ABSTRACT
One of the major alterations in eukaryotic cells upon exposure to different extracellular environments is a change in their gene expression profiles. In simple eukaryotes such as yeast, these changes might be in response to changes in the nutrients available. In more complex multicellular organisms, cells respond to different types of stimuli, generated from either contact with neighboring cells, short range signals involving secreted molecules or long range signals transported by the circulatory system such as hormones. In addition, cells respond to various stresses that might either be mechanical or be due to external agents such as UV light. Over recent years, our understanding of how extracellular signals are sensed and transmitted into nuclear responses has increased substantially. Numerous different pathways and different types of mechanisms for transmitting these signals have been elucidated. These signaling pathways play critical roles both in the adult and during development and in many cases, the components of these pathways function in multiple different processes. Furthermore, in many diseases, notably cancer, some of the key genetic lesions are in genes encoding components of these signaling pathways which results in the perturbation of signal transmission to the nucleus. Ultimately, the signaling pathways often converge either directly or indirectly, on transcription factor substrates. Indirect effects might be via coregulatory proteins known as coactivator and corepressor proteins. For the purposes of this review, we define transcription factors as the DNA binding components of complexes which up- or down-regulate transcription. Coregulatory proteins are the non-DNA binding components of these complexes. We use the term transcriptional regulator when these two classes of proteins are referred to together.
