title: The role and regulation of MAFbx/atrogin-1 and MuRF1 in skeletal muscle atrophy.
abstract: Skeletal muscle atrophy occurs in many chronic diseases and disuse conditions. Its severity reduces patient recovery, independence and quality of life. The discovery of two muscle-specific E3 ubiquitin ligases, MAFbx/atrogin-1 and Muscle RING Finger-1 (MuRF1), promoted an expectation of these molecules as targets for therapeutic development. While numerous studies have determined the conditions in which MAFbx/atrogin-1 and MuRF1 mRNA levels are regulated, few studies have investigated their functional role in skeletal muscle. Recently, studies identifying new target substrates for MAFbx/atrogin-1 and MuRF1, outside of their response to the initiation of muscle atrophy, suggest that there is more to these proteins than previously appreciated. This review will highlight our present knowledge of MAFbx/atrogin-1 and MuRF1 in skeletal muscle atrophy, the impact of potential therapeutics and their known regulators and substrates. Finally, we will comment on new approaches that may expand our knowledge of these two molecules in their control of skeletal muscle function.
authors.affiliation: Centre for Physical Activity and Nutrition Research, School of Exercise and Nutrition Sciences, Deakin University, 221 Burwood Highway, 3125, Burwood, Australia.
authors.forename: Victoria C
authors.initials: VC
authors.lastname: Foletta
authors.forename: Lloyd J
authors.initials: LJ
authors.lastname: White
authors.forename: Amy E
authors.initials: AE
authors.lastname: Larsen
authors.forename: Bertrand
authors.initials: B
authors.lastname: Léger
authors.forename: Aaron P
authors.initials: AP
authors.lastname: Russell
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000503:physiopathology; D000375:Aging / Q000502:physiology; D000818:Animals; D002100:Cachexia / Q000503:physiopathology; D003714:Denervation; D003920:Diabetes Mellitus / Q000503:physiopathology; D005215:Fasting / Q000502:physiology; D006801:Humans; D007103:Immobilization / Q000009:adverse effects; D009124:Muscle Proteins / Q000502:physiology*; D009133:Muscular Atrophy / Q000378:metabolism*; D029424:Pulmonary Disease, Chronic Obstructive / Q000503:physiopathology; D051437:Renal Insufficiency / Q000503:physiopathology; D044843:SKP Cullin F-Box Protein Ligases / Q000502:physiology*; D018805:Sepsis / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000503:physiopathology; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000502:physiology*
chemical_list: D009124:Muscle Proteins; D000070584:Tripartite Motif Proteins; C486691:Fbxo32 protein, mouse; D044843:SKP Cullin F-Box Protein Ligases; C440908:TRIM63 protein, human; D044767:Ubiquitin-Protein Ligases