Disease relevance of NR2F2

• Attachment of the nuclear localization signal from the simian virus 40 large T antigen (Flu tag) to the amino terminus of ARP-1/COUP-TFII abolished its ability to bind to DNA without affecting its repressor activity [1].
• Our results strongly suggest that an active MAP kinase pathway is essential for COUP-TFII expression in human breast cancer cells [2].
• In contrast, combination of ARP-1 and HNF-4 transactivated different apoCII promoter segments as well as a minimal adenovirus major late promoter driven by the regulatory element CIIB [3].
• In the attached nonneoplastic adrenal cortex of the adenomas, immunoreactivity for COUP-TFII was markedly increased compared to that in nonpathological adrenal cortex in adults and was especially marked in the zona glomerulosa in the attached adrenal of aldosteroma (P < 0.001) and the zona fasciculata in that of Cushing's adenoma (P < 0.05) [4].
• Transient transfection assays showed that site A is necessary and sufficient for RXR alpha-mediated transactivation of the apoAI gene basal promoter in human hepatoma HepG2 cells in the presence of RA and that this transactivation is abolished by increasing amounts of cotransfected ARP-1 [5].

High impact information on NR2F2

• This protein, designated apoAI regulatory protein-1 (ARP-1), is a novel member of the steroid hormone receptor superfamily [6].
• ARP-1 also bound to a thyroid hormone-responsive element and to regulatory regions of the apoB, apoCIII, insulin, and ovalbumin genes [6].
• The involvement of ARP-1 in the regulation of apoAI gene expression suggests that it may participate in lipid metabolism and cholesterol homeostasis [6].
• ARP-1 bound to DNA as a dimer, and its dimerization domain was localized to the COOH-terminal region [6].
• Regulation of the apolipoprotein AI gene by ARP-1, a novel member of the steroid receptor superfamily [6].

Chemical compound and disease context of NR2F2

• EXPERIMENTAL DESIGN: PCDGF functions and signaling pathways in dexamethasone-induced apoptosis were studied using a representative dexamethasone-sensitive multiple myeloma cell line ARP-1 [7].

Biological context of NR2F2

• In thecal cells, immunoreactive COUP-TFII was consistently elevated throughout the menstrual cycle, whereas Ad4BP/SF-1 immunoreactivity increased according to the development of the follicle [8].
• A mutational analysis indicated that the binding site for COUP-TFII/ARP-1 in the ATPA regulatory element 1 is an imperfect direct repeat of a nuclear receptor response element (A/GGGTCA) with a spacer of three nucleotides [9].
• COUP-TFI and COUP-TFII regulate expression of the NHE through a nuclear hormone responsive element with enhancer activity [10].
• Transactivation is greater for COUP-TFII, is increased for either COUP isoform by the presence of high serum concentrations, and is greatly reduced by mutations preventing COUP binding [10].
• Importantly, reexpression of COUP-TFII in TAM-S cells to levels comparable to those in MCF-7 was shown to increase 4-OHT-mediated growth inhibition and increased apoptosis [11].

Anatomical context of NR2F2

• In the ovarian follicle and corpora lutea, immunoreactive DAX-1 protein was detected predominantly in granulosa cells, whereas COUP-TFII was identified in thecal cells [8].
• Antibodies against apolipoprotein regulatory protein (ARP-1) altered DNA-protein interactions in electrophoretic mobility shift assays using oligonucleotides representing either promoter site and rat liver or cultured cell nuclear extracts [12].
• Functional assays in HeLa cells showed that COUP-TFII/ARP-1 represses the ATPA promoter activity in a dose- and sequence-dependent manner [9].
• Activation of the MAP kinase pathway induces chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) expression in human breast cancer cell lines [2].
• In kidney, the glomerular endothelium and Bowman's capsule were immunopositive for COUP-TFII [13].

Associations of NR2F2 with chemical compounds

• COUP-TFII immunoreactivity in the gastro-intestinal tract, liver and spleen were detected in mesenchymal cells, sinusoid endothelium and reticuloendothelium, respectively [13].
• Expression of COUP-TFII induced by either retinoic acid or dimethyl sulfoxide in differentiating P19 cells increases NHE expression [10].
• However, transcriptional repression mediated by ARP1 acting through CTIP1 did not appear to involve recruitment of a trichostatin A-sensitive histone deacetylase(s) to the template, suggesting that this repression pathway may be distinct from that utilized by several other nuclear receptors [14].
• Disruption of arp1 resulted in reddish-pink conidia and increased C3 binding [15].
• The orphan receptors COUP-TFI and COUP-TFII play an important role in development and differentiation by activating specific genes and by modulating the activity of nuclear receptors including estrogen receptor alpha (ERalpha) and retinoic acid receptors (RARs) [16].

Physical interactions of NR2F2

• EMSA showed that the prepared His-tagged COUP-TFII could firmly bind to -201 to +35 fragment of hTERT promoter [17].

Regulatory relationships of NR2F2

• Recent studies have demonstrated that DAX-1 and COUP-TFII negatively regulate adrenal 4 binding protein (Ad4BP)/steroidogenic factor-1 (SF-1)-dependent transcription of steroidogenic enzymes in experimental animals [8].
• The nuclear orphan receptors COUP-TF and ARP-1 positively regulate the trout estrogen receptor gene through enhancing autoregulation [18].
• Hepatocyte nuclear factor 4 (HNF4) and chicken ovalbumin upstream promoter transcription factor II (COUP-TFII) synergistically activate transcription of the CYP7A1 promoter [19].
• Luciferase reporter assays indicated that COUP-TFII could suppress the transcription of hTERT promoter, and the inhibition to some extent could be reversed by co-transfection of c-myc [17].

Other interactions of NR2F2

• The orphan receptor ARP-1/COUP-TFII, a member of the chicken ovalbumin upstream promoter transcription factor (COUP-TF) subfamily of nuclear receptors, strongly represses transcriptional activity of numerous genes, including several apolipoprotein-encoding genes [1].
• HNF-4 and ARP-1 bind with similar affinities to the C3P site, suggesting that their opposing transcriptional effects may be mediated by direct competition for DNA binding [20].
• In the reproductive and endocrine systems, COUP-TFII immunoreactivity was detected in the stroma, vascular endothelium and smooth muscle, while it was less frequent in adrenal 4 binding protein (Ad4BP) positive steroidogenic cells [13].
• Furthermore, cotreatment with UO126 prevented induction of COUP-TFII expression by EGF in MCF-7 cells [2].
• Treatment of MCF-7 cells with OSM resulted in an approximately 90% reduction of COUP-TFII mRNA expression [2].

Analytical, diagnostic and therapeutic context of NR2F2

• Here, we demonstrate by a combination of antisense and chromatin immunoprecipitation (ChIP) analysis that E1A-12 is a physical component of the class I enhancer repression complex, known to comprise COUP-TFII and histone deacetylase 1 (HDAC1) [21].
• Immunofluorescence microscopy using a total of six antibodies generated against the p150Glued, Arp1 and dynamitin subunits of dynactin revealed a novel fraction of dynactin-positive structures aligned in linear arrays along the distal segments of interphase microtubules [22].
• Co-immunoprecipitation assays using ARP-1-selective antibodies revealed specific physical interactions between ARP-1 and the basal transcription factor TFIIB [23].
• Using reverse transcription-polymerase chain reaction (RT-PCR), Sp17 transcripts were detected in ARK-B, ARP-1, RPMI-8226 and KMS-11 but not in H929, IM-9, MM1-R and U266 cells [24].
• The role of COUP-TFII in both hTERT transcription and telomerase activity were probed through Luciferase reporter assay, Northern blot, and TRAP-PCR ELISA [25].

References