title: Serine/Threonine Kinase 40 (Stk40) Functions as a Novel Regulator of Skeletal Muscle Differentiation.
abstract: Skeletal muscle differentiation is a precisely coordinated process, and the molecular mechanism regulating the process remains incompletely understood. Here we report the identification of serine/threonine kinase 40 (Stk40) as a novel positive regulator of skeletal myoblast differentiation in culture and fetal skeletal muscle formation in vivo We show that the expression level of Stk40 increases during skeletal muscle differentiation. Down-regulation and overexpression of Stk40 significantly decreases and increases myogenic differentiation of C2C12 myoblasts, respectively. In vivo, the number of myofibers and expression levels of myogenic markers are reduced in the fetal muscle of Stk40 knockout mice, indicating impaired fetal skeletal muscle formation. Mechanistically, Stk40 controls the protein level of histone deacetylase 5 (HDAC5) to maintain transcriptional activities of myocyte enhancer factor 2 (MEF2), a family of transcription factor important for skeletal myogenesis. Silencing of HDAC5 expression rescues the reduced myogenic gene expression caused by Stk40 deficiency. Together, our study reveals that Stk40 is required for fetal skeletal muscle development and provides molecular insights into the control of the HDAC5-MEF2 axis in skeletal myogenesis.
authors.affiliation: From the Laboratory of Molecular Developmental Biology, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai 200025, China.
authors.forename: Ke
authors.initials: K
authors.lastname: He
authors.affiliation: From the Laboratory of Molecular Developmental Biology, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai 200025, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Hu
authors.affiliation: From the Laboratory of Molecular Developmental Biology, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai 200025, China.
authors.forename: Hongyao
authors.initials: H
authors.lastname: Yu
authors.affiliation: From the Laboratory of Molecular Developmental Biology, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai 200025, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Wang
authors.affiliation: From the Laboratory of Molecular Developmental Biology, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai 200025, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Tang
authors.affiliation: From the Laboratory of Molecular Developmental Biology, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai 200025, China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Gu
authors.affiliation: From the Laboratory of Molecular Developmental Biology, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai 200025, China.
authors.forename: Laixiang
authors.initials: L
authors.lastname: Ge
authors.affiliation: the Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200032, China.
authors.forename: Hongye
authors.initials: H
authors.lastname: Wang
authors.affiliation: the Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200032, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Li
authors.affiliation: the Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200032, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Hu
authors.affiliation: From the Laboratory of Molecular Developmental Biology, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai 200025, China, yjin@sibs.ac.cn.|the Key Laboratory of Stem Cell Biology, Chinese Academy of Sciences Center for Excellence in Molecular Cell Science, Institute of Health Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China, and.
authors.forename: Ying
authors.initials: Y
authors.lastname: Jin
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D005333:Fetus / Q000166:cytology* / Q000378:metabolism; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D064326:MEF2 Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000166:cytology* / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D064326:MEF2 Transcription Factors; D017346:Protein Serine-Threonine Kinases; C547661:Stk40 protein, mouse; C498618:Hdac5 protein, mouse; D006655:Histone Deacetylases
keywords: HDAC5; MEF2; Stk40; cell differentiation; histone deacetylase (HDAC); myogenesis; serine/threonine protein kinase; skeletal muscle