Nurr1 enhances transcription of the human dopamine transporter gene through a novel mechanism

  title={Nurr1 enhances transcription of the human dopamine transporter gene through a novel mechanism},
  author={Paola Sacchetti and Todd R. Mitchell and James G. Granneman and Michael J. Bannon},
  journal={Journal of Neurochemistry},
The importance of the nuclear receptor nurr1 for the appropriate development of mesencephalic dopamine‐synthesizing neurons has been clearly demonstrated through the targeted disruption of the nurr1 gene. The persistence of nurr1 expression in adult tissue suggests a possible role for this transcription factor in the maintenance, as well as development, of the dopaminergic phenotype. To address this issue, we analyzed the effects of nurr1 on the transcriptional expression of the human dopamine… 

The Transcription Factor NURR1 Exerts Concentration-Dependent Effects on Target Genes Mediating Distinct Biological Processes

A large number of NURR1-responsive genes are identified and the potential importance of concentration-dependent NUR1 effects in the differential regulation of distinct NURR 1 target genes and biological pathways are demonstrated.

Dopamine neurons express multiple isoforms of the nuclear receptor nurr1 with diminished transcriptional activity

It is demonstrated that multiple splice variants of nurr1 are produced in rat and human dopamine neurons, which could represent a novel regulatory mechanism of nURr1 transcriptional activity and therefore, dopaminergic phenotype.

Direct Regulation of Pitx3 Expression by Nurr1 in Culture and in Developing Mouse Midbrain

It is shown that Nurr1 overexpression up-regulates that of Pitx3 in a dose-dependent manner by binding to a non-canonical NBRE consensus sequence, located at the 5′ site of the gene.

Covalent Modification and Regulation of the Nuclear Receptor Nurr1 by a Dopamine Metabolite

Nurr1, an orphan nuclear receptor with essential functions in developing dopamine cells

Nurr1 is a transcription factor that is expressed in the embryonic ventral midbrain and is critical for the development of dopamine neurons and plays additional less-well-elucidated roles in other regions of the central nervous system and in peripheral tissues.

Bdnf gene is a downstream target of Nurr1 transcription factor in rat midbrain neurons in vitro

It is demonstrated that following depolarization the hyperexpression of Nurr1 and the brain derived neurotrophic factor (BDNF) are phospholipase C and protein kinase C‐dependent and it is suggested that Nurr 1 might also influence the development and the function of midbrain dopaminergic neurons via direct regulation of Bdnf expression.

Orphan nuclear receptor Nurr1 directly transactivates the promoter activity of the tyrosine hydroxylase gene in a cell‐specific manner

It is shown that Nurr1, an orphan nuclear receptor critical for dopaminergic neuron development, directly transactivates the promoter activity of the TH gene in a cell type‐dependent manner, while it does not regulate the DBH promoter.

Requirements for Heterodimerization between the Orphan Nuclear Receptor Nurr1 and Retinoid X Receptors*

It is shown that nurr1 acts as a gene activator independently of RXR and through an AF2-independent mechanism, and heterodimerization with RXR is isotype-specific, involves multiple domains in the C-terminal region of nurR1, and requires RXR binding to DNA.



Nurr1, an orphan nuclear receptor, is a transcriptional activator of endogenous tyrosine hydroxylase in neural progenitor cells derived from the adult brain.

It is found that the influences of Nurr1 can be temporally and mechanistically uncoupled from the patterning influences of sonic hedgehog and FGF-8 or the more generic process of neuronal differentiation itself, suggesting that the midbrain dopaminergic identity is dictated by a combination of pan-dopaminergic and region-specific mechanisms.

A Response Element for the Homeodomain Transcription Factor Ptx3 in the Tyrosine Hydroxylase Gene Promoter

It is demonstrated that the homeodomain protein Ptx3 has the potential to act on the promoter of the TH gene in a markedly cell type‐dependent fashion and contributes to the regulation of TH expression in mesencephalic dopaminergic neurons.

Identification of a new brain-specific transcription factor, NURR1.

The identified and cloned a novel member of the nuclear receptor superfamily, which 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.

An isoform of Nurr1 functions as a negative inhibitor of the NGFI-B family signaling.

Neuroendocrine regulation of the hypothalamic pituitary adrenal axis by the nurr1/nur77 subfamily of nuclear receptors.

Examination of the role of the nurr1/nur77 subfamily of nuclear receptor transcription factors in the regulation of the hypothalamic/pituitary/adrenal axis at the neuroendocrine level shows that this nuclear receptor subfamily can regulate the expression of the CRF and POMC genes by interacting with a specific cis-acting sequence in their proximal promoter regions.

Differential regulation of transcription by the NURR1/NUR77 subfamily of nuclear transcription factors.

Comparative analysis of the transcription regulatory properties of NURR1 and NUR77 indicates that the proteins can display opposing transregulatory activities that are influenced by the specific cis-acting sequences to which they bind.

Heterodimerization between Members of the Nur Subfamily of Orphan Nuclear Receptors as a Novel Mechanism for Gene Activation

The data indicate that members of the Nur77 subfamily are most potent as heterodimers and that different dimers exhibit target sequence preference, and it is proposed that a combinatorial code relying on specific NurRE sequences might be responsible for the activation of subsets of target genes by one of the members of this subfamily of transcription factors.

Dopamine Biosynthesis Is Selectively Abolished in Substantia Nigra/Ventral Tegmental Area but Not in Hypothalamic Neurons in Mice with Targeted Disruption of the Nurr1 Gene

Dopamine was absent in the substantia nigra and ventral tegmental area of Nurr1-null mice, consistent with absent tyrosine hydroxylase (TH), L-aromatic amino acid decarboxylase, and other DA neuron markers, providing evidence for a new mechanism of DA depletion in vivo and suggesting a unique role for Nurr 1 in fetal development and/or postnatal survival.