title: The E3 SUMO ligase Nse2 regulates sumoylation and nuclear-to-cytoplasmic translocation of skNAC-Smyd1 in myogenesis.
abstract: Skeletal and heart muscle-specific variant of the α subunit of nascent polypeptide associated complex (skNAC; encoded by NACA) is exclusively found in striated muscle cells. Its function, however, is largely unknown. Previous reports have demonstrated that skNAC binds to m-Bop/Smyd1, a multi-functional protein that regulates myogenesis both through the control of transcription and the modulation of sarcomerogenesis, and that both proteins undergo nuclear-to-cytoplasmic translocation at the later stages of myogenic differentiation. Here, we show that skNAC binds to the E3 SUMO ligase mammalian Mms21/Nse2 and that knockdown of Nse2 expression inhibits specific aspects of myogenic differentiation, accompanied by a partial blockade of the nuclear-to-cytoplasmic translocation of the skNAC-Smyd1 complex, retention of the complex in promyelocytic leukemia (PML)-like nuclear bodies and disturbed sarcomerogenesis. In addition, we show that the skNAC interaction partner Smyd1 contains a putative sumoylation motif and is sumoylated in muscle cells, with depletion of Mms21/Nse2 leading to reduced concentrations of sumoylated Smyd1. Taken together, our data suggest that the function, specifically the balance between the nuclear and cytosolic roles, of the skNAC-Smyd1 complex might be regulated by sumoylation.
authors.affiliation: Charité - University Medicine Berlin, Institute of Physiology, Charitéplatz 1, D-10117 Berlin, Germany.
authors.forename: Janine
authors.initials: J
authors.lastname: Berkholz
authors.affiliation: Charité - University Medicine Berlin, Institute of Physiology, Charitéplatz 1, D-10117 Berlin, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Michalick
authors.affiliation: University Hospital Tubingen, Medical Clinic, Department of Sports Medicine, Hoppe-Seyler-Strasse 6, D-72076 Tubingen, Germany barbara.munz@med.uni-tuebingen.de.
authors.forename: Barbara
authors.initials: B
authors.lastname: Munz
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D051379:Mice; D018832:Molecular Chaperones / Q000235:genetics* / Q000378:metabolism*; D009024:Morphogenesis / Q000235:genetics*; D024510:Muscle Development / Q000235:genetics*; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D058207:Sumoylation / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D018832:Molecular Chaperones; D009124:Muscle Proteins; C096485:Smyd1 protein, mouse; D014157:Transcription Factors; C096099:nascent-polypeptide-associated complex; D044767:Ubiquitin-Protein Ligases
keywords: Mms21; Myogenic differentiation; Nse2; Smyd1; Sumoylation; m-Bop; skNAC