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

Stable Identifier
Reaction [binding]
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-α 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
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

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

J. Biol. Chem. 2006
20385093 Crystal structures of the TRAF2: cIAP2 and the TRAF1: TRAF2: cIAP2 complexes: affinity, specificity, and regulation

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

Mol. Cell 2010
This event is regulated
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