COUP-TFII explained

COUP-TFII (COUP transcription factor 2), also known as NR2F2 (nuclear receptor subfamily 2, group F, member 2) is a protein that in humans is encoded by the NR2F2 gene.^{[1] [2]} The COUP acronym stands for chicken ovalbumin upstream promoter.

Function

COUP-TFII plays a critical role in controlling the development of a number of tissues and organs including heart, blood vessels, muscles and limbs.^{[3] [4]}

The glucocorticoid receptor (GR) stimulates COUP-TFII-induced transactivation while COUP-TFII represses the GR transcriptional activity.^{[5] [6]} COUP-TFII interacts with GATA2 to inhibit adipocyte differentiation.^[7]

Structure and ligands

The structure of COUP-TF2 LBD is known. Retinoic acid, although not at physiological concentrations, activate this receptor.^[8]

Interactions

COUP-TFII has been shown to interact with:

• HDAC1^[9]
• Lck^[10]
• V-erbA-related gene.^[11]
• Nucleolin^[12]

Further reading

• De Martino MU, Alesci S, Chrousos GP, Kino T . Interaction of the glucocorticoid receptor and the chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII): implications for the actions of glucocorticoids on glucose, lipoprotein, and xenobiotic metabolism . Ann. N. Y. Acad. Sci. . 1024 . 1. 72–85 . 2004 . 15265774 . 10.1196/annals.1321.006 . 2004NYASA1024...72D . 20529633 .
• Mietus-Snyder M, Sladek FM, Ginsburg GS, Kuo CF, Ladias JA, Darnell JE, Karathanasis SK . 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 . Mol. Cell. Biol. . 12 . 4 . 1708–18 . 1992 . 1312668 . 369614 . 10.1128/MCB.12.4.1708.
• Wang LH, Ing NH, Tsai SY, O'Malley BW, Tsai MJ . The COUP-TFs compose a family of functionally related transcription factors . Gene Expr. . 1 . 3 . 207–16 . 1992 . 1820218 . 5952191 .
• Ladias JA, Karathanasis SK . Regulation of the apolipoprotein AI gene by ARP-1, a novel member of the steroid receptor superfamily . Science . 251 . 4993 . 561–5 . 1991 . 1899293 . 10.1126/science.1899293 . 1991Sci...251..561L . 37214450 .
• Marcus SL, Winrow CJ, Capone JP, Rachubinski RA . A p56(lck) ligand serves as a coactivator of an orphan nuclear hormone receptor . J. Biol. Chem. . 271 . 44 . 27197–200 . 1996 . 8910285 . 10.1074/jbc.271.44.27197 . free .
• Thénot S, Henriquet C, Rochefort H, Cavaillès V . Differential interaction of nuclear receptors with the putative human transcriptional coactivator hTIF1 . J. Biol. Chem. . 272 . 18 . 12062–8 . 1997 . 9115274 . 10.1074/jbc.272.18.12062 . free .
• Chu K, Zingg HH . The nuclear orphan receptors COUP-TFII and Ear-2 act as silencers of the human oxytocin gene promoter . J. Mol. Endocrinol. . 19 . 2 . 163–72 . 1998 . 9343308 . 10.1677/jme.0.0190163 .
• Bailey P, Sartorelli V, Hamamori Y, Muscat GE . The orphan nuclear receptor, COUP-TF II, inhibits myogenesis by post-transcriptional regulation of MyoD function: COUP-TF II directly interacts with p300 and myoD . Nucleic Acids Res. . 26 . 23 . 5501–10 . 1999 . 9826778 . 147985 . 10.1093/nar/26.23.5501 .
• Avram D, Ishmael JE, Nevrivy DJ, Peterson VJ, Lee SH, Dowell P, Leid M . Heterodimeric Interactions between Chicken Ovalbumin Upstream Promoter-Transcription Factor Family Members ARP1 and Ear2 . J. Biol. Chem. . 274 . 20 . 14331–6 . 1999 . 10318855 . 2823254 . 10.1074/jbc.274.20.14331 . free .
• Smirnov DA, Hou S, Ricciardi RP . Association of histone deacetylase with COUP-TF in tumorigenic Ad12-transformed cells and its potential role in shut-off of MHC class I transcription . Virology . 268 . 2 . 319–28 . 2000 . 10704340 . 10.1006/viro.1999.0181 . free .
• Avram D, Fields A, Pretty On Top K, Nevrivy DJ, Ishmael JE, Leid M . Isolation of a Novel Family of C2H2 Zinc Finger Proteins Implicated in Transcriptional Repression Mediated by Chicken Ovalbumin Upstream Promoter Transcription Factor (COUP-TF) Orphan Nuclear Receptors . J. Biol. Chem. . 275 . 14 . 10315–22 . 2000 . 10744719 . 2819356 . 10.1074/jbc.275.14.10315 . free .
• Jordan EM, Worley T, Breen GA . 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 . Biochemistry . 42 . 9 . 2656–63 . 2003 . 12614160 . 10.1021/bi0268347 .
• Sato Y, Suzuki T, Hidaka K, Sato H, Ito K, Ito S, Sasano H . 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 . J. Clin. Endocrinol. Metab. . 88 . 7 . 3415–20 . 2003 . 12843196 . 10.1210/jc.2002-021723 . free .
• Colland F, Jacq X, Trouplin V, Mougin C, Groizeleau C, Hamburger A, Meil A, Wojcik J, Legrain P, Gauthier JM . Functional Proteomics Mapping of a Human Signaling Pathway . Genome Res. . 14 . 7 . 1324–32 . 2004 . 15231748 . 442148 . 10.1101/gr.2334104 .
• Kurihara I, Shibata H, Kobayashi S, Suda N, Ikeda Y, Yokota K, Murai A, Saito I, Rainey WE, Saruta T . Ubc9 and Protein Inhibitor of Activated STAT 1 Activate Chicken Ovalbumin Upstream Promoter-Transcription Factor I-mediated Human CYP11B2 Gene Transcription . J. Biol. Chem. . 280 . 8 . 6721–30 . 2005 . 15611122 . 10.1074/jbc.M411820200 . free .
• Shibata H, Kobayashi S, Kurihara I, Suda N, Yokota K, Murai A, Ikeda Y, Saito I, Rainey WE, Saruta T . COUP-TF and transcriptional co-regulators in adrenal steroidogenesis . Endocr. Res. . 30 . 4 . 795–801 . 2005 . 15666827 . 10.1081/ERC-200044042 . 37921753 .

Notes and References

1. Web site: Entrez Gene: NR2F2 nuclear receptor subfamily 2, group F, member 2.
2. Qiu Y, Krishnan V, Zeng Z, Gilbert DJ, Copeland NG, Gibson L, Yang-Feng T, Jenkins NA, Tsai MJ, Tsai SY . Isolation, characterization, and chromosomal localization of mouse and human COUP-TF I and II genes . Genomics . 29 . 1 . 240–6 . September 1995 . 8530078 . 10.1006/geno.1995.1237 . free .
3. Ming-Jer Tsai . Pereira FA, Qiu Y, Zhou G, Tsai MJ, Tsai SY . The orphan nuclear receptor COUP-TFII is required for angiogenesis and heart development . Genes Dev. . 13 . 8 . 1037–49 . April 1999 . 10215630 . 316637 . 10.1101/gad.13.8.1037 .
4. Lee CT, Li L, Takamoto N, Martin JF, Demayo FJ, Tsai MJ, Tsai SY . The Nuclear Orphan Receptor COUP-TFII Is Required for Limb and Skeletal Muscle Development . Mol. Cell. Biol. . 24 . 24 . 10835–43 . December 2004 . 15572686 . 533959 . 10.1128/MCB.24.24.10835-10843.2004 .
5. De Martino MU, Bhattachryya N, Alesci S, Ichijo T, Chrousos GP, Kino T . The glucocorticoid receptor and the orphan nuclear receptor chicken ovalbumin upstream promoter-transcription factor II interact with and mutually affect each other's transcriptional activities: implications for intermediary metabolism . Mol. Endocrinol. . 18 . 4 . 820–33 . April 2004 . 14739255 . 10.1210/me.2003-0341 . free .
6. De Martino MU, Alesci S, Chrousos GP, Kino T . Interaction of the glucocorticoid receptor and the chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII): implications for the actions of glucocorticoids on glucose, lipoprotein, and xenobiotic metabolism . Ann. N. Y. Acad. Sci. . 1024 . 1. 72–85 . June 2004 . 15265774 . 10.1196/annals.1321.006 . 2004NYASA1024...72D . 20529633 .
7. Xu Z, Yu S, Hsu CH, Eguchi J, Rosen ED . The orphan nuclear receptor chicken ovalbumin upstream promoter-transcription factor II is a critical regulator of adipogenesis . Proc. Natl. Acad. Sci. U.S.A. . 105 . 7 . 2421–6 . February 2008 . 18250317 . 2268152 . 10.1073/pnas.0707082105 . 2008PNAS..105.2421X . free .
8. Kruse SW, Suino-Powell K, Zhou XE, Kretschman JE, Reynolds R, Vonrhein C, Xu Y, Wang L, Tsai SY, Tsai MJ, Xu HE . 6 . Identification of COUP-TFII orphan nuclear receptor as a retinoic acid-activated receptor . PLOS Biology . 6 . 9 . e227 . September 2008 . 18798693 . 2535662 . 10.1371/journal.pbio.0060227 . free .
9. Smirnov DA, Hou S, Ricciardi RP . Association of histone deacetylase with COUP-TF in tumorigenic Ad12-transformed cells and its potential role in shut-off of MHC class I transcription . Virology . 268 . 2 . 319–28 . March 2000 . 10704340 . 10.1006/viro.1999.0181 . free .
10. Marcus SL, Winrow CJ, Capone JP, Rachubinski RA . A p56(lck) ligand serves as a coactivator of an orphan nuclear hormone receptor . J. Biol. Chem. . 271 . 44 . 27197–200 . November 1996 . 8910285 . 10.1074/jbc.271.44.27197 . free .
11. Avram D, Ishmael JE, Nevrivy DJ, Peterson VJ, Lee SH, Dowell P, Leid M . Heterodimeric Interactions between Chicken Ovalbumin Upstream Promoter-Transcription Factor Family Members ARP1 and Ear2 . J. Biol. Chem. . 274 . 20 . 14331–6 . May 1999 . 10318855 . 2823254 . 10.1074/jbc.274.20.14331 . free .
12. Litchfield LM, Riggs KA, Hockenberry AM, Oliver LD, Barnhart KG, Cai J, Pierce WM, Ivanova MM, Bates PJ, Appana SN, Datta S, Kulesza P, McBryan J, Young LS, Klinge CM . Identification and characterization of nucleolin as a COUP-TFII coactivator of retinoic acid receptor β transcription in breast cancer cells. . PLOS ONE . 7 . 5 . May 2012 . 3365040 . 10.1371/journal.pone.0038278 . 22693611 . e38278. 2012PLoSO...738278L . free .