Bøger i Progress in Gene Expression serien

Intracellular Receptors: New Instruments for a Symphony of Signals In the late eighteenth century, it was proposed on theoretical grounds that each of the body's organs, beginning with the brain, must be "a factory and laboratory of a specific humor which it returns to the blood", and that these circulating signals "are indispensable for the life of the whole" (Bordeu 1775). During the nineteenth cen­ tury, some remarkable physiological experiments revealed the actions of humoral factors that affected the for and function of multiple tissues, organs and organ sys­ tems within the body (Berthold 1849); much later, the chemical and molecular na­ ture of some of those factors was determined. Against this deep historical backdrop of the founding studies of intercellular signaling, molecular biology sprang into existence a mere forty years ago, rooted in the revelation of regulable gene expression in bacteria. But contemporaneous with those classical analyses of transcriptional regulation of the lactose operon, the mod­ em era of signal transduction was inaugurated by the identification of cAMP as a second messenger --- an intracellular mediator of hormonal activation of glycogen catabolism (Sutherland and RaIl 1960). Later in that same decade, it emerged that cAMP is a critical signal not only in metazoans, but even in bacteria, where it serves an analogous function as a critical switch that activates expression of genes re­ quired for catabolism of complex carbon sources, including those of the lactose operon.

1. The Role of Heat Shock Proteins in the Regulation of Steroid Receptor Function.- 2. Subcellular and Subnuclear Trafficking of Steroid Receptors.- 3. Structure and Function of the Steroid and Nuclear Receptor Ligand-Binding Domain.- 4. Structure and Function of the Steroid and Nuclear Receptor DNA Binding Domain.- 5. Modulation of Steroid/Nuclear Receptor Dimerization and DNA Binding by Ligands.- 6. Molecular Mechanisms of Nuclear-Receptor-Mediated Transcriptional Activation and Basal Repression.- 7. Transcriptional Cross-Talk by Steroid Hormone Receptors.- 8. Chromatin and Steroid-Receptor-Mediated Transcription.- 9. Regulation of Glucocorticoid and Estrogen Receptor Activity by Phosphorylation.- 10. Monomeric Nuclear Receptors.- 11. Orphan Nuclear Receptors and Their Ligands.

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 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 first of two volumes which aim to cover all established eukaryotic transcription factor systems that are direct targets for the signal transduction pathways. Topics covered include: ISGF3 (the interferon response); NF-KB (the pathogenic response); and dorsal (the morphogenetic response).

Fortunately, however, research during the past seven years on the mechanisms that control gene expression in eukaryotes has been extremely successful in generating a wealth of information on the basic strategies of transcriptional control.

The intensive study of molecular events leading to cellular transformation in tissue culture or in intact organisms culminated in the identification of 100 or more genes that can be defined as oncogenes or tumor suppressor genes.

The intensive study of molecular events leading to cellular transformation in tissue culture or in intact organisms culminated in the identification of 100 or more genes that can be defined as oncogenes or tumor suppressor genes.