Three related brain nuclear receptors, NGFI-B, Nurr1, and NOR-1, as transcriptional activators

Abstract

Three related orphan nuclear receptors that are expressed in the brain, NGFI-B, Nurr1, and NOR-1, were studied to compare their function as transcriptional activators. NGFI-B was able to activate (in the absence of added hormone) in CV1 cells both an NGFI-B-responsive luciferase reporter gene (containing eight copies of a response element for NGFI-B upstream of a basal prolactin promoter driving the luciferase gene, NBRE(8)-LUC), a similar thyroid hormone-receptor-responsive reporter gene (TRE(3)-LUC), and a reporter gene with an authentic promoter from a Xenopus vitellogenin gene containing two binding sites for the estrogen receptor (vit-LUC). NGFI-B activated NBRE(8)-LUC and TRE(3)-LUC (but not the vitLUC) with an amino-terminal activation domain. Nurr1 was less promiscuous as a transcriptional activator, activating.the NBRE(8)-LUC better than NGFI-B, but less than NGFI-B at the other reporter genes. NOR-1 activated only the NBRE(8)-LUC reporter gene. These results indicate that closely related nuclear receptors may differentiate between response elements or promoters and that different activation mechanisms exist depending on the promoter. This may contribute to regulation of specificity of target gene expression in the brain.

The Transcription Factor NGFI-B (Nur77) and Retinoids Play a Critical Role in Acute Neuroleptic-Induced Extrapyramidal Effect and Striatal Neuropeptide Gene Expression

“…Thus, it appears that unlike in the immune system, NGFI-B and Nor-1 expressed in the striatum have distinct functions. It has been shown that Nor-1, unlike NGFI-B (Nur77) and Nurr1, cannot form heterodimers with members of the RXR family (Paulsen et al, 1995;Zetterström et al, 1996). This reinforces the possibility of an involvement of an NGFI-B/ RXR complex in the effects investiged here.…”

“…On the contrary, the effects of haloperidol on the expression of DYN (Figure 4a, b), c-fos (Figure 4c, d), and Nor-1 (Figure 4e, f), a close homologue of NGFI-B (Paulsen et al, 1995), are similar in WT and NGFI-B (À/À) mice. However, the effect of haloperidol on Nor-1 mRNA levels is significantly higher in NGFI-B-deficient mice compared to WT mice (Figure 4f).…”

Nur77 Gene Knockout Alters Dopamine Neuron Biochemical Activity and Dopamine Turnover

“…This observation suggests the possibility that Nur77 may alter Nurr1-dependent transcriptional activity in DA cells. The molecular and structural organization of Nur77 is very close to Nurr1, and it has been reported that both can interact with the same responsive elements (Maira et al 1999;Paulsen et al 1995;Perlmann and Jansson 1995). Thus, we might expect that induction of Nur77 would enhance Nur-dependent transcriptional activity in DA cells.…”

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

“…In humans, the NR4A subfamily of orphan nuclear receptors (NRs) comprises three members: NGFI-B (NR4A1), also referred as NAK1, Nur77, ST-59, TR3 and eight others aliases [8]; NURR1 (NR4A2), and NOR1 (NR4A3). 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].…”

“…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…”