Mechanisms regulating transient expression of mammalian cytokine genes and cellular oncogenes.

Publisher Summary This chapter describes the molecular mechanisms currently thought to be operating to control the level of accumulation of transiently expressed growth factor gene, and cellular oncogene products synthesized by mammalian cells stimulated to undergo proliferation. Such transient gene expression is the result of complex but coordinated biochemical regulatory pathways operating at many levels within the cell. These include precise regulation of transcription initiation, elongation, termination, control of post-transcriptional mRNA processing, and selective mRNA degradation, as well as numerous other translational and post-translational control mechanisms. In certain cases, it has been experimentally demonstrated, both in vitro and in vivo , that the association of specific protein factors with their cognate binding sites in the promoter and enhancer regions of genes determines whether the gene will be transcriptionally active. In this regard, one of the conceptually most gratifying discoveries to emerge recently has been the demonstration that, the protein products of certain previously identified nuclear oncogenes are themselves trans-activating transcriptional regulatory molecules. For example, the protein product of the transiently expressed c-jun oncogene, Jun, has been identified as a member of the AP-1 family of trans-activating proteins that bind specifically to the AP-1 promoter elements found adjacent to most phorbol-ester-induced genes.