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Gene Review

NR2F2  -  nuclear receptor subfamily 2, group F,...

Homo sapiens

Synonyms: ARP-1, ARP1, Apolipoprotein A-I regulatory protein 1, CHTD4, COUP transcription factor 2, ...
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Disease relevance of NR2F2


High impact information on NR2F2


Chemical compound and disease context of NR2F2


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


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


  1. Functional domains of the human orphan receptor ARP-1/COUP-TFII involved in active repression and transrepression. Achatz, G., Hölzl, B., Speckmayer, R., Hauser, C., Sandhofer, F., Paulweber, B. Mol. Cell. Biol. (1997) [Pubmed]
  2. Activation of the MAP kinase pathway induces chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) expression in human breast cancer cell lines. Moré, E., Fellner, T., Doppelmayr, H., Hauser-Kronberger, C., Dandachi, N., Obrist, P., Sandhofer, F., Paulweber, B. J. Endocrinol. (2003) [Pubmed]
  3. Transactivation of the human apolipoprotein CII promoter by orphan and ligand-dependent nuclear receptors. The regulatory element CIIC is a thyroid hormone response element. Kardassis, D., Sacharidou, E., Zannis, V.I. J. Biol. Chem. (1998) [Pubmed]
  4. Chicken ovalbumin upstream promoter transcription factor II in the human adrenal cortex and its disorders. Suzuki, T., Takahashi, K., Darnel, A.D., MoriyaT, n.u.l.l., Murakami, O., Narasaka, T., Takeyama, J., Sasano, H. J. Clin. Endocrinol. Metab. (2000) [Pubmed]
  5. Repression by ARP-1 sensitizes apolipoprotein AI gene responsiveness to RXR alpha and retinoic acid. Widom, R.L., Rhee, M., Karathanasis, S.K. Mol. Cell. Biol. (1992) [Pubmed]
  6. Regulation of the apolipoprotein AI gene by ARP-1, a novel member of the steroid receptor superfamily. Ladias, J.A., Karathanasis, S.K. Science (1991) [Pubmed]
  7. PC cell-derived growth factor confers resistance to dexamethasone and promotes tumorigenesis in human multiple myeloma. Wang, W., Hayashi, J., Serrero, G. Clin. Cancer Res. (2006) [Pubmed]
  8. Immunolocalization of nuclear transcription factors, DAX-1 and COUP-TF II, in the normal human ovary: correlation with adrenal 4 binding protein/steroidogenic factor-1 immunolocalization during the menstrual cycle. Sato, Y., Suzuki, T., Hidaka, K., Sato, H., Ito, K., Ito, S., Sasano, H. J. Clin. Endocrinol. Metab. (2003) [Pubmed]
  9. Transcriptional regulation of the nuclear gene encoding the alpha-subunit of the mammalian mitochondrial F1F0 ATP synthase complex: role for the orphan nuclear receptor, COUP-TFII/ARP-1. Jordan, E.M., Worley, T., Breen, G.A. Biochemistry (2003) [Pubmed]
  10. COUP-TFI and COUP-TFII regulate expression of the NHE through a nuclear hormone responsive element with enhancer activity. Fernandez-Rachubinski, F., Fliegel, L. Eur. J. Biochem. (2001) [Pubmed]
  11. Decreased Chicken Ovalbumin Upstream Promoter Transcription Factor II Expression in Tamoxifen-Resistant Breast Cancer Cells. Riggs, K.A., Wickramasinghe, N.S., Cochrum, R.K., Watts, M.B., Klinge, C.M. Cancer Res. (2006) [Pubmed]
  12. The retinoid X receptor response element in the human aldehyde dehydrogenase 2 promoter is antagonized by the chicken ovalbumin upstream promoter family of orphan receptors. Pinaire, J., Hasanadka, R., Fang, M., Chou, W.Y., Stewart, M.J., Kruijer, W., Crabb, D. Arch. Biochem. Biophys. (2000) [Pubmed]
  13. Immunohistochemical distribution of chicken ovalbumin upstream promoter transcription factor II in human tissues. Suzuki, T., Moriya, T., Darnel, A.D., Takeyama, J., Sasano, H. Mol. Cell. Endocrinol. (2000) [Pubmed]
  14. Isolation of a novel family of C(2)H(2) zinc finger proteins implicated in transcriptional repression mediated by chicken ovalbumin upstream promoter transcription factor (COUP-TF) orphan nuclear receptors. Avram, D., Fields, A., Pretty On Top, K., Nevrivy, D.J., Ishmael, J.E., Leid, M. J. Biol. Chem. (2000) [Pubmed]
  15. Aspergillus fumigatus arp1 modulates conidial pigmentation and complement deposition. Tsai, H.F., Washburn, R.G., Chang, Y.C., Kwon-Chung, K.J. Mol. Microbiol. (1997) [Pubmed]
  16. The orphan receptor COUP-TFII regulates G2/M progression of breast cancer cells by modulating the expression/activity of p21(WAF1/CIP1), cyclin D1, and cdk2. Nakshatri, H., Mendonca, M.S., Bhat-Nakshatri, P., Patel, N.M., Goulet, R.J., Cornetta, K. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  17. The evidences of human orphan receptor COUP-TFII inhibiting telomerase activity through decreasing hTERT transcription. Wang, Q., Bai, Z., Li, X., Hou, L., Zhang, B. Cancer Lett. (2004) [Pubmed]
  18. The nuclear orphan receptors COUP-TF and ARP-1 positively regulate the trout estrogen receptor gene through enhancing autoregulation. Lazennec, G., Kern, L., Valotaire, Y., Salbert, G. Mol. Cell. Biol. (1997) [Pubmed]
  19. HNF4 and COUP-TFII interact to modulate transcription of the cholesterol 7alpha-hydroxylase gene (CYP7A1). Stroup, D., Chiang, J.Y. J. Lipid Res. (2000) [Pubmed]
  20. Antagonism between apolipoprotein AI regulatory protein 1, Ear3/COUP-TF, and hepatocyte nuclear factor 4 modulates apolipoprotein CIII gene expression in liver and intestinal cells. Mietus-Snyder, M., Sladek, F.M., Ginsburg, G.S., Kuo, C.F., Ladias, J.A., Darnell, J.E., Karathanasis, S.K. Mol. Cell. Biol. (1992) [Pubmed]
  21. E1A is the component of the MHC class I enhancer complex that mediates HDAC chromatin repression in adenovirus-12 tumorigenic cells. Zhao, B., Ricciardi, R.P. Virology (2006) [Pubmed]
  22. Colocalization of cytoplasmic dynein with dynactin and CLIP-170 at microtubule distal ends. Vaughan, K.T., Tynan, S.H., Faulkner, N.E., Echeverri, C.J., Vallee, R.B. J. Cell. Sci. (1999) [Pubmed]
  23. Transcriptional activation by the orphan nuclear receptor ARP-1. Malik, S., Karathanasis, S. Nucleic Acids Res. (1995) [Pubmed]
  24. Sp17 gene expression in myeloma cells is regulated by promoter methylation. Wang, Z., Zhang, Y., Ramsahoye, B., Bowen, D., Lim, S.H. Br. J. Cancer (2004) [Pubmed]
  25. Inhibitory role of transcription factor COUP-TFII in expression of hTERT in HeLa cells. Wang, Q., Bai, Z.L., Xuan, L., Hou, L., Zhang, B. Chin. Med. Sci. J. (2004) [Pubmed]
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