [EC:3.1.11.2]
K12968  double-stranded RNA-specific adenosine deaminase [EC:3.5.4.37]
K12969  Vaccinia virus protein E3
K12970  Murid betaherpesvirus 1 ribonucleoside-diphosphate reductase [EC:1.17.4.1]
K12971  interferon-activable protein 202
Compound
C20640  Cyclic GMP-AMP
Reference
  Authors
Yanai H, Savitsky D, Tamura T, Taniguchi T
  Title
Regulation of the cytosolic DNA-sensing system in innate immunity: a current view.
  Journal
Curr Opin Immunol 21:17-22 (2009)
DOI:10.1016/j.coi.2009.01.005
Reference
  Authors
Vilaysane A, Muruve DA
  Title
The innate immune response to DNA.
  Journal
Semin Immunol 21:208-14 (2009)
DOI:10.1016/j.smim.2009.05.006
Reference
  Authors
Takeshita F, Ishii KJ
  Title
Intracellular DNA sensors in immunity.
  Journal
Curr Opin Immunol 20:383-8 (2008)
DOI:10.1016/j.coi.2008.05.009
Reference
  Authors
Takaoka A, Shinohara S
  Title
DNA sensors in innate immune system.
  Journal
Uirusu 58:37-46 (2008)
DOI:10.2222/jsv.58.37
Reference
  Authors
Takaoka A, Taniguchi T
  Title
Cytosolic DNA recognition for triggering innate immune responses.
  Journal
Adv Drug Deliv Rev 60:847-57 (2008)
DOI:10.1016/j.addr.2007.12.002
Reference
  Authors
Kaiser WJ, Upton JW, Mocarski ES
  Title
Receptor-interacting protein homotypic interaction motif-dependent control of NF-kappa B activation via the DNA-dependent activator of IFN regulatory factors.
  Journal
J Immunol 181:6427-34 (2008)
DOI:10.4049/jimmunol.181.9.6427
Reference
  Authors
Rebsamen M, Heinz LX, Meylan E, Michallet MC, Schroder K, Hofmann K, Vazquez J, Benedict CA, Tschopp J
  Title
DAI/ZBP1 recruits RIP1 and RIP3 through RIP homotypic interaction motifs to activate NF-kappaB.
  Journal
EMBO Rep 10:916-22 (2009)
DOI:10.1038/embor.2009.109
Reference
  Authors
Wang Z, Choi MK, Ban T, Yanai H, Negishi H, Lu Y, Tamura T, Takaoka A, Nishikura K, Taniguchi T
  Title
Regulation of innate immune responses by DAI (DLM-1/ZBP1) and other DNA-sensing molecules.
  Journal
Proc Natl Acad Sci U S A 105:5477-82 (2008)
DOI:10.1073/pnas.0801295105
Reference
  Authors
Stetson DB, Ko JS, Heidmann T, Medzhitov R
  Title
Trex1 prevents cell-intrinsic initiation of autoimmunity.
  Journal
Cell 134:587-98 (2008)
DOI:10.1016/j.cell.2008.06.032
Reference
  Authors
Schroder K, Muruve DA, Tschopp J
  Title
Innate immunity: cytoplasmic DNA sensing by the AIM2 inflammasome.
  Journal
Curr Biol 19:R262-5 (2009)
DOI:10.1016/j.cub.2009.02.011
Reference
  Authors
Krieg AM
  Title
AIMing 2 detect foreign DNA.
  Journal
Sci Signal 2:pe39 (2009)
DOI:10.1126/scisignal.277pe39
Reference
  Authors
O'Neill LA
  Title
DNA makes RNA makes innate immunity.
  Journal
Cell 138:428-30 (2009)
DOI:10.1016/j.cell.2009.07.021
Reference
  Authors
Ishii KJ, Coban C, Kato H, Takahashi K, Torii Y, Takeshita F, Ludwig H, Sutter G, Suzuki K, Hemmi H, Sato S, Yamamoto M, Uematsu S, Kawai T, Takeuchi O, Akira S
  Title
A Toll-like receptor-independent antiviral response induced by double-stranded B-form DNA.
  Journal
Nat Immunol 7:40-8 (2006)
DOI:10.1038/ni1282
Reference
  Authors
Cao X
  Title
New DNA-sensing pathway feeds RIG-I with RNA.
  Journal
Nat Immunol 10:1049-51 (2009)
DOI:10.1038/ni1009-1049
Reference
  Authors
Sun L, Wu J, Du F, Chen X, Chen ZJ
  Title
Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway.
  Journal
Science 339:786-91 (2013)
DOI:10.1126/science.1232458
Related
pathway
ko04064  NF-kappa B signaling pathway
ko04120  Ubiquitin mediated proteolysis
ko04622  RIG-I-like receptor signaling pathway
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