title: MST1, a key player, in enhancing fast skeletal muscle atrophy.
abstract: BACKGROUND
  Skeletal muscle undergoes rapid atrophy upon denervation and the underlying mechanisms are complicated. FOXO3a has been implicated as a major mediator of muscle atrophy, but how its subcellular location and activity is controlled during the pathogenesis of muscle atrophy remains largely unknown. MST1 (Mammalian Sterile 20-like kinase 1) is identified as a central component of the Hippo signaling pathway. MST1 has been shown to mediate phosphorylation of FOXO3a at Ser207. Whether this MST1-FOXO signaling cascade exerts any functional consequence on cellular homeostasis remains to be investigated.
  
  
  RESULTS
  We identified that MST1 kinase was expressed widely in skeletal muscles and was dramatically up-regulated in fast- but not slow-dominant skeletal muscles immediately following denervation. The results of our histological and biochemical studies demonstrated that deletion of MST1 significantly attenuated denervation-induced skeletal muscle wasting and decreased expression of Atrogin-1 and LC3 genes in fast-dominant skeletal muscles from three- to five-month-old adult mice. Further studies indicated that MST1, but not MST2, remarkably increased FOXO3a phosphorylation level at Ser207 and promoted its nuclear translocation in atrophic fast-dominant muscles.
  
  
  CONCLUSIONS
  We have established that MST1 kinase plays an important role in regulating denervation-induced skeletal muscle atrophy. During the early stage of muscle atrophy, the up-regulated MST1 kinase promoted progression of neurogenic atrophy in fast-dominant skeletal muscles through activation of FOXO3a transcription factors.
authors: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Datun Road 15, Beijing 100101, China.
authors: Bin
authors: B
authors: Wei
authors: Wen
authors: W
authors: Dui
authors: Dong
authors: D
authors: Liu
authors: Yan
authors: Y
authors: Xing
authors: Zengqiang
authors: Z
authors: Yuan
authors: Guangju
authors: G
authors: Ji
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000378:metabolism; D051379:Mice; D009124:Muscle Proteins / Q000235:genetics; D018482:Muscle, Skeletal / Q000201:enzymology / Q000503:physiopathology*; D009133:Muscular Atrophy / Q000201:enzymology / Q000503:physiopathology*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism / Q000502:physiology*; D044843:SKP Cullin F-Box Protein Ligases / Q000235:genetics; D015398:Signal Transduction; D014158:Transcription, Genetic; D015854:Up-Regulation; D000099317:Hippo Kinases
chemical_list: D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D009124:Muscle Proteins; D017346:Protein Serine-Threonine Kinases; D044843:SKP Cullin F-Box Protein Ligases; C474033:FoxO3 protein, mouse; C486691:Fbxo32 protein, mouse; C490660:Stk4 protein, mouse; D000099317:Hippo Kinases
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