The NR4A orphan nuclear receptors: mediators in metabolism and diseases

The NR4A subfamily is orphan nuclear receptors that belong to the larger nuclear receptors (NRs) superfamily of eukaryotic transcription factors. The NR4A subfamily includes three members, namely Nur77 (NR4A1), Nurr1 (NR4A2) and Nor1 (NR4A3) which are gene regulators and participate in diverse biological functions. Though the ligands for these receptors are presently unidentified, they are thought to be constitutively active. NR4A acts as molecular switches in gene regulation and their action is increasingly seen to be modulated by complex network of cellular signaling pathways. Members of the NR4A are expressed in tissue-specific fashion which indicates their selective control of various biological processes. Data reveal a host of functions governed by the NR4A subfamily members including general metabolism, immunity, cellular stress, memory, insulin sensitivity and cardiac homeostasis by regulating specific target genes whose products participates in such processes. Moreover, these receptors have a role in the onset and progression of various diseases such as various types of cancer, inflammation, atherosclerosis and obesity. In this review, a concise overview of the current understanding of the important metabolic roles governed by NR4A members including their participation in a number of diseases shall be provided.