| IKK{varepsilon} DEPENDENT PHOSPHORYLATION AND DEGRADATION OF X-LINKED INHIBITOR OF APOPTOSIS SENSITIZES CELLS TO VIRUS-INDUCED APOPTOSIS. | |
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MedLine Citation:
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PMID: 22072751 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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 targets caspases for degradation. In this study, we demonstrate that Sendai virus (SeV) infection results in IKKε or TBK1-mediated phosphorylation of XIAP in vivo at Ser430, resulting in Lys(48)-linked autoubiquitination at Lys322/328 residues, followed by subsequent proteasomal degradation of XIAP. Interesting, IKKε expression and XIAP turnover increases SeV-triggered mitochondrial dependent apoptosis via 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 virus-induced triggering of apoptosis via phosphorylation-dependent turnover of XIAP. |
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Authors:
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Peyman Nakhaei; Qiang Sun; Mayra Solis; Thibault Mesplede; Eric Bonneil; Suzanne Paz; Rongtuan Lin; John Hiscott |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-11-9 |
Journal Detail:
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Title: Journal of virology Volume: - ISSN: 1098-5514 ISO Abbreviation: - Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-11-10 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0113724 Medline TA: J Virol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Terry Fox Molecular Oncology Group, Lady Davis Institute for Medical Research, Jewish General Hospital. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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