title: MURF2B, a novel LC3-binding protein, participates with MURF2A in the switch between autophagy and ubiquitin proteasome system during differentiation of C2C12 muscle cells.
abstract: The ubiquitin proteasome system and macroautophagy are proteolytic pathways essential in the maintenance of cellular homeostasis during differentiation and remodelling of skeletal muscle. In both pathways, proteins to be degraded are tagged with polyubiquitin. In skeletal muscles, the MURF2 proteins display E3 ubiquitin ligase structure suggesting that they may covalently attach ubiquitin polypeptides to still unknown target proteins. So far only MURF2A isoforms were studied and shown to interact with p62/SQSTM1, a protein implicated in macroautophagic and ubiquitin proteasome system degradations. Here, we analyzed the MURF2B and MURF2A proteins and show that the ratio of the isoforms changes during differentiation of muscle C2C12 cells and that the shift of the isoforms expression follows the sequential activation of autophagic or proteasomal degradation. We also show that MURF2B has a functional domain needed for its interaction with LC3, a protein needed for autophagic vesicles formation. Using specific MURF2 RNAi cells we observed that MURF2A and MURF2B are both needed for the formation of autophagosomes and that in the absence of MURF2B, the cells expressing MURF2A display an activated ubiquitin proteasome system implicated in the degradation of p62/SQSTM1 by UPS. Altogether, our results indicate that MURF2A and MURF2B proteins could participate in the molecular switch between the two ubiquitin degradative pathways.
authors.affiliation: University Paris Diderot, Sorbonne Paris Cité, Unité de Biologie Fonctionnelle et Adaptative, CNRS EAC4413, Paris, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Pizon
authors.forename: Sofia
authors.initials: S
authors.lastname: Rybina
authors.forename: Fabien
authors.initials: F
authors.lastname: Gerbal
authors.forename: Florence
authors.initials: F
authors.lastname: Delort
authors.forename: Patrick
authors.initials: P
authors.lastname: Vicart
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Baldacci
authors.forename: Eric
authors.initials: E
authors.lastname: Karsenti
mesh_terms: D000818:Animals; D001343:Autophagy / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D051379:Mice; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D010588:Phagosomes / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D025801:Ubiquitin / Q000378:metabolism*
chemical_list: D009124:Muscle Proteins; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex