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MEETING ABSTRACT Open Access Predominant role of Tax sumoylation in Tax-induced NF-kB activation in T cells Amandine Bonnet 1,2,3* , Arnaud Favre-Bonvin 1,2,3 , Patrycja Nzounza 1,2,3 , Martine Nedelec 1,2,3 , Maxime Chazal 1,2,3 , Laetitia Waast 1,2,3 , Voahangy Randrianarison 1,2,3 , Ali Bazarbachi 4 , Renaud Mahieux 5 , Laurence Benit 1,2,3 , Claudine Pique 1,2,3 From 15th International Conference on Human Retroviruses: HTLV and Related Viruses Leuven and Gembloux, Belgium. 5-8 June 2011 Tax is a powerful activator of the NF-kB pathway, a property that is required for HTLV-1-induced T cell immortalization. Tax activates the NF-kB pathway by acting both at cytoplasmic and nuclear levels. In the cytoplasm, Tax binds to and activates the IkB Kinase (IKK) complex while in the nucleus, Tax assembles tran- scriptional active nuclear bodies. Others and we have previously demonstrated that the cytoplasmic/nuclear partition and NF-kB activity of Tax critically depend on its post-translational modifications. NEMO binding and IKK activation in the cytoplasm depends on Tax ubiqui- tination while Tax SUMOylation facilitates Tax nuclear body formation. Based on these findings, the current view is thatTax ubiquitination and SUMOylation coop- erate to ensure optimal NF-kB activation by successively regulating the cytoplasmic and nuclear events. However, many questions remain regarding the individual proper- ties of ubiquitinated or SUMOylated Tax and how the intracellular trafficking of Tax is coordinated to NF-kB activation. To explore these issues, we took advantage of the isolation of new Tax mutants that are ubiquitinated but poorly SUMOylated. We found that lack of SUMOylation modifies neither Tax stability nor Tax ubiquitination. In addition, while absence of SUMOyla- tion prevents Tax nuclear body formation, this does not preclude Tax import into the nucleus. Finally, absence of SUMOylation reduces the NF-kB activity of Tax by around 70% in T cells. We are currently investigating the effect of fusion to SUMO isoforms on the activity of the mutants. Based on these new findings, we will pro- pose a refined model for Tax-induced NF-kB activation in T cells. Author details 1 INSERM, U1016, Institut Cochin, Paris, 75014, France. 2 CNRS UMR 8104, Institut Cochin, Paris, 75014, France. 3 Univ Paris Descartes, Paris, France. 4 Department of Internal Medicine, American University of Beirut, Beirut, Lebanon. 5 INSERM, U758, Ecole Normale Supérieure de Lyon, Lyon, France. Published: 6 June 2011 doi:10.1186/1742-4690-8-S1-A132 Cite this article as: Bonnet et al.: Predominant role of Tax sumoylation in Tax-induced NF-kB activation in T cells. Retrovirology 2011 8(Suppl 1): A132. Submit your next manuscript to BioMed Central and take full advantage of: Convenient online submission Thorough peer review No space constraints or color figure charges Immediate publication on acceptance Inclusion in PubMed, CAS, Scopus and Google Scholar Research which is freely available for redistribution Submit your manuscript at www.biomedcentral.com/submit * Correspondence: [email protected] 1 INSERM, U1016, Institut Cochin, Paris, 75014, France Full list of author information is available at the end of the article Bonnet et al. Retrovirology 2011, 8(Suppl 1):A132 http://www.retrovirology.com/content/8/S1/A132 © 2011 Bonnet et al; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Predominant role of Tax sumoylation in Tax-induced NF-kB activation in T cells

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MEETING ABSTRACT Open Access

Predominant role of Tax sumoylation inTax-induced NF-kB activation in T cellsAmandine Bonnet1,2,3*, Arnaud Favre-Bonvin1,2,3, Patrycja Nzounza1,2,3, Martine Nedelec1,2,3, Maxime Chazal1,2,3,Laetitia Waast1,2,3, Voahangy Randrianarison1,2,3, Ali Bazarbachi4, Renaud Mahieux5, Laurence Benit1,2,3,Claudine Pique1,2,3

From 15th International Conference on Human Retroviruses: HTLV and Related VirusesLeuven and Gembloux, Belgium. 5-8 June 2011

Tax is a powerful activator of the NF-kB pathway, aproperty that is required for HTLV-1-induced T cellimmortalization. Tax activates the NF-kB pathway byacting both at cytoplasmic and nuclear levels. In thecytoplasm, Tax binds to and activates the IkB Kinase(IKK) complex while in the nucleus, Tax assembles tran-scriptional active nuclear bodies. Others and we havepreviously demonstrated that the cytoplasmic/nuclearpartition and NF-kB activity of Tax critically depend onits post-translational modifications. NEMO binding andIKK activation in the cytoplasm depends on Tax ubiqui-tination while Tax SUMOylation facilitates Tax nuclearbody formation. Based on these findings, the currentview is thatTax ubiquitination and SUMOylation coop-erate to ensure optimal NF-kB activation by successivelyregulating the cytoplasmic and nuclear events. However,many questions remain regarding the individual proper-ties of ubiquitinated or SUMOylated Tax and how theintracellular trafficking of Tax is coordinated to NF-kBactivation. To explore these issues, we took advantage ofthe isolation of new Tax mutants that are ubiquitinatedbut poorly SUMOylated. We found that lack ofSUMOylation modifies neither Tax stability nor Taxubiquitination. In addition, while absence of SUMOyla-tion prevents Tax nuclear body formation, this does notpreclude Tax import into the nucleus. Finally, absenceof SUMOylation reduces the NF-kB activity of Tax byaround 70% in T cells. We are currently investigatingthe effect of fusion to SUMO isoforms on the activity ofthe mutants. Based on these new findings, we will pro-

pose a refined model for Tax-induced NF-kB activationin T cells.

Author details1INSERM, U1016, Institut Cochin, Paris, 75014, France. 2CNRS UMR 8104,Institut Cochin, Paris, 75014, France. 3Univ Paris Descartes, Paris, France.4Department of Internal Medicine, American University of Beirut, Beirut,Lebanon. 5INSERM, U758, Ecole Normale Supérieure de Lyon, Lyon, France.

Published: 6 June 2011

doi:10.1186/1742-4690-8-S1-A132Cite this article as: Bonnet et al.: Predominant role of Tax sumoylationin Tax-induced NF-kB activation in T cells. Retrovirology 2011 8(Suppl 1):A132.

Submit your next manuscript to BioMed Centraland take full advantage of:

• Convenient online submission

• Thorough peer review

• No space constraints or color figure charges

• Immediate publication on acceptance

• Inclusion in PubMed, CAS, Scopus and Google Scholar

• Research which is freely available for redistribution

Submit your manuscript at www.biomedcentral.com/submit

* Correspondence: [email protected], U1016, Institut Cochin, Paris, 75014, FranceFull list of author information is available at the end of the article

Bonnet et al. Retrovirology 2011, 8(Suppl 1):A132http://www.retrovirology.com/content/8/S1/A132

© 2011 Bonnet et al; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative CommonsAttribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction inany medium, provided the original work is properly cited.