Volume 12 Supplement 1

17th International Conference on Human Retroviruses: HTLV and Related Viruses

Open Access

SQSTM1/p62 regulates HTLV-1 tax mediated NF-κB activation

Retrovirology201512(Suppl 1):O38

https://doi.org/10.1186/1742-4690-12-S1-O38

Published: 28 August 2015

HTLV-1-mediated cellular transformation relies on Tax-dependent activation of the NF-κB pathway, which has previously been shown to require Tax poly-ubiquitination and interaction with cellular factors, such as Optineurin (OPTN). The recent identification of OPTN as a selective autophagy receptor sharing high sequence similarities with sequestosome-1 (SQSTM-1/p62), a well-described selective autophagy receptor and NF-κB signaling adaptor, led us to hypothesize that Tax could hijack selective autophagy receptors for an efficient NF-κB activation. Using immunoprecipitation and confocal imaging of endogenous SQSTM/p62 in Tax-expressing cells or in HTLV-1 chronically infected T-cell lines, we showed that Tax interacts with SQSTM-1/p62. This interaction was independent of Tax ubiquitination and of the presence of the Tax PDZ-binding motif. Tax-mediated activation of NF-κB in p62-deficient cells was significantly reduced compared to wild type cells, indicating that SQSTM/p62 is necessary for Tax activity. Surprisingly however, over-expression of SQSTM-1/p62 or induction of autophagy led to a dramatic decrease in the amount of soluble Tax, along with a reduced induction of NF-κB. This suggests that Tax could be a substrate of selective autophagy. Altogether, our results reveal the double-edged consequences of Tax / SQSTM/p62 interaction, with the potentiation of Tax activity and the induction of Tax sequestration. They highlight the complex relationships that this viral protein has.

Authors’ Affiliations

(1)
Équipe Oncogenèse Rétrovirale
(2)
Équipe Labellisée (Ligue Nationale Contre le Cancer)
(3)
Centre International de Recherche en Infectiologie, INSERM U1111-CNRS UMR5308
(4)
École Normale Supérieure de Lyon
(5)
Université Lyon 1, LabEx ECOFECT -Eco-evolutionary dynamics of infectious diseases

Copyright

© Schwob et al. 2015

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), 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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