IDENTIFICATION OF A NEW BRAIN-SPECIFIC TRANSCRIPTION FACTOR, NURR1

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.