| Autor: |
Paz, Suzanne, Vilasco, Myriam, Arguello, Meztli, Qiang Sun, Lacoste, Judith, Thi Lien-Anh Nguyen, Tiejun Zhao, Shestakova, Elena A., Zaari, Scott, Bibeau-Poirier, Annie, Servant, Marc J., Rongtuan Lin, Meurs, Eliane F., Hiscott, John |
| Předmět: |
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| Zdroj: |
Molecular & Cellular Biology; Jun2009, Vol. 29 Issue 12, p15-15, 1p |
| Abstrakt: |
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-κB transcription factors and the induction of interferon gene expression. We have previously shown that MAVS recruits IκB kinaseϵ (IKKϵ) but not TBK-1 to the mitochondria following viral infection. Here we map the interaction of MAVS and IKKϵ 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 IKKϵ 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-κB activation. Thus, recruitment of IKKϵ to the mitochondria upon MAVS K500 ubiquitination plays a modulatory role in the cascade leading to NF-κB activation and expression of inflammatory and antiviral genes. These results provide further support for the differential role of IKKϵ and TBK-1 in the RIG-I/Mda5 pathway. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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