Ubiquitin-regulated recruitment of IkappaB kinase epsilon to the MAVS interferon signaling adapter
| Autor: | Paz, Suzanne, Vilasco, Myriam, Arguello, Meztli, Sun, Qiang, Lacoste, Judith, Nguyen, Thi Lien-Anh, Zhao, Tiejun, Shestakova, Elena A., Zaari, Scott, Bibeau-Poirier, Annie, Servant, Marc J., Lin, Rongtuan, Meurs, Eliane F., Hiscott, John |
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| Přispěvatelé: | Terry Fox Molecular Oncology Group, Lady Davis Institute for Medical Research, Department of Microbiology and Immunology [Montréal], McGill University = Université McGill [Montréal, Canada], Département de Virologie - Department of Virology, Institut Pasteur [Paris], Faculté de Pharmacie [Montréal], Université de Montréal (UdeM), Hépacivirus et immunité innée, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Department of Medecine [Montréal], Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
MESH: Signal Transduction
MESH: Ubiquitin MESH: Mitochondria MESH: NF-kappa B Protein Serine-Threonine Kinases Sendai virus MESH: Protein-Serine-Threonine Kinases Cell Line MESH: Recombinant Proteins Chlorocebus aethiops Protein Interaction Mapping MESH: RNA Small Interfering Animals Humans MESH: Animals MESH: Lysine MESH: I-kappa B Kinase RNA Small Interfering Adaptor Proteins Signal Transducing MESH: Adaptor Proteins Signal Transducing MESH: Humans MESH: Interferon-beta Ubiquitin Lysine MESH: Protein Interaction Mapping NF-kappa B MESH: Sendai virus Interferon-beta Articles MESH: Cercopithecus aethiops Recombinant Proteins I-kappa B Kinase Mitochondria MESH: Cell Line MESH: COS Cells MESH: Hela Cells MESH: Mutagenesis Site-Directed [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology COS Cells Mutagenesis Site-Directed HeLa Cells Signal Transduction |
| Zdroj: | Molecular and Cellular Biology Molecular and Cellular Biology, American Society for Microbiology, 2009, 29 (12), pp.3401-12. ⟨10.1128/MCB.00880-08⟩ Molecular and Cellular Biology, 2009, 29 (12), pp.3401-12. ⟨10.1128/MCB.00880-08⟩ |
| ISSN: | 0270-7306 1098-5549 |
| DOI: | 10.1128/MCB.00880-08⟩ |
| Popis: | International audience; Induction of the antiviral interferon response is initiated upon recognition of viral RNA structures by the RIG-I or Mda-5 DEX(D/H) helicases. A complex signaling cascade then converges at the mitochondrial adapter MAVS, culminating in the activation of the IRF and NF-kappaB transcription factors and the induction of interferon gene expression. We have previously shown that MAVS recruits IkappaB kinase epsilon (IKKepsilon) but not TBK-1 to the mitochondria following viral infection. Here we map the interaction of MAVS and IKKepsilon to the C-terminal region of MAVS and demonstrate that this interaction is ubiquitin dependent. MAVS is ubiquitinated following Sendai virus infection, and K63-linked ubiquitination of lysine 500 (K500) of MAVS mediates recruitment of IKKepsilon to the mitochondria. Real-time PCR analysis reveals that a K500R mutant of MAVS increases the mRNA level of several interferon-stimulated genes and correlates with increased NF-kappaB activation. Thus, recruitment of IKKepsilon to the mitochondria upon MAVS K500 ubiquitination plays a modulatory role in the cascade leading to NF-kappaB activation and expression of inflammatory and antiviral genes. These results provide further support for the differential role of IKKepsilon and TBK-1 in the RIG-I/Mda5 pathway. |
| Databáze: | OpenAIRE |
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