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.
Zapata, JM, Lober, T, Welsh, K, Reed, JC, Togo, SH, Samuel, T
Wang, Y, Wu, H, Zheng, C, Cheng, G, Kabaleeswaran, V
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