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Ubiquitylated Tax targets and binds the IKK signalosome at the centrosome

Oncogene volume 27, pages 1665–1676 (2008)Cite this article

Abstract

Constitutive activation of the NF-κB pathway by the Tax oncoprotein plays a crucial role in the proliferation and transformation of HTLV-I infected T lymphocytes. We have previously shown that Tax ubiquitylation on C-terminal lysines is critical for binding of Tax to IκB kinase (IKK) and its subsequent activation. Here, we report that ubiquitylated Tax is not associated with active cytosolic IKK subunits, but binds endogenous IKK-α, -β, -γ, targeting them to the centrosome. K63-ubiquitylated Tax colocalizes at the centrosome with IKK-γ, while K48-ubiquitylated Tax is stabilized upon proteasome inhibition. Altogether, these results support a model in which K63-ubiquitylated Tax activates IKK in a centrosome-associated signalosome, leading to the production of Tax-free active cytoplasmic IKK. These observations highlight an unsuspected link between Tax-induced IKK activation and the centrosome.

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Acknowledgements

We thank Pierre Bourdoncle (Institut Cochin) for confocal analysis. The imagery department of the Institut Universitaire d'Hématologie IFR105 is supported by grants from the Conseil Regional d'Ile-de-France and the Ministère de la Recherche.

This work was supported by the American University of Beirut Medical Practice Plan and University Research Board, the Lebanese National Council for Scientific Research, the CNRS contrat PICS and the Fondation de France.

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Author notes

  1. R Nasr and A Favre-Bonvin: These two authors contributed equally to this work.

Authors and Affiliations

  1. Department of Internal Medicine, American University of Beirut, Beirut, Lebanon

    Y Kfoury, R Nasr, H El Hajj, A G Mikati & A Bazarbachi

  2. UMR 7151 CNRS, Laboratoire Associé au Comité de Paris de la Ligue contre le Cancer, Paris, France

    R Nasr, N Renault, M-L Giron, A Saib & H de Thé

  3. Département de Biologie Cellulaire, UMR 7151 CNRS/Université Paris 7, INSERM U567, Université Paris 5, Faculté de Médecine René Descartes, UMR3, Institut Cochin, Paris, France

    A Favre-Bonvin, E Chiari & C Pique

  4. Department of Human Morphology, American University of Beirut, Beirut, Lebanon

    M El-Sabban

  5. Imagery Department of the Institut Universitaire d'Hématologie IFR105, Paris, France

    N Setterblad

  6. CNRS UMR 8603 and Department of Hematology, Necker Hospital, Paris, France

    O Hermine

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  1. Y Kfoury
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Corresponding author

Correspondence to A Bazarbachi.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Kfoury, Y., Nasr, R., Favre-Bonvin, A. et al. Ubiquitylated Tax targets and binds the IKK signalosome at the centrosome. Oncogene 27, 1665–1676 (2008). https://doi.org/10.1038/sj.onc.1210804

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