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Low levels of HTLV-2 Tax conjugation to ubiquitin and SUMO do not impede Tax-mediated activation of NF-κB

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HAL Id: inserm-00924956

https://www.hal.inserm.fr/inserm-00924956

Submitted on 7 Jan 2014

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Low levels of HTLV-2 Tax conjugation to ubiquitin and

SUMO do not impede Tax-mediated activation of NF-κB

Chloé Journo, Amandine Bonnet, Arnaud Favre-Bonvin, Jocelyn Turpin,

Jennifer Vinera, Emilie Côté, Sébastien Chevalier, Youmna Kfoury, Ali

Bazarbachi, Claudine Pique, et al.

To cite this version:

Chloé Journo, Amandine Bonnet, Arnaud Favre-Bonvin, Jocelyn Turpin, Jennifer Vinera, et al.. Low

levels of HTLV-2 Tax conjugation to ubiquitin and SUMO do not impede Tax-mediated activation of

NF-κB. Retrovirology, BioMed Central, 2014, 11 (Suppl 1), pp.O42. �10.1186/1742-4690-11-S1-O42�.

�inserm-00924956�

(2)

O R A L P R E S E N T A T I O N

Open Access

Low levels of HTLV-2 Tax conjugation to ubiquitin

and SUMO do not impede Tax-mediated

activation of NF-B

Chloé Journo

1*

, Amandine Bonnet

2

, Arnaud Favre-Bonvin

2

, Jocelyn Turpin

1

, Jennifer Vinera

1

, Emilie Côté

1

,

Sébastien A Chevalier

1

, Youmna Kfoury

3

, Ali Bazarbachi

3

, Claudine Pique

2

, Renaud Mahieux

1

From

16th International Conference on Human Retroviruses: HTLV and Related Viruses

Montreal, Canada. 26-30 June 2013

Constitutive activation of NF-B by HTLV-1 Tax is a key event in the process of T lymphocyte immortaliza-tion and leukemogenesis. Tax1 is post-translaimmortaliza-tionally modified by both ubiquitin and SUMO. These modifica-tions were originally thought to be required for Tax1-mediated NF-B activation by allowing recruitment of IKK-g/NEMO together with Tax1 in Golgi-associated cytoplasmic domains, followed by activation of the IKK complex and RelA/p65 nuclear translocation. Although HTLV-2 Tax also activates the canonical NF-B path-way, the requirement of post-translational modifications had not been investigated so far. We therefore com-pared the ubiquitination, SUMOylation, and acetylation patterns of Tax2 and Tax1. We first show that in con-trast to Tax1, Tax2 conjugation to endogenous ubiquitin and SUMO is barely detectable while both Tax2 and Tax1 are acetylated. Consistent with these observations, overexpression of the E2 ubiquitin-conjugating enzyme Ubc13 does not affect Tax2 conjugation to ubiquitin and Tax2-mediated NF-B activation. We further iden-tify the domains surrounding Tax1 lysine residues K4-10 and K6-10 as critical determinants of Tax conju-gation to ubiquitin and SUMO, respectively. We finally demonstrate that a non-ubiquitinable, non-SUMOylable, and non-acetylable Tax2 mutant retains a significant ability to activate transcription from a NF-B-dependent promoter after partial activation of the IKK complex and induction of RelA/p65 nuclear translocation. Taken together, these results thus indicate that Tax2 does not share Tax1 requirements toward ubiquitination and

SUMOylation for efficient NF-B activation and high-light key distinctions between both viral proteins. These results will be discussed in the light of the recent find-ings from other labs.

Authors’ details

1Oncogenèse Rétrovirale, équipe labellisée Ligue nationale contre le cancer,

CIRI, INSERM U1111-CNRS UMR5308, Université Lyon 1, Ecole Normale Supérieure de Lyon, LabEx ECOFECT, Lyon, Cedex 07, France.2Institut

Cochin, INSERM U1016-CNRS UMR8104, Université Paris Descartes, Paris, France.3Department of Internal Medicine, Faculty of Medicine, American

University of Beirut, Beirut, Lebanon.

Published: 7 January 2014

doi:10.1186/1742-4690-11-S1-O42

Cite this article as:Journo et al.: Low levels of HTLV-2 Tax conjugation to ubiquitin and SUMO do not impede Tax-mediated activation of NF-B. Retrovirology 2014 11(Suppl 1):O42.

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1Oncogenèse Rétrovirale, équipe labellisée Ligue nationale contre le cancer,

CIRI, INSERM U1111-CNRS UMR5308, Université Lyon 1, Ecole Normale Supérieure de Lyon, LabEx ECOFECT, Lyon, Cedex 07, France Full list of author information is available at the end of the article Journo et al. Retrovirology 2014, 11(Suppl 1):O42

http://www.retrovirology.com/content/11/S1/O42

© 2014 Journo 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. The Creative Commons Public Domain Dedication waiver (http:// creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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