Inducible Gene Expression, Volume 1

Cells have evolved multiple strategies to adapt the composition and quality of their protein equipment to needs imposed by changes in intra- and extracellular conditions. The appearance of pro teins transmit- ting novel functional properties to cells can be controlled at a transcrip- tional, posttranscriptional, translational or posttranslational level. Extensive research over the past 15 years has shown that transcriptional regulation is used as the predominant strategy to control the production of new proteins in response to extracellular stimuli. At the level of gene transcription, the initiation ofmRNA synthesis is used most frequently to govern gene expression. The key elements controlling transcription initiation in eukaryotes are activator proteins (transactivators) that bind in a sequence-specific manner to short DNA sequences in the of genes. The activator binding sites are elements of larger proximity control units, ca lied promoters and enhancers, which bind many distinct proteins. These may synergize or negatively cooperate with the activators. The do novo binding of an activator to DNA or, if already bound to DNA, its functional activation is what ultimately turns on a high-level expression of genes. The activity of transactivators is controlled by signalling pathways and, in some cases, transactivators actively partici- pate in signal transduction by moving from the cytoplasm into the nuc1eus. In this first volume of Inducible Gene Expression, leading scientists in the field review six eukaryotic transactivators that allow cells to respond to various extracellular stimuli by the expression of new proteins.