Regulating the balance between necroptosis, apoptosis and inflammation by inhibitors of apoptosis proteins.

Abstract:

: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.

journal_name

Immunol Cell Biol

authors

Vasilikos L,Spilgies LM,Knop J,Wong WW

doi

10.1038/icb.2016.118

subject

Has Abstract

pub_date

2017-02-01 00:00:00

pages

160-165

issue

2

eissn

0818-9641

issn

1440-1711

pii

icb2016118

journal_volume

95

pub_type

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