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Rôle des récepteurs de l'autophagie sélective dans la modulation de la signalisation NF- κB par l'oncoprotéine Tax du virus HTLV-1

Aurélien Schwob 1
1 Oncogenèse rétrovirale – Retroviral Oncogenesis
CIRI - Centre International de Recherche en Infectiologie - UMR
Abstract : NF-κB constitutive activation is a key step in the HTLV-1-mediated T lymphocytes transformation process. This activation is mainly driven by the viral protein Tax, which recruits the IKKγ regulator factor. Previous work performed in our lab showed that Tax-induced NF-κB activation is promoted by the interaction with several cellular factors such as Optineurin (OPTN) and Tax1-binding protein 1 (TAX1BP1), two members of the Sequestosome-Like Receptors (SLR) family, rising the hypothesis of functional interplay vetween NFκB signaling and the autophagic pathway.Our study demonstrates that Tax interacts with the p62 receptor, which is another SLR member, in a direct, ubiquitin independent manner. Tax and p62 form complexes located at autophagic membranes, together with IKKγ. P62 potentiates the Tax-mediated NF-κB activation. Unexpectedly, p62 over-expression inhibits Tax-mediated NF-κB activation by inducing Tax cytoplasmic depletion. These results show that p62 plays a dual role on Tax in a dose-dependent manner. Preliminary data suggest that Tax is also able to interact with other SLR, with various consequences on activation of the NF-κB pathway.This work contributes to the further caracterization of the complex interplay between Tax, NF-κB signaling and the autophagic pathway, suggesting the use of autophagic membranes as viral signaling platforms.
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https://tel.archives-ouvertes.fr/tel-01865808
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Submitted on : Sunday, September 2, 2018 - 1:04:46 AM
Last modification on : Thursday, December 26, 2019 - 10:37:24 PM
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  • HAL Id : tel-01865808, version 1

Citation

Aurélien Schwob. Rôle des récepteurs de l'autophagie sélective dans la modulation de la signalisation NF- κB par l'oncoprotéine Tax du virus HTLV-1. Virologie. Université de Lyon, 2017. Français. ⟨NNT : 2017LYSEN027⟩. ⟨tel-01865808⟩

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