Nuclear Receptors

Nuclear receptors are ligand activated transcription factors that control numerous biological functions. Consequently, altering activity of these receptors is proposed, and indeed documented, to affect many physiological and pathological conditions in experimental animals and humans. Thus, nuclear receptors have become a major target in the effort to treat numerous diseases. This book will shed light on and emphasize intricate processes involved in designing as well as discovering physiological and pharmacological modulators of these important proteins. World-renowned scientists will share with the reader their professional expertise and extensive experience acquired through decades working with nuclear receptors. Chapters address the various means and consequences of modulating nuclear receptor activity will be presented and discussed. These modulators cover a wide span of moieties ranging from synthetic chemicals to natural products. In addition, the classification of these chemicals ranges from pan agonists to selective agonists and inverse agonists to antagonists. They also include proteolytic means to obliterate the receptor in the event that modulating its activity through canonical pharmacological agents becomes less effective and/or less desirable due to anticipated or experienced toxicities. Modulation of receptor activity may also take place in the absence of a ligand or through manipulating the structure of the receptor itself by controlling posttranslational events.

The FactsBook Series has established itself as the best source of easily accessible and accurate facts about protein groups. They use an easy-to-follow format and are researched and compiled by experts in the field. This Factsbook is devoted to nuclear receptors. The first section presents an introduction and describes the mode of action of the receptors in general. The second section of the book contains detailed entries covering each type of receptor. Entries provide information on: Nomenclature and structure, Isolation, DNA binding properties, Ligands, Expression, Target genes, Knockouts, Disease association, Gene structure, promoter and isoforms, Chromosomal location, Amino acid sequences, Key references

Nuclear Receptors focuses on the structural analysis of nuclear receptors from the initial work using isolated protein domains to the more recent exciting developments investigating the conformational shape of full-length receptor complexes. The book also reviews the structure of key nuclear receptor co-regulatory proteins. It brings together, for the first time, a comprehensive review of nuclear receptor structure and the importance of receptor conformation underpinning allosteric regulation by different ligands (hormone, drugs, DNA response elements, protein-protein interactions) and receptor activity. The nuclear receptor superfamily, including receptors for steroid hormones and non-steroid ligands, are pivotal to normal physiology, regulating processes as diverse as reproduction, metabolism, the immune system and brain development. The first members of the family were cloned over 25 years ago, which heralded in the idea of a superfamily of intracellular receptor proteins that bound small molecule ligands: classical steroid hormones, vitamins, fatty acids and other products of metabolism. These signals are then transmitted through multiprotein receptor-DNA complexes, leading to the regulation of target genes, often in a cell-selective manner. The cloning of the receptor cDNAs also ushered in an era of unparalleled analysis of the mechanisms of action of these ligand-activated transcription factors. ​

In 1890 a case of myxedema was treated in Lisbon by the implantation of a sheep thyroid gland with the immediate improvement in the patient’s condition. A few years later, medications for the then ill-explained condition of the menopause included tablets made from cow ovaries. In the first quarter of the 20th century the identification of vitamin D, and its sunlight driven production in skin, paved the way to the elimination of rickets as a major medical problem. Twenty years or so later, Sir Vincent Wigglesworth established the endocrine basis of developmental moulting in insects, arguably the most commonly performed animal behaviour on Planet Earth. A paradigm that would unify these disparate observations arose between 1985 and 1987 beginning with the identification of the glucocorticoid receptor and the nuclear receptor super-family. What follows is a timely and positive manifestation of the capacity, productivity and value of international human scientific endeavour. Based on intrigue, lively competition and cooperation a global effort has rapidly fostered a school of biology with widespread ramifications for the understanding of metazoan animals, the human condition and the state of the planet. This book is the first this century to try and capture the spirit of this endeavour, to depict where the field is now and to identify some of the challenges and opportunities for the future.

The steroid / nuclear receptor superfamily is a large and growing group of transcription factors that are studied by a large and varied number of basic and clinical researchers. The first two chapters describe the evolutionary biology of the superfamily and explain how to clone and characterize new receptors. Chapter 3 shows how to identify the ligands of novel receptors and chapter 4 explains the kinetic analysis of receptor interactions. In chapter 5, the reader is guided through the functional characterization of coactivators using microinjection. The next section covers receptor phosphorylation, ligand regulated transcription, and hormone resistance syndromes. Chapter 9 describes the in vitro assembly of Hsp90 complexes and chapter 10 explains yeast as a model system for looking at receptor function. The final chapter shows how heterologous proteins can be regulated by fusion to the hormone binding domain of a receptor. Nuclear Receptors: A Practical Approach is a comprehensive guide to studying members of the superfamily and will be invaluable to all researchers old and new.

Nuclear Receptors are inducible transcription factors that mediate complex effects on development, differentiation and homeostasis. They regulate the transcription of their target genes through binding to DNA sequences. *Analysis of Nuclear Receptor Ligands*Structure/Function Analysis of Nuclear Receptors*Analysis of Nuclear Receptor Co-Factors and Chromatin Remodeling

This volume presents valuable techniques for studying the class of ligand-activated transcription factors known as nuclear receptors. After a brief overview of the history of the field, chapters cover methods to detect the receptors and their mRNAs in various tissues, protocols to characterize nuclear receptor modulators and activities, their signaling and roles in certain pathogenesis, molecular modeling of nuclear receptor-ligand interactions, as well as the utility of informatics in the field of nuclear receptors. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Nuclear Receptors: Methods and Experimental Protocols seeks to aid researchers working toward furthering our understanding of these vital receptors and their role in numerous pathological conditions.