RAPID INHIBITION OF MYOGENIN-DRIVEN ACETYLCHOLINE-RECEPTOR SUBUNIT GENE-TRANSCRIPTION

In investigating the coupling of depolarization and transcription in s keletal muscle we have focused on how protein kinase C suppresses acet ylcholine receptor subunit genes. The activity of acetylcholine recept or subunit promoters in non-muscle cells co-transfected with myogenic factors and E proteins was measured, and their response to protein kin ase C activation analyzed. To simplify interpretation of results, gene activities rather than levels of reporter enzymes were assayed, trans criptional effects of phorbol esters were determined, with drug exposu res brief enough to preclude kinase depletion, and analysis was carrie d out with HeLa cells, which are not liable to myogenic conversion. My ogenin, which had been postulated previously to play a role in denerva tion supersensitivity (Neville et al., Mol. Cell. Neurobiol., 12, 511- 527, 1992), was found to be the only myogenic factor whose inactivatio n kinetics can account for the plasma membrane-protein kinase C-recept or gene cascade observed in intact muscle (Huang et al., Neuron, 9, 67 1-678, 1992).