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Regulating the balance between necroptosis, apoptosis and inflammation by inhibitors of apoptosis proteins
Author(s) -
Vasilikos Lazaros,
Spilgies Lisanne M,
Knop Janin,
Wong Wendy WeiLynn
Publication year - 2017
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/icb.2016.118
Subject(s) - necroptosis , apoptosis , inflammation , microbiology and biotechnology , balance (ability) , programmed cell death , chemistry , biology , immunology , biochemistry , neuroscience
Understanding how inhibitor of apoptosis proteins (IAPs) regulate apoptosis and necroptosis has been fast‐forwarded by the use of Smac mimetics (SMs) to deplete or inhibit the IAPs, specifically cIAP1, cIAP2 and XIAP. The loss or inhibition of cIAP1, cIAP2 and XIAP causes the majority of cells to be sensitized to death receptor induced cell death, such as with tumour necrosis factor (TNF). Mouse genetics shows that there is some functional redundancy and the use of SMs has allowed us to understand how changing the composition of proteins recruited to TNF receptor 1 on TNF ligation can alter protein complex formation and activation of apoptosis or necroptosis, particularly when caspases are inhibited. Determining when or how caspase inhibition occurs physiologically combined with the loss of IAPs will be the next challenge in understanding the ability of IAPs to prevent cell death and/or limit inflammation.