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This gene encodes a member of the steroid-thyroid hormone-retinoid receptor superfamily. Expression is induced by phytohemagglutinin in human lymphocytes and by serum stimulation of arrested fibroblasts. The encoded protein acts as a nuclear transcription factor. Translocation of the protein from the nucleus to mitochondria induces apoptosis. Three transcript variants encoding two distinct isoforms have been identified for this gene. Chenodeoxycholic acid derivative-induced apoptosis of SNU-1 gastric cancer cell lines is mediated by mitochondria and by Nur77. Ectopic expression of TR3 in both H460 and Calu-6 lung cancer cell lines promoted their cell cycle progression and BrdU incorporation. Expression of Nurr1 and NGFI-B plays an important role in human adrenal cortex and its neoplasms, including possible regulation of steroidogenesis. Hepatitis B virus X protein induced transcription. In transgenic mice expressing human TR3 orphan receptor, as described in this review, TR3 inhibits formation of smooth muscle cell-rich atherosclerotic lesions. Induction of apoptosis by TPA and VP-16 is through induction of TR3 expression and translocation from nucleus to cytosol, which may be a novel signal pathway for TR, and a new biological function to exert its effect on apoptosis in gastric cancer cells. NGFI-B-dependent transcription of proopiomelanocortin gene is antogonized by glucocorticoid receptor. NGFIB plays a crucial role in adrenal zonation by regulating 3beta-hydroxysteriod dehydrogenase 2 gene transcription. NR4A nuclear receptors NR4A1, NR4A2, NR4A3 are potential transcriptional mediators of inflammatory signals in activated macrophages. NUR77 binds to BCL-2 and effects its role and phenotype. Nur77 activated by HIF under hypoxic conditions regulates production of the peptide hormone precursor POMC. Nur77 activation and its apoptotic activity are regulated by small heterodimer partner protein. Nur77 drives transcription of PAI-1 through direct binding to an NGFI-B responsive element (NBRE), indicating monomeric binding and a ligand-independent mechanism. Nur77, itself, is transcriptionally up-regulated by TNFalpha. Nur77 has a role in the stabilization of HIF-1alpha and in tumor progression and metastasis. Nur77 is an important regulator of HSD3B2 promoter activity. Nur77, which is regulated by a MAPK pathway activated via arrestin 2, modulates NK(1)R-mediated nonapoptotic programmed cell death. P. 743:""Nothern blot analysis of Nur77 mRNA expression revealed that PGF(2alpha) and Butaprost, but not Bimatoprost, induced upregulation of Nur77 mRNA expression in human trabecular meshwork cells. Promyelocytic leukemia protein PML inhibits Nur77-mediated transcription through specific functional interactions. RXRalpha is responsible for TR3 nucleocytoplasmic translocation. TR3 has a distinct role and functional mode in mediating tretinoin-induced signalling. TR3 is a modulator of vascular endothelial cell proliferation and arrests endothelial cells in the G1 phase of the cell cycle by influencing cell cycle protein levels. TR3 orphan nuclear receptor mediates apoptosis through up-regulating E2F1 in human prostate cancer cells. TR3/Nur77 translocation from the nucleus may initiate the apoptotic cascade in colon cancer cells by stimulating other cytosolic proapoptotic molecules to associate with mitochondria. The genes identified here are novel candidates as key early mediators of VEGF-induced endothelial functions. The repressive effect of Nur77 on IL-2 promoter activation is mediated through inhibition of the transcription factor complex nuclear factor-kappaB. We review here recent studies on the glucocorticoid receptor and the orphan receptors Nur77 and RORgamma. Ligand-dependent activation of Nur77 through nuclear pathways induces cell death. Nongenotropic function of RXRalpha and its involvement in the regulation of the Nur77-dependent apoptotic pathway. Plays a dual role in selective regulation of apoptosis and cell cycle in gastric cancer cells. Upregulation by Wnt-1.
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