NUCLEAR RECEPTORS 2000

Keystone Symposia, Silverthorne CO

Investigators

Abstract

DESCRIPTION (taken from the application) The fields of molecular endocrinology and signal transduction have undergone explosive expansion over the last few years. The cloning of nuclear receptors and key modulators of their activity has brought intense excitement to the quest to understand the cellular regulation of gene expression. Pathways for steroid hormone action, cell-cycle control, co-activator and co-repressor proteins, oncogenic activation, tumor suppression, and medical therapeutics have all been dramatically elucidated within the last several years. Substantial and striking advances have been made in structural biology and crystallization of receptor DNA binding domains, ligand binding domains, both in the presence and absence of hormones. The molecular basis for antagonist action is now being worked out and the physiologic role of receptors is being dissected through targeted mutagenesis of the vertebrate genome. Recent efforts to unravel the mechanisms of initiation of transcription have revealed amazing complexity, much of it based on discoveries with nuclear receptors. We now have a much better appreciation of the complexities and a rudimentary understanding of the signaling mechanisms of early development. These same pathways play a continuing role throughout early postnatal development and adult life. The intracellular nuclear receptors represent a large superfamily of structurally related transcription factors, now over 50 in number in vertebrate genomes which include the steroid receptors, thyroid hormone receptors, and receptors for certain vitamins such as Vitamin D3 and retinoids. The "orphan receptors" termed as such because their ligands are currently unknown, as are many of their target genes, constitute the largest sub-group within the family and now number more than 40. In summary, this is a time of great activity of both fundamental and medical significance. It is the goal of this meeting to capture this intensity, crystallize it and send people back to their laboratories and companies with an advanced understanding of a rapidly moving field.