Organization of the human orphan nuclear receptor Nurr1 gene

Torii, Tashiyuki; Kawarai, Toshitaka; Nakamura, Shotaro; Kawakami, Hideshi

doi:10.1016/s0378-1119(99)00064-5

Cited by 42 publications

(28 citation statements)

References 25 publications

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“…2 Since no ligands have been identified to this group of receptors yet, they are referred to as nuclear orphan receptors. TR3/Nur77 and its closely related family members, Not-1 (also called Nurr1 and RNR-1) 3,4 and NOR-1 (also called MINOR and TEC), 5,6 constitute a distinct subfamily within the nuclear receptor superfamily. 5,[6][7][8] TR3 was shown to be an immediate early response gene whose expression was rapidly induced by a variety of growth stimuli, including various growth factors, phorbol ester and cAMP-dependent pathways.…”

Section: Introductionmentioning

confidence: 99%

Nuclear orphan receptor TR3/Nur77 mediates melanoma cell apoptosis

Yu¹,

Kumar²,

Fang³

et al. 2007

Cancer Biology & Therapy

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TR3 was originally recognized for its role in the regulation of cell survival and differentiation, however, it was recently found to be a potent pro-apoptotic protein. In order to characterize the role of TR3 in melanoma cell apoptosis, we studied expression of TR3 in melanoma cell lines and tissues, its subcellular distribution and function during apoptosis using various expression and RNA interference vectors. We found that TR3 was constitutively expressed in both cultured melanoma cells and melanoma tissues. TR3 expression was significantly decreased in advanced melanomas comparing to benign nevi. Over-expression of wild type TR3 or mutant TR3 lacking the DNA binding domain resulted in massive apoptosis in melanoma cells, whereas stable knockdown of TR3 using RNA interference resulted in melanoma cell resistance to apoptosis induced by chemotherapeutic agents ATRA and cisplatin. We further demonstrated that apoptosis in melanoma cells was mediated, at least partially, through TR3 mitochondrial translocation but not alteration in TR3 expression levels. Our results suggest that TR3 is an important apoptosis inducing factor in melanoma cells. Decreased expression of TR3 in metastatic melanoma cells may contribute to their reduced apoptotic potential and increased resistance to chemotherapy.

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Section: Introductionmentioning

confidence: 99%

Nuclear orphan receptor TR3/Nur77 mediates melanoma cell apoptosis

Yu¹,

Kumar²,

Fang³

et al. 2007

Cancer Biology & Therapy

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“…The genomic DNA of human NR4A2 gene (GenBank accession number AB019433) has been cloned and characterized recently by two research groups from Japan [Ichinose et al, 1999;Torii et al, 1999], which has facilitated the mutation identi®cation in this gene. The NR4A2 gene was mapped to chromosome 2q22±q23 [Mages et al, 1994]; it is approximately 8 kb long and contains eight exons.…”

Section: Introductionmentioning

confidence: 99%

“…The human NR4A2 gene encodes a protein with 598 amino acids and has nearly 99.5% similarity in protein sequence to murine Nurr1 gene [Law et al, 1992]. The protein-coding region of the NR4A2 gene starts from exon 3; both exons 1 and 2 are untranslated regions [Ichinose et al, 1999;Torii et al, 1999].…”

Section: Introductionmentioning

confidence: 99%

Mutation analysis of the human NR4A2 gene, an essential gene for midbrain dopaminergic neurogenesis, in schizophrenic patients

et al. 2001

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Recent studies have revealed that an orphan receptor gene of the steroid/thyroid hormone nuclear receptor superfamily, the Nurr1 gene, is essential for the neurogenesis and differentiation of dopaminergic neurons in the midbrain of mice. Transgenic mice lacking the Nurr1 gene soon die after birth and are devoid of dopaminergic neurons in the midbrain. Heterozygous mice survive postnatally without obvious locomotor deficits; however, they have increased vulnerability to dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In view of the importance of dopamine neurotransmission in brain function, we were interested to know if the human homologous gene of murine Nurr1, the NR4A2 gene, may play a role in the pathogenesis of schizophrenia. We systematically sequenced all the exons of the human NR4A2 gene to search for molecular variants in a cohort of Chinese schizophrenic patients from Taiwan. Two molecular variants were identified: a G-insertion in intron 6 (designated IVS6 + 17 [see text] + 18insG), and a G-deletion in the untranslated exon 1 (designated c.-469delG). The IVS6 + 17 [see text] + 18insG is a polymorphic one; further case control study, however, did not reveal association of this polymorphism with schizophrenia. The c.-469delG is a rare variant found in two unrelated patients among 177 schizophrenic patients, but not in 130 nonpsychotic controls. The result suggests that the c.-469delG and possibly other variants of the NR4A2 gene may be of relevance to the complex factors involved in the pathogenesis of schizophrenia.

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“…The Nurr1 gene is of interest because Nurr1 knockout mice have selective and complete agenesis of SN and ventral tegmental area DAergic neurons (Zetterstrom et al, 1997;Le et al, 1998;Saucedo-Cardenas et al, 1998). The human Nurr1 (NOT) gene has been mapped to chromosome 2p22-23 (Magest et al, 1994), and its sequence has recently been identified (Ichinose et al, 1999;Tori et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Reduced Nurrl Expression Increases the Vulnerability of Mesencephalic Dopamine Neurons to MPTP‐Induced Injury

Conneely

et al. 1999

Journal of Neurochemistry

155

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Mutation in the Nurr1 gene, a member of the nuclear receptor superfamily, causes selective agenesis of dopaminergic neurons in the midbrain of null mice. Homozygous Nurr1 knockout mice (Nurr1Ϫ/Ϫ) die 1 day after birth, but heterozygous mice (Nurr1ϩ/Ϫ) survive postnatally without obvious locomotor deficits. Although adult Nurr1ϩ/Ϫ mice show significantly reduced Nurr1 protein levels in the substantia nigra (SN), they display a normal range of tyrosine hydroxylase-positive neuron numbers in the SN and normal levels of dopamine in the striatum. The reduction in Nurr1 expression in Nurr1ϩ/Ϫ mice, however, confers increased vulnerability to the selective dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) compared with wild-type (Nurr1ϩ/ϩ) mice. This study suggests that Nurr1 may play an important role in maintaining mature mesencephalic dopaminergic neuron function and that a defect in Nurr1 may increase susceptibility to SN injury. Key Words: Nurr1-Knockout mice-Dopaminergic neurons-Mesencephalon-1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-Parkinson's disease.

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Organization of the human orphan nuclear receptor Nurr1 gene

Cited by 42 publications

References 25 publications

Nuclear orphan receptor TR3/Nur77 mediates melanoma cell apoptosis

Nuclear orphan receptor TR3/Nur77 mediates melanoma cell apoptosis

Mutation analysis of the human NR4A2 gene, an essential gene for midbrain dopaminergic neurogenesis, in schizophrenic patients

Reduced Nurrl Expression Increases the Vulnerability of Mesencephalic Dopamine Neurons to MPTP‐Induced Injury

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