21 research outputs found
G9a mediates Sharp-1–dependent inhibition of skeletal muscle differentiation
10.1091/mbc.E12-04-0311Molecular Biology of the Cell23244778-478
G9a mediates Sharp-1–dependent inhibition of skeletal muscle differentiation
10.1091/mbc.E12-04-0311Molecular Biology of the Cell23244778-478
Lysine methyltransferase G9a methylates the transcription factor MyoD and regulates skeletal muscle differentiation
10.1073/pnas.1111628109Proceedings of the National Academy of Sciences1093841-84
Preclinical testing of the glycogen synthase kinase-3β inhibitor tideglusib for rhabdomyosarcoma
Rhabdomyosarcoma (RMS) is the most common childhood soft tissue sarcoma. RMS often arise from myogenic precursors and displays a poorly differentiated skeletal muscle phenotype most closely resembling regenerating muscle. GSK3β is a ubiquitously expressed serine-threonine kinase capable of repressing the terminal myogenic differentiation program in cardiac and skeletal muscle. Recent unbiased chemical screening efforts have prioritized GSK3β inhibitors as inducers of myodifferentiation in RMS, suggesting efficacy as single agents in suppressing growth and promoting self-renewal in zebrafish transgenic embryonal RMS (eRMS) models in vivo. In this study, we tested the irreversible GSK3β-inhibitor, tideglusib for in vivo efficacy in patient-derived xenograft models of both alveolar rhabdomyosarcoma (aRMS) and eRMS. Tideglusib had effective on-target pharmacodynamic efficacy, but as a single agent had no effect on tumor progression or myodifferentiation. These results suggest that as monotherapy, GSK3β inhibitors may not be a viable treatment for aRMS or eRMS
G9a promotes proliferation and inhibits cell cycle exit during myogenic differentiation
10.1093/nar/gkw483Nucleic Acids Research44178129-814
Aurora kinase A-mediated phosphorylation of mPOU at a specific site drives skeletal muscle differentiation
10.1093/jb/mvz088JOURNAL OF BIOCHEMISTRY1672195-20