This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Google Scholar
Right arrow Articles by Paz, S.
Right arrow Articles by Hiscott, J.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Paz, S.
Right arrow Articles by Hiscott, J.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, June 2009, p. 3401-3412, Vol. 29, No. 12
0270-7306/09/$08.00+0     doi:10.1128/MCB.00880-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Ubiquitin-Regulated Recruitment of I{kappa}B Kinase {varepsilon} to the MAVS Interferon Signaling Adapter{triangledown} ,{dagger}

Suzanne Paz,1,2,{ddagger} Myriam Vilasco,4,{ddagger} Meztli Arguello,1 Qiang Sun,1 Judith Lacoste,1 Thi Lien-Anh Nguyen,1,2 Tiejun Zhao,1 Elena A. Shestakova,1 Scott Zaari,2 Annie Bibeau-Poirier,5 Marc J. Servant,5 Rongtuan Lin,1,2 Eliane F. Meurs,4 and John Hiscott1,2,3*

Terry Fox Molecular Oncology Group, Lady Davis Institute, Jewish General Hospital, Montreal, Canada H3T 1E2,1 Departments of Microbiology & Immunology,2 Medicine, McGill University, Montreal, Canada,3 Department of Virology, Institut Pasteur, Paris, France,4 Faculté de Pharmacie, Université de Montréal, Montreal, Canada5

Received 3 June 2008/ Returned for modification 22 July 2008/ Accepted 19 March 2009

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-{kappa}B transcription factors and the induction of interferon gene expression. We have previously shown that MAVS recruits I{kappa}B kinase {varepsilon} (IKK{varepsilon}) but not TBK-1 to the mitochondria following viral infection. Here we map the interaction of MAVS and IKK{varepsilon} 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 IKK{varepsilon} 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-{kappa}B activation. Thus, recruitment of IKK{varepsilon} to the mitochondria upon MAVS K500 ubiquitination plays a modulatory role in the cascade leading to NF-{kappa}B activation and expression of inflammatory and antiviral genes. These results provide further support for the differential role of IKK{varepsilon} and TBK-1 in the RIG-I/Mda5 pathway.

* Corresponding author. Mailing address: Lady Davis Institute for Medical Research, 3755 Cote Ste. Catherine, Montreal, Quebec, Canada H3T 1E2. Phone: (514) 340-8222, ext. 5265. Fax: (514) 340-7576. E-mail: john.hiscott{at}mcgill.ca

{triangledown} Published ahead of print on 20 April 2009.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

{ddagger} S.P. and M.V. contributed equally to this work.

Molecular and Cellular Biology, June 2009, p. 3401-3412, Vol. 29, No. 12
0270-7306/09/$08.00+0     doi:10.1128/MCB.00880-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Vitour, D., Dabo, S., Ahmadi Pour, M., Vilasco, M., Vidalain, P.-O., Jacob, Y., Mezel-Lemoine, M., Paz, S., Arguello, M., Lin, R., Tangy, F., Hiscott, J., Meurs, E. F. (2009). Polo-like Kinase 1 (PLK1) Regulates Interferon (IFN) Induction by MAVS. J. Biol. Chem. 284: 21797-21809 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»