SQSTM-1/p62 potentiates HTLV-1 Tax-mediated NF-κB activation through its ubiquitin binding function
| العنوان: | SQSTM-1/p62 potentiates HTLV-1 Tax-mediated NF-κB activation through its ubiquitin binding function |
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| المؤلفون: | Aurélien, Schwob, Elodie, Teruel, Louise, Dubuisson, Florence, Lormières, Pauline, Verlhac, Yakubu Princely, Abudu, Janelle, Gauthier, Marie, Naoumenko, Fanny-Meï, Cloarec-Ung, Mathias, Faure, Terje, Johansen, Hélène, Dutartre, Renaud, Mahieux, Chloé, Journo |
| المساهمون: | Oncogenèse rétrovirale – Retroviral Oncogenesis (OR), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Autophagie infection et immunité - Autophagy Infection Immunity (APY), Immunité infection vaccination (I2V), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR128-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, The Arctic University of Norway, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), The Arctic University of Norway [Tromsø, Norway] (UiT) |
| المصدر: | Scientific Reports, Vol 9, Iss 1, Pp 1-17 (2019) Scientific Reports Scientific Reports, Nature Publishing Group, 2019, 9 (1), ⟨10.1038/s41598-019-52408-x⟩ Scientific Reports, 2019, 9 (1), ⟨10.1038/s41598-019-52408-x⟩ |
| بيانات النشر: | Nature Research, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Ubiquitylation, Recombinant Fusion Proteins, lcsh:Medicine, Article, Cell Line, Jurkat Cells, Mice, Sequestosome-1 Protein, Animals, Humans, Leukaemia, Tumour virus infections, RNA, Small Interfering, lcsh:Science, ComputingMilieux_MISCELLANEOUS, Human T-lymphotropic virus 1, Ubiquitin, lcsh:R, NF-kappa B, [SDV.BBM.MN]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, VDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710, Gene Products, tax, HTLV, VDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710, HEK293 Cells, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, RNA Interference, lcsh:Q, Protein Binding, Signal Transduction, Cell signalling |
| الوصف: | The NF-κB pathway is constitutively activated in adult T cell leukemia, an aggressive malignancy caused by Human T Leukemia Virus type 1 (HTLV-1). The viral oncoprotein Tax triggers this constitutive activation by interacting with the ubiquitin-rich IKK complex. We previously demonstrated that Optineurin and TAX1BP1, two members of the ubiquitin-binding, Sequestosome-1 (SQSTM-1/p62)-like selective autophagy receptor family, are involved in Tax-mediated NF-κB signaling. Here, using a proximity-dependent biotinylation approach (BioID), we identify p62 as a new candidate partner of Tax and confirm the interaction in infected T cells. We then demonstrate that p62 knock-out in MEF cells as well as p62 knock-down in HEK293T cells significantly reduces Tax-mediated NF-κB activity. We further show that although p62 knock-down does not alter NF-κB activation in Jurkat T cells nor in infected T cells, p62 does potentiate Tax-mediated NF-κB activity upon over-expression in Jurkat T cells. We next show that p62 associates with the Tax/IKK signalosome in cells, and identify the 170–206 domain of p62 as sufficient for the direct, ubiquitin-independent interaction with Tax. However, we observe that this domain is dispensable for modulating Tax activity in cells, and functional analysis of p62 mutants indicates that p62 could potentiate Tax activity in cells by facilitating the association of ubiquitin chains with the Tax/IKK signalosome. Altogether, our results identify p62 as a new ubiquitin-dependent modulator of Tax activity on NF-κB, further highlighting the importance of ubiquitin in the signaling activity of the viral Tax oncoprotein. |
| اللغة: | English |
| تدمد: | 2045-2322 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=pmid_dedup__::4c5b0d1df61cdde70b59819b1b71ba91Test https://hdl.handle.net/10037/17534Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.pmid.dedup....4c5b0d1df61cdde70b59819b1b71ba91 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20452322 |
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