IAPs and Necroptotic Cell Death
The word “necroptosis” refers to a mechanism for cell suicide that does not require caspase activity or the proapoptotic Bcl-2 family members Bax and Bak. It can be triggered following ligation of certain members of the TNF receptor superfamily that activate a pathway involving proteins such as the RIP kinases and the pseudokinase MLKL. Signalling by this pathway is modulated by other proteins, such as the TNF receptor-associated factors (TRAFs) and the inhibitor of apoptosis proteins (IAPs). cIAPs interact with TRAFs, ubiquitylate RIP kinases and thereby promote activation of canonical NF-κB by TNF receptors and regulate RIP kinase levels at signalling complexes. “Smac-mimetic” compounds antagonise cIAPs to promote cell death by both caspase-dependent apoptotic and caspase-independent necroptotic mechanisms.
KeywordsEmbryonic Lethality Ubiquitin Chain Cell Death Inhibitor Extrinsic Apoptosis Pathway TNFR1 Signalling
This work was funded by NHMRC grants 1025594 and 1046984 and made possible through Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS (361646).
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