title: Dose-dependent regulation of target gene expression and cell proliferation by c-Myc levels.
abstract: The proto-oncogene c-myc encodes a basic helix-loop-helix leucine zipper transcription factor (c-Myc). c-Myc plays a crucial role in cell growth and proliferation. Here, we examined how expression of c-Myc target genes and cell proliferation depend on variation of c-Myc protein levels. We show that proliferation rates, the number of cells in S-phase, and cell size increased in a dose-dependent manner in response to increasing c-Myc levels. Likewise, the mRNA levels of c-Myc responsive genes steadily increased with rising c-Myc levels. Strikingly, steady-state mRNA levels of c-Myc target genes did not saturate even at highest c-Myc concentrations. These characteristics predestine c-Myc levels as a cellular rheostat for the control and fine-tuning of cell proliferation and growth rates.
authors.affiliation: Department of Molecular Epigenetics; Helmholtz Center Munich; Center of Integrated Protein Science (CIPSM); Munich, Germany.
authors.forename: Marino
authors.initials: M
authors.lastname: Schuhmacher
authors.forename: Dirk
authors.initials: D
authors.lastname: Eick
mesh_terms: D002460:Cell Line; D049109:Cell Proliferation; D048429:Cell Size / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D059807:S Phase Cell Cycle Checkpoints / Q000187:drug effects; D013752:Tetracycline / Q000494:pharmacology
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D013752:Tetracycline
keywords: gene activity; titration; transactivation; transcription factor