title: Identification of essential sequences for cellular localization in the muscle-specific ubiquitin E3 ligase MAFbx/Atrogin 1.
abstract: In skeletal muscle atrophy, upregulation and nuclear accumulation of the Ubiquitin E3 ligase MAFbx is essential for accelerated muscle protein loss, but the nuclear/cytoplasmic shuttling of MAFbx is undefined. Here we found that MAFbx contains two functional nuclear localization signals (NLS). Mutation or deletion of only one NLS induced cytoplasmic localization of MAFbx. We identified a non-classical NES located in the leucine charged domain (LCD) of MAFbx, which is leptomycin B insensitive. We demonstrated that mutation (L169Q) in LLXXL motif of LCD suppressed cytoplasmic retention of MAFbx. Nucleocytoplasmic shuttling of MAFbx represents a novel mechanism for targeting its substrates and its cytosolic partners in muscle atrophy.
authors.affiliation: Laboratoire de Génomique Fonctionnelle et Myogenèse, UMR 866 DMEM, INRA UM II, Montpellier, France.
authors.forename: Lagirand-Cantaloube
authors.initials: LC
authors.lastname: Julie
authors.forename: Batonnet-Pichon
authors.initials: BP
authors.lastname: Sabrina
authors.forename: Leibovitch
authors.initials: L
authors.lastname: Marie-Pierre
authors.forename: Serge A
authors.initials: SA
authors.lastname: Leibovitch
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D017124:Conserved Sequence; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D009133:Muscular Atrophy / Q000235:genetics / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D019913:Nuclear Localization Signals / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D044843:SKP Cullin F-Box Protein Ligases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid
chemical_list: D005231:Fatty Acids, Unsaturated; D009124:Muscle Proteins; D019913:Nuclear Localization Signals; C440907:FBXO32 protein, human; D044843:SKP Cullin F-Box Protein Ligases; C038753:leptomycin B