Signal transduction for activation of cell cycle inducing factors during dedifferentiation of muscle cells

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The mouse skeletal muscle cell line C2SVT has been established by transfecting the C2 cells with the SV40 large T antigen gene under the control of an inducible promoter. When the large T is induced in preformed C2SVT myotubes, the terminally differentiated quiescent cells reenter the cell cycle to undergo mitosis. During this dedifferentiation process, only c-Jun among various nuclear protooncogene products was coordinately induced with the expression of large T.The transcription factor AP-1 was also activated. The experiments with antisense olignucleotides showed that the induced c-Jun, possibly as a homodimer, is essential for the myotubes to resume the cell cycle. When large T was induced in both the myoblasts and myotubes, neither the amount of phosphotyrosine, the activity of phospholipase C,Ras, nor MAP kinase was elevated. Thus, large T,a nuclear protein, is likely to induce the cell cycle without activating these cytoplasmic signaling molecules. Further, bacterially expressed GST-MyoD and GST-myogenin were shown to bind to large T expressed in the Sf-9 cells through the baculovirus system. Under examination are domains involved in this interaction and whether or not the growth supperssion function of thses MyoD family proteins is prevented by the interaction.