Rapid inhibition of myogenin-driven acetylcholine receptor subunit gene transcription.
In investigating the coupling of depolarization and transcription in skeletal muscle we have focused on how protein kinase C suppresses acetylcholine receptor subunit genes. The activity of acetylcholine receptor subunit promoters in non-muscle cells co-transfected with myogenic factors and E proteins was measured, and their response to protein kinase C activation analyzed. To simplify interpretation of results, gene activities rather than levels of reporter enzymes were assayed, transcriptional effects of phorbol esters were determined, with drug exposures brief enough to preclude kinase depletion, and analysis was carried out with HeLa cells, which are not liable to myogenic conversion. Myogenin, which had been postulated previously to play a role in denervation supersensitivity (Neville et al., Mol. Cell. Neurobiol., 12, 511-527, 1992), was found to be the only myogenic factor whose inactivation kinetics can account for the plasma membrane-protein kinase C-receptor gene cascade observed in intact muscle (Huang et al., Neuron, 9, 671-678, 1992).
Huang
C F
CF
Department of Biochemistry and Cell Biology, State University of New York at Stony Brook 11794.
Lee
Y S
YS
Schmidt
M M
MM
Schmidt
J
J
D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D009132:Muscles / Q000378:metabolism; D018008:Myogenin / Q000037:antagonists & inhibitors / Q000502:physiology*; D010703:Phorbol Esters / Q000494:pharmacology; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors; D011401:Promoter Regions, Genetic; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011950:Receptors, Cholinergic / Q000235:genetics*; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
C503799:MYOG protein, human; D018008:Myogenin; D010703:Phorbol Esters; D011950:Receptors, Cholinergic; D014157:Transcription Factors; D011493:Protein Kinase C; D010744:Phosphoric Monoester Hydrolases