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IκB kinase ε-dependent phosphorylation and degradation of X-linked inhibitor of apoptosis sensitizes cells to virus-induced apoptosis.
- Source :
-
Journal of virology [J Virol] 2012 Jan; Vol. 86 (2), pp. 726-37. Date of Electronic Publication: 2011 Nov 09. - Publication Year :
- 2012
-
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.
- Subjects :
- Amino Acid Motifs
Cell Line
Humans
I-kappa B Kinase genetics
Phosphorylation
Respirovirus Infections virology
Sendai virus genetics
X-Linked Inhibitor of Apoptosis Protein chemistry
X-Linked Inhibitor of Apoptosis Protein genetics
Apoptosis
I-kappa B Kinase metabolism
Respirovirus Infections metabolism
Respirovirus Infections physiopathology
Sendai virus physiology
X-Linked Inhibitor of Apoptosis Protein metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1098-5514
- Volume :
- 86
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal of virology
- Publication Type :
- Academic Journal
- Accession number :
- 22072751
- Full Text :
- https://doi.org/10.1128/JVI.05989-11