TNF:TNFR1 binds TRADD, TRAF2 and RIPK1
Species Homo sapiens
Once the TNF-alpha:TNFR1:TRADD:RIPK1 complex has been formed there is concomitant recruitment of TRAF2, BIRC2/3 (cIAP1/2) and then of the TAB2:TAK1 and the IKK complex. TRAF2 and BIRC (cIAP1) were found to form a complex in solution (Zheng C et al. 2010), suggesting that TNFR1:TRADD:RIPK1 receptor complex recruits the TRAF2:BIRC complex as a whole. However, the expression levels of BIRCs are typically lower compared to TRAF2 suggesting that TNF-stimulated TNFR1 complex may also recruit TRAF2 alone. RIPK1 and the TRAF2:cIAP1/2 can be released from TNFR1 receptor complex in a poorly understood process associated with internalization and after that there is the formation of a so called complex II containing the adapter protein FADD, caspase-8 and RIPK1. Complex II has the potential to activate caspase-8 (Micheau O & Tschopp J 2003). The steps leading to the JUN, NF kappaB or apoptotic pathways are rife with opportunities for modulation.
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