Structure and Function of the Nur77 Receptor Subfamily, a Unique Class of Hormone Nuclear Receptors

J.   B.   Eells; J.      Witta; J.   B.   Otridge; E.      Zuffova; V.   M.   Nikodem

Abstract

Although structurally related to other steroid thyroid hormone nuclear receptors, Nur77, Nurr1 and NOR-1 represent a distinct subfamily of nuclear receptors, the Nur77 receptor subfamily. In addition to very strong structural homologies among these three nuclear receptors, all can be rapidly induced as immediate early genes. Furthermore, they have similar DNA binding and transactivation properties, and can function in the absence of a not yet known ligand(s). The present review addresses the properties of the Nur77 receptor subfamily, including gene structure, promotor elements, regulation of expression, DNA binding and transactivation properties, and potential physiological and developmental roles. The functions of all three receptors in negative selection of T-cells, the regulation of the hypothalamus-pituitary-adrenal axis and the potential functional redundancy are discussed. Also reviewed is the role of Nurr1 in the differentiation and function of midbrain dopaminergic neurons, as demonstra ted by the ablation of Nurr1 function in mice, and the potential implications for Nurr1 in Parkinsons disease and or schizophrenia. Although similar in many structural and functional aspects, subtle differences in certain properties, regulation and expression patterns of the different receptors may result in different physiological roles of these proteins, while similarities may account for a redundancy of function. Much has been described about the regulation of these proteins, however, future research will need to focus on the identification of potential ligands and the target genes that are regulated by this unique class of transcription factors.

Keywords: Nur77 Receptor, Hormone Nuclear Receptors, Nurr1, Parkinsons disease, Schizophrenia, protein, Promoter Structure, In Vitro DNA Binding, Transactivation