Nuclear receptor coactivator 2 explained

The nuclear receptor coactivator 2 also known as NCoA-2 is a protein that in humans is encoded by the NCOA2 gene. NCoA-2 is also frequently called glucocorticoid receptor-interacting protein 1 (GRIP1), steroid receptor coactivator-2 (SRC-2), or transcriptional mediators/intermediary factor 2 (TIF2).

Function

NCoA-2 is a transcriptional coregulatory protein that contains several nuclear receptor interacting domains and an intrinsic histone acetyltransferase activity. NCOA2 is recruited to DNA promotion sites by ligand-activated nuclear receptors. NCOA2 in turn acetylates histones, which makes downstream DNA more accessible to transcription. Hence, NCOA2 assists nuclear receptors in the upregulation of DNA expression.^{[1] [2]}

GRIP1 is a transcriptional co-activator of the glucocorticoid receptor and interferon regulatory factor 1 (IRF1).^[3]

Interactions

Nuclear receptor coactivator 2 has been shown to interact with:

• AR,^{[4] [5] [6] [7] [8]}
• ARNT,^[9]
• BRCA1,^{[10] [11]}
• ESR1,^{[7] [12] [13]}
• NR3C1,^{[14] [15]}
• PPFIA4,^[16]
• RXRA,^[17]
• VDR.^{[7] [18] [19]}

Further reading

• Voegel JJ, Heine MJ, Zechel C, Chambon P, Gronemeyer H . TIF2, a 160 kDa transcriptional mediator for the ligand-dependent activation function AF-2 of nuclear receptors. . EMBO J. . 15 . 14 . 3667–75 . 1996 . 8670870 . 452006 . 10.1002/j.1460-2075.1996.tb00736.x.
• Hong H, Kohli K, Garabedian MJ, Stallcup MR . GRIP1, a transcriptional coactivator for the AF-2 transactivation domain of steroid, thyroid, retinoid, and vitamin D receptors. . Mol. Cell. Biol. . 17 . 5 . 2735–44 . 1997 . 9111344 . 232124 . 10.1128/MCB.17.5.2735.
• Voegel JJ, Heine MJ, Tini M, Vivat V, Chambon P, Gronemeyer H . The coactivator TIF2 contains three nuclear receptor-binding motifs and mediates transactivation through CBP binding-dependent and -independent pathways. . EMBO J. . 17 . 2 . 507–19 . 1998 . 9430642 . 1170401 . 10.1093/emboj/17.2.507 .
• Carapeti M, Aguiar RC, Goldman JM, Cross NC . A novel fusion between MOZ and the nuclear receptor coactivator TIF2 in acute myeloid leukemia. . Blood . 91 . 9 . 3127–33 . 1998 . 9558366 . 10.1182/blood.V91.9.3127. free .
• Fryer CJ, Archer TK . Chromatin remodelling by the glucocorticoid receptor requires the BRG1 complex. . Nature . 393 . 6680 . 88–91 . 1998 . 9590696 . 10.1038/30032 . 1998Natur.393...88F . 2208522 .
• Berrevoets CA, Doesburg P, Steketee K, Trapman J, Brinkmann AO . Functional interactions of the AF-2 activation domain core region of the human androgen receptor with the amino-terminal domain and with the transcriptional coactivator TIF2 (transcriptional intermediary factor2). . Mol. Endocrinol. . 12 . 8 . 1172–83 . 1998 . 9717843 . 10.1210/mend.12.8.0153 . free . 1765/8892 . free .
• Wang JC, Stafford JM, Granner DK . SRC-1 and GRIP1 coactivate transcription with hepatocyte nuclear factor 4. . J. Biol. Chem. . 273 . 47 . 30847–50 . 1998 . 9812974 . 10.1074/jbc.273.47.30847 . 3968904 . free .
• Hong H, Darimont BD, Ma H, Yang L, Yamamoto KR, Stallcup MR . An additional region of coactivator GRIP1 required for interaction with the hormone-binding domains of a subset of nuclear receptors. . J. Biol. Chem. . 274 . 6 . 3496–502 . 1999 . 9920895 . 10.1074/jbc.274.6.3496 . free .
• Chen D, Ma H, Hong H, Koh SS, Huang SM, Schurter BT, Aswad DW, Stallcup MR . Regulation of transcription by a protein methyltransferase. . Science . 284 . 5423 . 2174–7 . 1999 . 10381882 . 10.1126/science.284.5423.2174 .
• Ma H, Hong H, Huang SM, Irvine RA, Webb P, Kushner PJ, Coetzee GA, Stallcup MR . Multiple signal input and output domains of the 160-kilodalton nuclear receptor coactivator proteins. . Mol. Cell. Biol. . 19 . 9 . 6164–73 . 1999 . 10454563 . 84548 . 10.1128/MCB.19.9.6164.
• Atkins GB, Hu X, Guenther MG, Rachez C, Freedman LP, Lazar MA . Coactivators for the orphan nuclear receptor RORalpha. . Mol. Endocrinol. . 13 . 9 . 1550–7 . 1999 . 10.1210/mend.13.9.0343 . 10478845 . free .
• Carrero P, Okamoto K, Coumailleau P, O'Brien S, Tanaka H, Poellinger L . Redox-regulated recruitment of the transcriptional coactivators CREB-binding protein and SRC-1 to hypoxia-inducible factor 1alpha. . Mol. Cell. Biol. . 20 . 1 . 402–15 . 2000 . 10594042 . 85095 . 10.1128/MCB.20.1.402-415.2000 .
• Xie W, Hong H, Yang NN, Lin RJ, Simon CM, Stallcup MR, Evans RM . Constitutive activation of transcription and binding of coactivator by estrogen-related receptors 1 and 2. . Mol. Endocrinol. . 13 . 12 . 2151–62 . 2000 . 10598588 . 10.1210/mend.13.12.0381 . free .
• Naltner A, Ghaffari M, Whitsett JA, Yan C . Retinoic acid stimulation of the human surfactant protein B promoter is thyroid transcription factor 1 site-dependent. . J. Biol. Chem. . 275 . 1 . 56–62 . 2000 . 10617585 . 10.1074/jbc.275.1.56 . free .
• Jimenez-Lara AM, Heine MJ, Gronemeyer H . Cloning of a mouse glucocorticoid modulatory element binding protein, a new member of the KDWK family. . FEBS Lett. . 468 . 2–3 . 203–10 . 2000 . 10692587 . 10.1016/S0014-5793(00)01209-6 . 8161180 . free .
• Poelzl G, Kasai Y, Mochizuki N, Shaul PW, Brown M, Mendelsohn ME . Specific association of estrogen receptor beta with the cell cycle spindle assembly checkpoint protein, MAD2. . Proc. Natl. Acad. Sci. U.S.A. . 97 . 6 . 2836–9 . 2000 . 10706629 . 16016 . 10.1073/pnas.050580997 . 2000PNAS...97.2836P . free .
• Herdick M, Steinmeyer A, Carlberg C . Antagonistic action of a 25-carboxylic ester analogue of 1alpha, 25-dihydroxyvitamin D3 is mediated by a lack of ligand-induced vitamin D receptor interaction with coactivators. . J. Biol. Chem. . 275 . 22 . 16506–12 . 2000 . 10748178 . 10.1074/jbc.M910000199 . free .
• Koh SS, Chen D, Lee YH, Stallcup MR . Synergistic enhancement of nuclear receptor function by p160 coactivators and two coactivators with protein methyltransferase activities. . J. Biol. Chem. . 276 . 2 . 1089–98 . 2001 . 11050077 . 10.1074/jbc.M004228200 . free .
• Park JJ, Irvine RA, Buchanan G, Koh SS, Park JM, Tilley WD, Stallcup MR, Press MF, Coetzee GA . Breast cancer susceptibility gene 1 (BRCAI) is a coactivator of the androgen receptor. . Cancer Res. . 60 . 21 . 5946–9 . 2000 . 11085509 .

Notes and References

1. Voegel JJ, Heine MJ, Zechel C, Chambon P, Gronemeyer H . TIF2, a 160 kDa transcriptional mediator for the ligand-dependent activation function AF-2 of nuclear receptors . EMBO J . 15 . 14 . 3667–75 . 1996 . 8670870 . 452006 . 10.1002/j.1460-2075.1996.tb00736.x.
2. Hong H, Kohli K, Garabedian MJ, Stallcup MR . GRIP1, a transcriptional coactivator for the AF-2 transactivation domain of steroid, thyroid, retinoid, and vitamin D receptors . Mol Cell Biol . 17 . 5 . 2735–44 . 1997 . 9111344 . 232124 . 10.1128/MCB.17.5.2735.
3. Bhandare R, Damera G, Banerjee A, Flammer JR, Keslacy S, Rogatsky I, Panettieri RA, Amrani Y, Tliba O . Glucocorticoid receptor interacting protein-1 restores glucocorticoid responsiveness in steroid-resistant airway structural cells . Am. J. Respir. Cell Mol. Biol. . 42 . 1 . 9–15 . January 2010 . 19805480 . 2809222 . 10.1165/rcmb.2009-0239RC .
4. Song LN, Coghlan M, Gelmann EP . Antiandrogen effects of mifepristone on coactivator and corepressor interactions with the androgen receptor . Mol. Endocrinol. . 18 . 1 . 70–85 . 2004 . 14593076 . 10.1210/me.2003-0189 . free .
5. Ishitani K, Yoshida T, Kitagawa H, Ohta H, Nozawa S, Kato S . p54nrb acts as a transcriptional coactivator for activation function 1 of the human androgen receptor . Biochem. Biophys. Res. Commun. . 306 . 3 . 660–5 . 2003 . 12810069 . 10.1016/S0006-291X(03)01021-0 .
6. Wang Q, Udayakumar TS, Vasaitis TS, Brodie AM, Fondell JD . Mechanistic relationship between androgen receptor polyglutamine tract truncation and androgen-dependent transcriptional hyperactivity in prostate cancer cells . J. Biol. Chem. . 279 . 17 . 17319–28 . 2004 . 14966121 . 10.1074/jbc.M400970200 . free .
7. He B, Wilson EM . Electrostatic modulation in steroid receptor recruitment of LXXLL and FXXLF motifs . Mol. Cell. Biol. . 23 . 6 . 2135–50 . 2003 . 12612084 . 149467 . 10.1128/MCB.23.6.2135-2150.2003 .
8. Bai S, He B, Wilson EM . Melanoma antigen gene protein MAGE-11 regulates androgen receptor function by modulating the interdomain interaction . Mol. Cell. Biol. . 25 . 4 . 1238–57 . 2005 . 15684378 . 548016 . 10.1128/MCB.25.4.1238-1257.2005 .
9. Beischlag TV, Wang S, Rose DW, Torchia J, Reisz-Porszasz S, Muhammad K, Nelson WE, Probst MR, Rosenfeld MG, Hankinson O . Recruitment of the NCoA/SRC-1/p160 family of transcriptional coactivators by the aryl hydrocarbon receptor/aryl hydrocarbon receptor nuclear translocator complex . Mol. Cell. Biol. . 22 . 12 . 4319–33 . 2002 . 12024042 . 133867 . 10.1128/MCB.22.12.4319-4333.2002 .
10. Rodriguez M, Yu X, Chen J, Songyang Z . Phosphopeptide binding specificities of BRCA1 COOH-terminal (BRCT) domains . J. Biol. Chem. . 278 . 52 . 52914–8 . 2003 . 14578343 . 10.1074/jbc.C300407200 . free .
11. Park JJ, Irvine RA, Buchanan G, Koh SS, Park JM, Tilley WD, Stallcup MR, Press MF, Coetzee GA . Breast cancer susceptibility gene 1 (BRCAI) is a coactivator of the androgen receptor . Cancer Res. . 60 . 21 . 5946–9 . 2000 . 11085509 .
12. Wärnmark A, Treuter E, Gustafsson JA, Hubbard RE, Brzozowski AM, Pike AC . Interaction of transcriptional intermediary factor 2 nuclear receptor box peptides with the coactivator binding site of estrogen receptor alpha . J. Biol. Chem. . 277 . 24 . 21862–8 . 2002 . 11937504 . 10.1074/jbc.M200764200 . free .
13. Fenne IS, Hoang T, Hauglid M, Sagen JV, Lien EA, Mellgren G . Recruitment of coactivator glucocorticoid receptor interacting protein 1 to an estrogen receptor transcription complex is regulated by the 3',5'-cyclic adenosine 5'-monophosphate-dependent protein kinase . Endocrinology . 149 . 9 . 4336–45 . 2008 . 18499756 . 10.1210/en.2008-0037 . free .
14. Zilliacus J, Holter E, Wakui H, Tazawa H, Treuter E, Gustafsson JA . Regulation of glucocorticoid receptor activity by 14--3-3-dependent intracellular relocalization of the corepressor RIP140 . Mol. Endocrinol. . 15 . 4 . 501–11 . 2001 . 11266503 . 10.1210/mend.15.4.0624 . free .
15. Bledsoe RK, Montana VG, Stanley TB, Delves CJ, Apolito CJ, McKee DD, Consler TG, Parks DJ, Stewart EL, Willson TM, Lambert MH, Moore JT, Pearce KH, Xu HE . Crystal structure of the glucocorticoid receptor ligand binding domain reveals a novel mode of receptor dimerization and coactivator recognition . Cell . 110 . 1 . 93–105 . 2002 . 12151000 . 10.1016/S0092-8674(02)00817-6 . free .
16. Wyszynski M, Kim E, Dunah AW, Passafaro M, Valtschanoff JG, Serra-Pagès C, Streuli M, Weinberg RJ, Sheng M . Interaction between GRIP and liprin-alpha/SYD2 is required for AMPA receptor targeting . Neuron . 34 . 1 . 39–52 . 2002 . 11931740 . 10.1016/S0896-6273(02)00640-2 . free .
17. Lee WY, Noy N . Interactions of RXR with coactivators are differentially mediated by helix 11 of the receptor's ligand binding domain . Biochemistry . 41 . 8 . 2500–8 . 2002 . 11851396 . 10.1021/bi011764+.
18. Zhang C, Baudino TA, Dowd DR, Tokumaru H, Wang W, MacDonald PN . Ternary complexes and cooperative interplay between NCoA-62/Ski-interacting protein and steroid receptor coactivators in vitamin D receptor-mediated transcription . J. Biol. Chem. . 276 . 44 . 40614–20 . 2001 . 11514567 . 10.1074/jbc.M106263200 . free .
19. Herdick M, Steinmeyer A, Carlberg C . Antagonistic action of a 25-carboxylic ester analogue of 1alpha, 25-dihydroxyvitamin D3 is mediated by a lack of ligand-induced vitamin D receptor interaction with coactivators . J. Biol. Chem. . 275 . 22 . 16506–12 . 2000 . 10748178 . 10.1074/jbc.M910000199 . free .