Identification of a new brain-specific transcription factor, NURR1

Abstract

We have identified and cloned a novel member of the nuclear receptor superfamily. The cDNA was isolated from a mouse brain cDNA library and encodes a protein 598 amino acids in length with a predicted mol wt of 66 kilodaltons. The amino acid sequence of the protein is closely related to an additional family member and immediate early gene product, Nur77, and the novel factor is referred to as Nurr1 (Nur-related factor 1). The relationship between Nurr1 and Nur77 suggests that these proteins constitute an additional subfamily within the nuclear receptor superfamily. Like Nur77, the expression of Nurr1 is induced by membrane depolarization of PC12 cells. However, while Nur77 shows an early transcriptional response to nerve growth factor stimulation, the failure of Nurr1 to respond to this agent suggests a differential selectivity of the two proteins in terms of their transcriptional responses to specific stimuli. Finally, both proteins are differentially expressed during development and in tissues of the adult mouse. Unlike Nur77, Nurr1 appears to be predominantly located in brain tissue, suggesting a primary role for this putative transcription factor in regulation of gene expression in the central nervous system.

Activation of Nuclear Orphan Receptor NURR1 Transcription by NF-κB and Cyclic Adenosine 5′-Monophosphate Response Element-Binding Protein in Rheumatoid Arthritis Synovial Tissue

“…Orphan receptors, which comprise the second group, have all the structural features of steroid receptors; however, by definition, the corresponding ligands and functions of these receptors are not known (14). NURR1 is an orphan member of this superfamily that is expressed constitutively in the developing and adult CNS (15). The protein exhibits a close structural relationship to the orphan receptors NUR77 and NOR-1 (16,17).…”

Orphan nuclear receptors in drug discovery

“…The NR4A subfamily of nuclear receptors comprises three members, Nurr1, Nur77, and Nor1 [36][37][38]. They largely function as immediate-early genes, the expression and activation of which is regulated in a cell-type specific manner in response to a range of signals, such as mitogenic and apoptotic stimuli [39].…”

Probing conformational changes in orphan nuclear receptor: The NGFI-B intermediate is a partially unfolded dimer

“…In heterodimers, agonist-bound RXR contributes to transcriptional activation [11,12]. Members of this orphan receptors subgroup exhibit homologous DNA-binding domains, partially homologous ligand (like)-binding and transactivation domains [4].…”

“…Monomeric, homodimeric, or heterodimeric NR4A receptors regulate target gene transcription from target sequences such as AAAGGTCA, termed NGFI-B response elements [9,10] in a cell type-and promoterdependent manner [8,[11][12][13]. In addition, NGFI-B and Nurr1 act on DR5 elements…”