Sublytic terminal complement attack induces c-fos transcriptional activation in myotubes.
Sublytic C5b-9 alters the molecular phenotype of myotubes by inhibiting muscle-specific gene expression. Here, we showed that C5b-9 induced c-fos mRNA and transcription. Using c-fos promoter-CAT constructs and electrophoretic mobility shift assay (EMSA), the minimal c-fos promoter activity was shown to increase within 30-min exposure to serum C5b-9, which also induced the binding of serum response factor (SRF), along with ternary complex factor (TCF) Elk1 and Sap1a to the serum response element. C5b-9 activated ERK1, which in turn activated Elk1 in myotubes. We propose that c-fos gene transcription associated with myotube dedifferentiation is induced by C5b-9 through ERK1-mediated assembly of serum response factor-ternary complex.
D000328:Adult; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D015938:Complement Membrane Attack Complex / Q000502:physiology*; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004789:Enzyme Activation / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology*; D016762:Genes, fos / Q000276:immunology*; D006801:Humans; D051821:Lymphoid Enhancer-Binding Factor 1; D051379:Mice; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D020218:Response Elements / Q000276:immunology; D026362:Serum Response Factor / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation / Q000276:immunology*; D050807:ets-Domain Protein Elk-1
D015938:Complement Membrane Attack Complex; D004268:DNA-Binding Proteins; C494112:ELK1 protein, human; C494113:Elk1 protein, mouse; D051821:Lymphoid Enhancer-Binding Factor 1; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D026362:Serum Response Factor; D014157:Transcription Factors; D050807:ets-Domain Protein Elk-1; D004247:DNA; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases