Disease relevance of NR2F1

• COUP-TFI expression in human adrenocortical adenomas: possible role in steroidogenesis [1].
• In transiently transfected MCF-7 human breast cancer cells, overexpression of COUP-TFI inhibited TCDD-activated reporter gene activity from the CYP1A1 promoter [2].
• To clarify the mechanisms of COUP-TF-mediated repression, we therefore screened for COUP-TF-interacting proteins using a yeast two-hybrid system from a cortisol-producing adenoma cDNA library [3].
• Modulation of retinoic acid sensitivity in lung cancer cells through dynamic balance of orphan receptors nur77 and COUP-TF and their heterodimerization [4].
• Here, we have examined the role of COUP-TF in microglial cells, the major target cells for HIV-1 infection in brain [5].

High impact information on NR2F1

• In this paper, the purine base and the phosphate backbone contact sites for the COUP transcription factor were defined [6].
• COUP transcription factor is a member of the steroid receptor superfamily [7].
• COUP-TF also binds specifically to the rat insulin promoter element, although the two binding sites share little sequence similarity [7].
• Comparison of the amino-acid sequence of COUP-TF with known sequences reveals that it is a member of the steroid/thyroid hormone/vitamin receptor superfamily [7].
• Stable expression of COUP-TF in nur77-positive, RA-resistant lung cancer cells enhances the inducibility of RARbeta gene expression and growth inhibition by RA [4].

Chemical compound and disease context of NR2F1

• These results reveal the importance of COUP-TF and the dopamine signaling pathway as activators of human immunodeficiency virus type 1 gene expression in brain [8].
• Chicken ovalbumin upstream promoter transcription factor (COUP-TF): an orphan steroid receptor with a specific pattern of differential expression in human ovarian cancer cell lines [9].
• Expression of retinoid X receptors and COUP-TFI in a human salivary gland adenocarcinoma cell line [10].
• In endometriosis, however, an aberrantly expressed factor, SF-1, displaces COUP-TF to bind to this same promoter and activates aromatase expression and thus local estrogen biosynthesis [11].

Biological context of NR2F1

• Furthermore, we demonstrate interaction of TFIIB with Sp1/Sp3 at the Sp1(I) site besides its association with EAR3 and the TATA-less core promoter region [12].
• Here we show that the same region of COUP-TFI, located between amino acids 184 and 423, is involved in these three mechanisms of transactivation by COUP-TFI [13].
• The stimulation was reversed by coexpression of EAR2 or EAR3/COUP-TFI, indicating their competitive binding for this site [14].
• Thus, COUP-TF and SF-1 act as a transcriptional repressor and activator, respectively, of CYP17 gene expression [1].
• High COUP-TFI expression was associatedwith a nonfunctioning phenotype [1].

Anatomical context of NR2F1

• In addition, hCG treatment significantly reduced the inhibition of rLHR gene in granulosa cells and also decreased EAR2 and EAR3/COUP-TFI protein levels [15].
• These in vitro data indicate that COUP-TF proteins and SMRT modulate PPARgamma-mediated LPL transcription in the 293T cell line [16].
• Synergistic activation of the Atlantic salmon hepatocyte nuclear factor (HNF) 1 promoter by the orphan nuclear receptors HNF4 and chicken ovalbumin upstream promoter transcription factor I (COUP-TFI) [17].
• To address this apparent paradox, the current study examined the effect of two classes of candidate comodulatory proteins, COUP-TF (chicken ovalbumin upstream promoter transcriptional factor) and the corepressor SMRT (silencing mediator of retinoic acid receptor and thyroid receptor) [16].
• Expression profiles of COUP-TF, DAX-1, and SF-1 in the human adrenal gland and adrenocortical tumors: possible implications in steroidogenesis [18].

Associations of NR2F1 with chemical compounds

• In addition, COUP-TF1 binds to DNA elements in certain genes and transactivates directly [13].
• TCDD inhibited estradiol (E(2))-activated reporter gene activity from a consensus ERE and from the EREs in the pS2 and Fos genes, and COUP-TFI did not block the antiestrogenic activity of TCDD [2].
• Unliganded retinoid receptor heterodimers had the same helper function as COUP-TF in the presence of estradiol but were switched to repressors when the ligand all-trans-retinoic acid was added [19].
• When ER was liganded by the antiestrogen 4-hydroxytamoxifen (4-OHT), COUP-TF-half-site interaction decreased [20].
• When the COUP-TF orphan receptor was cotransfected, the 9-cis-RA-induced RXR homodimer activity was strongly repressed [21].

Physical interactions of NR2F1

• We also report that AHR interacts with COUP-TF in transfected CV-1 cells [2].
• These results demonstrate that CTIP1 is a sequence-specific DNA binding protein and a bona fide transcriptional repressor that is capable of functioning independently of COUP-TF family members [22].
• Conversely, COUP-TF enhanced the ERE binding of purified E2-ER, but did not affect TAz-ER-ERE binding [23].
• By mutation analysis, we demonstrate that the effect of COUP-TF requires its binding to a DR-8 element present in the RARbeta promoter [24].
• We further demonstrate that NF-IL6 physically interacts with the nuclear receptor chicken ovalbumin upstream promoter transcription factor (COUP-TF), via its DNA binding domain, in vitro and in cells, which results in mutual transcriptional repression [25].

Regulatory relationships of NR2F1

• Notably, COUP-TFI activated rather than repressed several target genes including the human CYP11B2 gene promoter, the results of which were opposite to those of the CYP17 promoter [26].
• Co-transfection of ER-expressing MCF-7 human breast cancer cells with an expression vector for COUP-TFI resulted in a dose-dependent inhibition of E2-induced expression of a luciferase reporter gene under the control of three tandem copies of EREc38 [20].
• We report that CTIP2 represses Sp1- and COUP-TF-mediated activation of HIV-1 gene transcription and viral replication as a result of physical interactions with COUP-TF and Sp1 in microglial nuclei [27].
• In a transient transfection assay, COUP-TF strongly induced transcriptional activity of the RARbeta promoter in a RA- and RARalpha-dependent manner [24].
• In human lung cancer cell lines, COUP-TF is highly expressed in RA-sensitive cell lines while nur77 expression is associated with RA resistance [4].

Other interactions of NR2F1

• 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 [28].
• Although S300-II does not bind DNA selectively, it stabilizes the binding of COUP-TF to its ciselement (Tsai, S. Y., Sagami, I., Wang, H., Tsai, M.-J., and O'Malley, B. W. (1987) Cell 50, 701-709) [29].
• The aryl hydrocarbon receptor interacts with estrogen receptor alpha and orphan receptors COUP-TFI and ERRalpha1 [2].
• In summary, the results indicate that co-localization of COUP-TF, DAX-1, and SF-1 in NL was lost in adrenocortical tumors and that these orphan receptors play an important role in the regulation of steroidogenesis in human adrenals [18].
• We report that AHR interacts directly with ERalpha, COUP-TF, and ERRalpha1, in a ligand-specific manner in vitro [2].

Analytical, diagnostic and therapeutic context of NR2F1

• In gel mobility shift assays, COUP-TF bound as an apparent dimer to ERE and ERE half-sites [20].
• Chromatin immunoprecipitation analysis of apo A1 transcription complexes from control and ligand-activated cells showed an increase in the binding of reported apo A1 transcriptional inhibitor COUP-TF, which competes with HNF4 for DNA binding [30].
• Co-immunoprecipitation assays showed that ER and COUP-TF interact in extracts from MCF-7 and ERalpha-transfected MDA-MB-231 cells [23].
• Results from reverse transcription-polymerase chain reaction and immunocytochemistry analysis further revealed the importance of this factor by demonstrating that overexpression of COUP-TF leads to initiation of viral replication in primary HIV-infected human microglia [31].
• In contrast to the mouse lactoferrin COUP/ERE element, COUP-TF does not interact with this element, as demonstrated by band shift assay and site-directed mutagenesis [32].

References