UBE2L3, a Partner of MuRF1/TRIM63, Is Involved in the Degradation of Myofibrillar Actin and Myosin - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Cells Année : 2021

UBE2L3, a Partner of MuRF1/TRIM63, Is Involved in the Degradation of Myofibrillar Actin and Myosin

Dulce Peris-Moreno
  • Fonction : Auteur
  • PersonId : 1207568
Mélodie Malige
  • Fonction : Collaborateur
Agnès Claustre
  • Fonction : Collaborateur
Andrea Armani
  • Fonction : Collaborateur
  • PersonId : 1274905
Christiane Deval
  • Fonction : Collaborateur
  • PersonId : 1274906
Daniel Béchet
Pierre Fafournoux
Marco Sandri
  • Fonction : Collaborateur
  • PersonId : 1274907
Lydie Combaret
Daniel Taillandier
Cécile Polge

Résumé

The ubiquitin proteasome system (UPS) is the main player of skeletal muscle wasting, a common characteristic of many diseases (cancer, etc.) that negatively impacts treatment and life prognosis. Within the UPS, the E3 ligase MuRF1/TRIM63 targets for degradation several myofibrillar proteins, including the main contractile proteins alpha-actin and myosin heavy chain (MHC). We previously identified five E2 ubiquitin-conjugating enzymes interacting with MuRF1, including UBE2L3/UbcH7, that exhibited a high affinity for MuRF1 (KD = 50 nM). Here, we report a main effect of UBE2L3 on alpha-actin and MHC degradation in catabolic C2C12 myotubes. Consistently UBE2L3 knockdown in Tibialis anterior induced hypertrophy in dexamethasone (Dex)-treated mice, whereas overexpression worsened the muscle atrophy of Dex-treated mice. Using combined interactomic approaches, we also characterized the interactions between MuRF1 and its substrates alpha-actin and MHC and found that MuRF1 preferentially binds to filamentous F-actin (KD = 46.7 nM) over monomeric G-actin (KD = 450 nM). By contrast with actin that did not alter MuRF1–UBE2L3 affinity, binding of MHC to MuRF1 (KD = 8 nM) impeded UBE2L3 binding, suggesting that differential interactions prevail with MuRF1 depending on both the substrate and the E2. Our data suggest that UBE2L3 regulates contractile proteins levels and skeletal muscle atrophy.
Fichier principal
Vignette du fichier
cells-10-01974-v2 on line version.pdf (12.19 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

hal-04183808 , version 1 (21-08-2023)

Identifiants

Citer

Dulce Peris-Moreno, Mélodie Malige, Agnès Claustre, Andrea Armani, Cécile Coudy-Gandilhon, et al.. UBE2L3, a Partner of MuRF1/TRIM63, Is Involved in the Degradation of Myofibrillar Actin and Myosin. Cells, 2021, 10 (8), pp.1974. ⟨10.3390/cells10081974⟩. ⟨hal-04183808⟩
11 Consultations
3 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More