TNF:TNFR1:TRADD:TRAF2:RIPK1 recruits BIRC2/3 (cIAP1/2)

Stable Identifier
R-HSA-5357780
Type
Reaction [binding]
Species
Homo sapiens
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Activation of tumor necrosis factor receptor 1 (TNFR1) stimulates the formation of complex that consists of TNFR1, TNFR-associated via death domain (TRADD), RIPK1, TNFR-associated factor 2 (TRAF2) and cellular inhibitor of apoptosis (BIRC2/3 also known as cIAP1/2). TRAF2 and BIRC (cIAP1) were found to form a complex in solution (Zheng et al. 2010), suggesting that TNFR1:TRADD:RIPK1 receptor complex recruits the TRAF2:BIRC complex. Following TNF-alpha stimulation, RIPK1 is promptly K63-ubiquitinated at Lys377 residue by E3 ubiquitin ligases, such as BIRC2/3, to allow recruitment of the TAB2:TAK1 complex, the LUBAC and the IKK complex and eventually to stimulate the canonical NFkB activation.

Literature References
PubMed ID Title Journal Year
20385093 Crystal structures of the TRAF2: cIAP2 and the TRAF1: TRAF2: cIAP2 complexes: affinity, specificity, and regulation

Zheng, C, Kabaleeswaran, V, Wang, Y, Cheng, G, Wu, H

Mol. Cell 2010
16282325 Distinct BIR domains of cIAP1 mediate binding to and ubiquitination of tumor necrosis factor receptor-associated factor 2 and second mitochondrial activator of caspases

Samuel, T, Welsh, K, Lober, T, Togo, SH, Zapata, JM, Reed, JC

J. Biol. Chem. 2006
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