Human Interaction Network Ontology

Last uploaded: June 27, 2014
Preferred Name

TRAF3 binds to TRIF:activated TLR3/4 complex
Synonyms
Definitions

has a Stoichiometric coefficient of 2 TRAF3 is a ubiquitin ligase recruited to both MYD88- and TRIF-assembled signalling complexes [Hacker H et al 2006]. However, TRAF3 controls the production of interferon and proinflammatory cytokines in different ways [Tseng PH et al 2010]. Positive or negative type of regulation is dictated by TRAF3 subcellular distribution and its mode of ubiquitination. Thus, TRIF-mediated signaling initiated on endosomes triggers TRAF3 self-ubiquitination through noncanonical (K63-linked) polyubiquitination, which is essential for activation of IRF3/7 and the interferon response. In contrast, during MyD88-dependent signaling initiated from plasma membrane TRAF3 functions as a negative regulator of inflammatory cytokines and mitogen-activated protein kinases (MAPKs), unless it undergoes degradative (K48-linked) polyubiquitination mediated by TRAF6 and a pair of the ubiquitin ligases cIAP1 and cIAP2. The degradation of TRAF3 is essential for MAPK activation via TAK1 and MEKK1 [Tseng PH et al 2010]. Reviewed: Fitzgerald, Katherine A, 2012-11-13 Authored: Shamovsky, V, 2012-04-26 Edited: Shamovsky, V, 2012-05-25 Reviewed: D'Eustachio, P, 2012-05-25

ID

http://purl.obolibrary.org/obo/HINO_0009335

comment

has a Stoichiometric coefficient of 2

TRAF3 is a ubiquitin ligase recruited to both MYD88- and TRIF-assembled signalling complexes [Hacker H et al 2006]. However, TRAF3 controls the production of interferon and proinflammatory cytokines in different ways [Tseng PH et al 2010]. Positive or negative type of regulation is dictated by TRAF3 subcellular distribution and its mode of ubiquitination. Thus, TRIF-mediated signaling initiated on endosomes triggers TRAF3 self-ubiquitination through noncanonical (K63-linked) polyubiquitination, which is essential for activation of IRF3/7 and the interferon response. In contrast, during MyD88-dependent signaling initiated from plasma membrane TRAF3 functions as a negative regulator of inflammatory cytokines and mitogen-activated protein kinases (MAPKs), unless it undergoes degradative (K48-linked) polyubiquitination mediated by TRAF6 and a pair of the ubiquitin ligases cIAP1 and cIAP2. The degradation of TRAF3 is essential for MAPK activation via TAK1 and MEKK1 [Tseng PH et al 2010].

Reviewed: Fitzgerald, Katherine A, 2012-11-13

Authored: Shamovsky, V, 2012-04-26

Edited: Shamovsky, V, 2012-05-25

Reviewed: D'Eustachio, P, 2012-05-25

definition source

Pubmed19898473

Reactome, http://www.reactome.org

Pubmed16306936

Pubmed16306937

has input

http://purl.obolibrary.org/obo/UniProt_Q13114

http://purl.obolibrary.org/obo/HINO_0005478

has output

http://purl.obolibrary.org/obo/HINO_0005475

label

TRAF3 binds to TRIF:activated TLR3/4 complex

prefixIRI

HINO:0009335

prefLabel

TRAF3 binds to TRIF:activated TLR3/4 complex

seeAlso

ReactomeREACT_121070

Reactome Database ID Release 432201338

subClassOf

http://purl.obolibrary.org/obo/INO_0000040

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