“…As indicated by the lighter shaded complex, RIPK1 and LUBAC may be directly recruited to complex I, allowing MAPK and NF-κB activation independent of complex II formation. Understanding the ubiquitin-mediated mechanisms that result in pro-tumorigenic NF-κB activation upon TRAILR stimulation is one of the important steps towards improving the therapeutic effect of TRAILR agonists, which are currently being evaluated as anticancer drugs 179 . APC/C, anaphase-promoting complex; also known as the cyclosome; BCL-xL, also known as BCL2L1; BID, BH3, interacting domain death agonist; FBXW7, F-box/WD repeat-containing protein 7; HOIL1, haeme-oxidized IRP2 ubiquitin ligase 1 (also known as RBCK1); HOIP, HOIL1-interacting protein (also known as RNF31); NEMO, NF-κB essential modulator; P, phosphorylation; PUMA, p53 up-regulated modulator of apoptosis (also known as BBC3); SHARPIN, shank-associated RH domain-interacting protein; Ub, ubiquitin.…”