KEGG PATHWAY: ko04623

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

Module

M00181

RNA polymerase III, eukaryotes [PATH:ko04623]

Disease

H00290	Aicardi-Goutieres Syndrome (AGS)
H00291	Familial chilblain lupus (FCL)
H00880	Dyschromatosis symmetrica hereditaria
H00882	Cocoon syndrome
H01000	Retinal vasculopathy with cerebral leukodystrophy (RVCL)

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 RPC10
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:3.6.3.14]
K12648	mitochondrial antiviral-signaling protein
K02580	nuclear factor NF-kappa-B p105 subunit
K04735	transcription factor p65
K05405	interleukin 6
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.-]
K12969	protein E3
K12970	ribonucleoside-diphosphate reductase [EC:1.17.4.1]
K12971	interferon-activable protein 202

Reference

PMID:19362700

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)

Reference

PMID:19497760

Authors

Vilaysane A, Muruve DA

Title

The innate immune response to DNA.

Journal

Semin Immunol 21:208-14 (2009)

Reference

PMID:18573338

Authors

Takeshita F, Ishii KJ

Title

Intracellular DNA sensors in immunity.

Journal

Curr Opin Immunol 20:383-8 (2008)

Reference

PMID:19122387

Authors

Takaoka A, Shinohara S

Title

DNA sensors in innate immune system.

Journal

Uirusu 58:37-46 (2008)

Reference

PMID:18280611

Authors

Takaoka A, Taniguchi T

Title

Cytosolic DNA recognition for triggering innate immune responses.

Journal

Adv Drug Deliv Rev 60:847-57 (2008)

Reference

PMID:18941233

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)

Reference

PMID:19590578

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)

Reference

PMID:18375758

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)

Reference

PMID:18724932

Authors

Stetson DB, Ko JS, Heidmann T, Medzhitov R

Title

Trex1 prevents cell-intrinsic initiation of autoimmunity.

Journal

Cell 134:587-98 (2008)

Reference

PMID:19321146

Authors

Schroder K, Muruve DA, Tschopp J

Title

Innate immunity: cytoplasmic DNA sensing by the AIM2 inflammasome.

Journal

Curr Biol 19:R262-5 (2009)

Reference

PMID:19567913

Authors

Krieg AM

Title

AIMing 2 detect foreign DNA.

Journal

Sci Signal 2:pe39 (2009)

Reference

PMID:19665965

Authors

O'Neill LA

Title

DNA makes RNA makes innate immunity.

Journal

Cell 138:428-30 (2009)

Reference

PMID:16286919

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)

Reference

PMID:19767723

Authors

Cao X

Title

New DNA-sensing pathway feeds RIG-I with RNA.

Journal

Nat Immunol 10:1049-51 (2009)

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Ontology (1)   
   KEGG BRITE (1)   
Pathway (4)   
   KEGG PATHWAY (2)   
   KEGG MODULE (1)   
   BioSystems (1)   
Disease (5)   
   KEGG DISEASE (5)   
Chemical reaction (8)   
   KEGG ENZYME (8)   
Gene (50)   
   KEGG ORTHOLOGY (50)   
Literature (14)   
   PubMed (14)   
All databases (82)   

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