Involvement of the ubiquitin-like domain of TBK1/IKK-i kinases in regulation of IFN-inducible genes

Fumiyo Ikeda, Christina Maria Hecker, Alexis Rozenknop, Rolf Dietrich Nordmeier, Vladimir Rogov, Kay Hofmann, Shizuo Akira, Volker Dötsch, Ivan Dikic

Research output: Contribution to journalArticle

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Abstract

TANK-binding kinase 1 (TBK1/NAK/T2K) and I-κB Kinase (IKK-i/IKK-ε) play important roles in the regulation of interferon (IFN)-inducible genes during the immune response to bacterial and viral infections. Cell stimulation with ssRNA virus, dsDNA virus or gram-negative bacteria leads to activation of TBK1 or IKK-i, which in turn phosphorylates the transcription factors, IFN-regulatory factor (IRF) 3 and IRF7, promoting their translocation in the nucleus. To understand the molecular basis of activation of TBK1, we analyzed the sequence of TBK1 and IKK-i and identified a ubiquitin-like domain (ULD) adjacent to their kinase domains. Deletion or mutations of the ULD in TBK1 or IKK-i impaired activation of respective kinases, failed to induce IRF3 phosphorylation and nuclear localization and to activate IFN-β or RANTES promoters. The importance of the ULD of TBK1 in LPS- or poly(I:C)-stimulated IFN-β production was demonstrated by reconstitution experiments in TBK1-IKK-i-deficient cells. We propose that the ULD is a regulatory component of the TBK1/IKK-i kinases involved in the control of the kinase activation, substrate presentation and downstream signaling pathways.

Original languageEnglish
Pages (from-to)3451-3462
Number of pages12
JournalEMBO Journal
Volume26
Issue number14
DOIs
Publication statusPublished - Jul 25 2007
Externally publishedYes

Fingerprint

Ubiquitin
Interferons
Phosphotransferases
Genes
Chemical activation
Viruses
Interferon Regulatory Factor-3
Poly I-C
Chemokine CCL5
Phosphorylation
Sequence Deletion
Virus Diseases
Gram-Negative Bacteria
Bacterial Infections
Bacteria
Transcription Factors
Substrates
Experiments

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Ikeda, F., Hecker, C. M., Rozenknop, A., Nordmeier, R. D., Rogov, V., Hofmann, K., ... Dikic, I. (2007). Involvement of the ubiquitin-like domain of TBK1/IKK-i kinases in regulation of IFN-inducible genes. EMBO Journal, 26(14), 3451-3462. https://doi.org/10.1038/sj.emboj.7601773

Involvement of the ubiquitin-like domain of TBK1/IKK-i kinases in regulation of IFN-inducible genes. / Ikeda, Fumiyo; Hecker, Christina Maria; Rozenknop, Alexis; Nordmeier, Rolf Dietrich; Rogov, Vladimir; Hofmann, Kay; Akira, Shizuo; Dötsch, Volker; Dikic, Ivan.

In: EMBO Journal, Vol. 26, No. 14, 25.07.2007, p. 3451-3462.

Research output: Contribution to journalArticle

Ikeda, F, Hecker, CM, Rozenknop, A, Nordmeier, RD, Rogov, V, Hofmann, K, Akira, S, Dötsch, V & Dikic, I 2007, 'Involvement of the ubiquitin-like domain of TBK1/IKK-i kinases in regulation of IFN-inducible genes', EMBO Journal, vol. 26, no. 14, pp. 3451-3462. https://doi.org/10.1038/sj.emboj.7601773
Ikeda, Fumiyo ; Hecker, Christina Maria ; Rozenknop, Alexis ; Nordmeier, Rolf Dietrich ; Rogov, Vladimir ; Hofmann, Kay ; Akira, Shizuo ; Dötsch, Volker ; Dikic, Ivan. / Involvement of the ubiquitin-like domain of TBK1/IKK-i kinases in regulation of IFN-inducible genes. In: EMBO Journal. 2007 ; Vol. 26, No. 14. pp. 3451-3462.
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