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Poster De Conférence Année : 2022

MuRF1/TRIM63 & UBE2s: A Synergy in Muscle Atrophy

Résumé

Skeletal muscle mass is reduced during many diseases (cancer, sepsis, heart failure, kidney diseases, etc.) or physiological situations (disuse, aging), resulting in decreased strength, resistance to drug-treatments and increased mortality. The main cellular mechanism controlling muscle mass is the ubiquitin-proteasome system (UPS). Within the UPS, the E3 ligase MuRF1/TRIM63 targets for degradation several myofibrillar proteins, including the main contractile proteins: alpha-actin and myosin. However, MuRF1 depends on UBE2 ubiquitinconjugating enzymes (E2s) for ubiquitin chain formation on the substrates. A previous study identified five E2 enzymes (E2L3, E2E1, E2J1, E2J2 and E2G1) interacting with MuRF1[1], which represent enzyme couples potentially druggable for fighting against muscle atrophy. Here, we focused on E2L3 that exhibits high affinity towards MuRF1 (KD = ~50 nM) and E2E1, an E2 that depends on the presence of telethonin (a MuRF1 substrate), for efficient MuRF1 binding. References: [1] Polge et al. 2017. A muscle-specific MuRF1-E2 network requires stabilization of MuRF1-E2 complexes by telethonin, a newly identified substrate. JCSM. DOI: 10.1002/ jcsm.12249 [2] Polge et al. 2018. UBE2E1 is preferentially expressed in the cytoplasm of slow twitch fibers and protects skeletal muscles from exacerbated atrophy upon Dexamethasone treatment. Cells. DOI: 10.3390/cells7110214 [3] Peris-Moreno et al. 2021. UBE2L3, a Partner of MuRF1/TRIM63, Is Involved in the Degradation of Myofibrillar Actin and Myosin. Cells. doi: 10.3390/cells10081974. [4] Polge et al. 2011. Muscle actin is polyubiquitinylated in vitro and in vivo and targeted for breakdown by the E3 ligase MuRF1. FASEB J. doi: 10.1096/fj.11-180968.
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Dates et versions

hal-04176528 , version 1 (03-08-2023)

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  • HAL Id : hal-04176528 , version 1

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Dulce Peris-Moreno, Agnès Claustre, Mélodie Malige, Andrea Armani, Cécile Coudy-Gandilhon, et al.. MuRF1/TRIM63 & UBE2s: A Synergy in Muscle Atrophy. EMBO Workshop Ubiquitin and ubiquitin-like proteins in health and disease, Sep 2022, Cavtat, Croatia. . ⟨hal-04176528⟩
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