Negative autoregulation of c-myc transcription.
The introduction of activated c-myc and v-myc genes into a variety of non-established and established cells results in the suppression of endogenous c-myc expression. As measured in Rat-1 fibroblasts, the suppression occurs at the level of transcriptional initiation. Moreover, the extent of the down-regulation is proportional to the cellular concentration of c-myc protein, and the critical concentration range in which the endogenous c-myc RNA is effectively suppressed corresponds to that found in non-transformed cells. In addition, the autoregulatory mechanism is not only dependent on c-myc protein, but also requires additional trans-acting factors. These results support a role for c-myc in the regulation of cellular gene transcription and suggest that a negative feedback mechanism can act as a homeostatic regulator of c-myc expression in vivo.
Penn
L J
LJ
Growth Control and Development Laboratory, Imperial Cancer Research Fund, London, UK.
Brooks
M W
MW
Laufer
E M
EM
Land
H
H
D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005246:Feedback; D005786:Gene Expression Regulation; D006706:Homeostasis; D015151:Immunoblotting; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc; D011519:Proto-Oncogenes; D051381:Rats; D015183:Restriction Mapping; D012190:Retroviridae / Q000235:genetics; D012260:Ribonucleases; D013489:Suppression, Genetic; D014158:Transcription, Genetic; D014162:Transfection
D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D011505:Protein-Tyrosine Kinases; D012260:Ribonucleases