Switching Genes on and off: The Example of Nuclear Receptors
Nuclear receptors are a special class of transcription factors, which have the unique property to be specifically activated by small lipophilic ligands in the size of cholesterol (approx. 400 Da). Some of these ligands are known as important endocrine hormones, such as estradiol and testosterone, while others are metabolites of dietary compounds, such as fatty acids and cholesterol. Both types of molecules are of large physiological impact in health and disease and made nuclear receptors especially attractive for basic and applied research, such as in pharmaceutical industry.
Nuclear receptors form the largest family of transcription factors in metazoans (48 members in humans) and also belong to the best-understood regulatory proteins. Therefore, many principles of eukaryotic gene regulation, such as the interaction with co-activators and co-repressors, were first understood at the example of nuclear receptors.
In this Chapter, we will discuss principles of nuclear receptor signaling and the subdivision of the nuclear receptor superfamily into three sub-classes. Then we will have a look on the different molecular interactions of nuclear receptors. Furthermore, the physiological actions of nuclear receptors as sensors for various micro- and macronutrients are discussed. In addition, the structure of important members of the nuclear receptor superfamily and their natural and synthetic ligands are presented. Finally, the transactivating and repressing activities of nuclear receptors are explained through their interaction with co-factors.