In the UPS family, which E2 enzymes collaborate with the E3 ligase MuRF1, a major actor ofmuscle atrophy?
| Autor: | Polge, Cécile, Cabantous, Stéphanie, Claustre, Agnes, Deval, Christiane, Combaret, Lydie, Attaix, Didier, Taillandier, Daniel |
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| Přispěvatelé: | Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: | |
| Zdroj: | EMBO Workshop-Proteostasis: From organelles to organisms EMBO Workshop-Proteostasis: From organelles to organisms, Nov 2019, Ericeira, Portugal. 2019 EMBO Workshop-Proteostasis: From organelles to organisms, Nov 2019, Ericeira, Portugal., 2019 |
| Popis: | Muscle wasting is associated with many diseases and also physiological conditions (disuse, aging). Skeletalmuscle mass is largely controlled by the ubiquitin-proteasome system (UPS) and thus by the ubiquitinatingenzymes (E2s and E3s) that target substrates for subsequent degradation. MuRF1 is the only E3 known to targetcontractile proteins (α-actin, myosins) during catabolic situations. MuRF1 knock-out partially protected skeletalmuscles from atrophy in denervated or immobilized animals. MuRF1 is therefore a putative target for preventingmuscle wasting. However, MuRF1 depends on E2 ubiquitin conjugating enzymes for ubiquitin chain formation onthe substrates.In this work, we demonstrated that only highly sensitive and complementary interactomic approaches (SurfacePlasmon Resonance, Yeast three-Hybrid and split-GFP) allowed the identification of MuRF1 E2 partners. Amongthe 14 E2 expressed in muscle, 5 physically and functionally interacted with MuRF1. We also showed thattelethonin, a MuRF1 substrate, governed the affinity between MuRF1 and two of these E2s. We are currentlystudying the capacity of E2-MuRF1 duos to target the main contractile proteins both in vitro and in vivo.We report here the first MuRF1-E2s network, which may prove valuable for deciphering the precise mechanismsinvolved in the atrophying muscle program and for proposing new therapeutic approaches. |
| Databáze: | OpenAIRE |
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