c-myc gene is transcribed at high rate in G0-arrested fibroblasts and is post-transcriptionally regulated in response to growth factors.
There is increasing evidence that at least some of the cellular homologues to retroviral oncogenes (c-onc or proto-oncogenes) are directly linked to the control of cell growth (for a review see ref. 1). Among these, c-myc, the cellular homologue to the avian myelocytomatosis virus (MC29) oncogene, has been shown to express high levels of mRNA during early G0/G1 phase after mitogenic stimulation of T lymphocytes by concanavalin A or of fibroblasts by platelet-derived growth factor (PDGF) or serum. An attractive model proposed for this regulation is that the c-myc gene is strongly repressed in cells arrested in the G0 phase of the cell cycle by a growth factor-sensitive repressor. We have investigated an alternative model of post-transcriptional regulation. This latter model leads to two testable predictions. First, that c-myc mRNA should be unusually unstable, which we have confirmed. And second, that there would be a high level of constitutive expression, a situation opposite to that implied by the repressor model. Here we report that c-myc gene is indeed transcribed at a high rate in G0-arrested chinese hamster lung fibroblasts, although the level of mature c-myc mRNA is barely detectable. The early and dramatic increase in c-myc mRNA levels when these resting cells are stimulated by growth factors is not accompanied by any appreciable change in the transcription rate of c-myc gene. Taken together these findings support a model of post-transcriptional regulation of c-myc expression at the level of mRNA degradation.
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D005347:Fibroblasts / Q000378:metabolism; D006133:Growth Substances / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology; D007399:Interphase; D009857:Oncogenes; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology; D014158:Transcription, Genetic
D006133:Growth Substances; D007328:Insulin; D012333:RNA, Messenger; D013917:Thrombin