I B Kinase -Dependent Phosphorylation and Degradation of X-Linked Inhibitor of Apoptosis Sensitizes Cells to Virus-Induced Apoptosis

Terry Fox Molecular Oncology Group, Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montreal, Canada.
Journal of Virology (Impact Factor: 4.44). 11/2011; 86(2):726-37. DOI: 10.1128/JVI.05989-11
Source: PubMed


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 Lys48-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.

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