title: Reciprocal inhibition between MyoD and STAT3 in the regulation of growth and differentiation of myoblasts.
abstract: The development of myoblasts is regulated by various growth factors as well as by intrinsic muscle-specific transcriptional factors. In this study, we analyzed the roles for STAT3 in the growth and differentiation of myoblasts in terms of cell cycle regulation and interaction with MyoD using C2C12 cells. Here we found that STAT3 inhibited myogenic differentiation induced by low serum or MyoD as efficiently as the Ras/mitogen-activated protein kinase cascade. As for this mechanism, we found that STAT3 not only promoted cell cycle progression through the induction of c-myc but also inhibited MyoD activities through direct interaction. STAT3 inhibited not only DNA binding activities of MyoD but also its transcriptional activities. However, the inhibited transcriptional activities were restored by the supplement of p300/CBP and PCAF, suggesting that STAT3 might deprive MyoD of these transcriptional cofactors. In addition, we found that MyoD inhibited DNA binding activities of STAT3, thereby inhibiting STAT3-dependent cell growth and survival of Ba/F3 cells. These results suggest that the development of muscle cells is regulated by the coordination of cytokine signals and intrinsic transcription factors.
authors.affiliation: Department of Hematology/Oncology, Osaka University Graduate School of Medicine, 2-2, Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Kataoka
authors.forename: Itaru
authors.initials: I
authors.lastname: Matsumura
authors.forename: Sachiko
authors.initials: S
authors.lastname: Ezoe
authors.forename: Soichi
authors.initials: S
authors.lastname: Nakata
authors.forename: Eri
authors.initials: E
authors.lastname: Takigawa
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Sato
authors.forename: Akira
authors.initials: A
authors.lastname: Kawasaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Yokota
authors.forename: Koichi
authors.initials: K
authors.lastname: Nakajima
authors.forename: Armando
authors.initials: A
authors.lastname: Felsani
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Kanakura
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D050822:Cytokine Receptor gp130; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D004347:Drug Interactions; D050881:E1A-Associated p300 Protein; D015870:Gene Expression / Q000187:drug effects; D005982:Glutathione Transferase / Q000235:genetics; D008562:Membrane Glycoproteins / Q000235:genetics / Q000494:pharmacology; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000494:pharmacology; D017570:MyoD Protein / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D032446:Myoblasts / Q000166:cytology* / Q000187:drug effects; D018008:Myogenin / Q000494:pharmacology; D041681:NIH 3T3 Cells; D009687:Nuclear Proteins / Q000494:pharmacology; D010766:Phosphorylation; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000494:pharmacology; D019908:Proto-Oncogene Proteins c-raf / Q000494:pharmacology; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000235:genetics; D011993:Recombinant Fusion Proteins; D050796:STAT3 Transcription Factor; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation; D014162:Transfection
chemical_list: D015703:Antigens, CD; D004268:DNA-Binding Proteins; C052130:GAL4 protein, S cerevisiae; C494200:Il6st protein, mouse; D008562:Membrane Glycoproteins; D017570:MyoD Protein; C503801:Myog protein, mouse; D018008:Myogenin; D009687:Nuclear Proteins; D016271:Proto-Oncogene Proteins c-myc; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D011993:Recombinant Fusion Proteins; D050796:STAT3 Transcription Factor; D029701:Saccharomyces cerevisiae Proteins; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D050822:Cytokine Receptor gp130; D004247:DNA; D050881:E1A-Associated p300 Protein; C494361:Ep300 protein, mouse; D005982:Glutathione Transferase; D019908:Proto-Oncogene Proteins c-raf; D020928:Mitogen-Activated Protein Kinases