IAPs and Necroptotic Cell Death

  • John SilkeEmail author
  • David Vaux
Part of the Cell Death in Biology and Diseases book series (CELLDEATH)


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.


Embryonic Lethality Ubiquitin Chain Cell Death Inhibitor Extrinsic Apoptosis Pathway TNFR1 Signalling 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



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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© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.The Walter and Eliza Hall Institute of Medical ResearchParkvilleAustralia
  2. 2.Department of Medical BiologyUniversity of MelbourneParkvilleAustralia

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