title: IκB kinase ε-dependent phosphorylation and degradation of X-linked inhibitor of apoptosis sensitizes cells to virus-induced apoptosis.
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.
authors.affiliation: Terry Fox Molecular Oncology Group, Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montreal, Canada.
authors.forename: Peyman
authors.initials: P
authors.lastname: Nakhaei
authors.forename: Qiang
authors.initials: Q
authors.lastname: Sun
authors.forename: Mayra
authors.initials: M
authors.lastname: Solis
authors.forename: Thibault
authors.initials: T
authors.lastname: Mesplede
authors.forename: Eric
authors.initials: E
authors.lastname: Bonneil
authors.forename: Suzanne
authors.initials: S
authors.lastname: Paz
authors.forename: Rongtuan
authors.initials: R
authors.lastname: Lin
authors.forename: John
authors.initials: J
authors.lastname: Hiscott
mesh_terms: D020816:Amino Acid Motifs; D017209:Apoptosis; D002460:Cell Line; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D010253:Respirovirus Infections / Q000378:metabolism* / Q000503:physiopathology* / Q000821:virology; D029082:Sendai virus / Q000235:genetics / Q000502:physiology*; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; D051550:I-kappa B Kinase
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