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J Virol. 2012 Jan;86(2):726-37. doi: 10.1128/JVI.05989-11. Epub 2011 Nov 9.

IκB kinase ε-dependent phosphorylation and degradation of X-linked inhibitor of apoptosis sensitizes cells to virus-induced apoptosis.

Author information

1
Terry Fox Molecular Oncology Group, Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montreal, Canada.

Abstract

X-linked inhibitor of apoptosis (XIAP) is a potent antagonist of caspase 3-, 7-, and 9-dependent apoptotic activities that functions as an E3 ubiquitin ligase, and it targets caspases for degradation. In this study, we demonstrate that Sendai virus (SeV) infection results in the IKKε- or TBK1-mediated phosphorylation of XIAP in vivo at Ser430, resulting in Lys(48)-linked autoubiquitination at Lys322/328 residues, followed by the subsequent proteasomal degradation of XIAP. Interestingly, IKKε expression and XIAP turnover increases SeV-triggered mitochondrion-dependent apoptosis via the release of caspase 3, whereas TBK1 expression does not increase apoptosis. Interestingly, phosphorylation also regulates XIAP interaction with the transcription factor IRF3, suggesting a role in IRF3-Bax-mediated apoptosis. Our findings reveal a novel function of IKKε as a regulator of the virus-induced triggering of apoptosis via the phosphorylation-dependent turnover of XIAP.

PMID:
22072751
PMCID:
PMC3255812
DOI:
10.1128/JVI.05989-11
[Indexed for MEDLINE]
Free PMC Article
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