In the UPS family, which E2 enzymes collaborate with the E3 ligase MuRF1, a major actor of muscle atrophy? - Inria - Institut national de recherche en sciences et technologies du numérique Accéder directement au contenu
Poster Année : 2019

In the UPS family, which E2 enzymes collaborate with the E3 ligase MuRF1, a major actor of muscle atrophy?

Résumé

Muscle wasting is associated with many diseases and also physiological conditions (disuse, aging). Skeletal muscle mass is largely controlled by the ubiquitin-proteasome system (UPS) and thus by the ubiquitinating enzymes (E2s and E3s) that target substrates for subsequent degradation. MuRF1 is the only E3 known to target contractile proteins (α-actin, myosins) during catabolic situations. MuRF1 knock-out partially protected skeletal muscles from atrophy in denervated or immobilized animals. MuRF1 is therefore a putative target for preventing muscle wasting. However, MuRF1 depends on E2 ubiquitin conjugating enzymes for ubiquitin chain formation on the substrates. In this work, we demonstrated that only highly sensitive and complementary interactomic approaches (Surface Plasmon Resonance, Yeast three-Hybrid and split-GFP) allowed the identification of MuRF1 E2 partners. Among the 14 E2 expressed in muscle, 5 physically and functionally interacted with MuRF1. We also showed that telethonin, a MuRF1 substrate, governed the affinity between MuRF1 and two of these E2s. We are currently studying 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 mechanisms involved in the atrophying muscle program and for proposing new therapeutic approaches.
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Dates et versions

hal-02396255 , version 1 (05-12-2019)

Identifiants

  • HAL Id : hal-02396255 , version 1
  • PRODINRA : 489596

Citer

Cécile Polge, Stéphanie Cabantous, Agnes Claustre, Christiane Deval, Lydie Combaret, et al.. In the UPS family, which E2 enzymes collaborate with the E3 ligase MuRF1, a major actor of muscle atrophy?. EMBO Workshop - Proteostasis: From organelles to organisms, Nov 2019, Ericeira, Portugal. , 2019. ⟨hal-02396255⟩
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