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IAPs and Necroptotic Cell Death

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Necrotic Cell Death

Part of the book series: Cell Death in Biology and Diseases ((CELLDEATH))

Abstract

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.

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Acknowledgements

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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Authors and Affiliations

  1. The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia

    John Silke & David Vaux

  2. Department of Medical Biology, University of Melbourne, Parkville, VIC, 3050, Australia

    John Silke & David Vaux

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  1. John Silke
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  2. David Vaux
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Correspondence to John Silke .

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Editors and Affiliations

  1. Department of Physiology, National University of Singapore Yong Loo Lin School of Medicine, Singapore, Singapore

    Han-Ming Shen

  2. Department of Biomedical Molecular Biology (UGent), VIB/University of Ghent Inflammation Research Center (VIB), Zwijnaarde, Belgium

    Peter Vandenabeele

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Silke, J., Vaux, D. (2014). IAPs and Necroptotic Cell Death. In: Shen, HM., Vandenabeele, P. (eds) Necrotic Cell Death. Cell Death in Biology and Diseases. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4614-8220-8_4

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