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]
- DDX17,[12]
- DDX5,[12]
- ESR1,[7] [12] [13] [14] [15]
- NR3C1,[16] [17]
- PPFIA4,[18]
- PPARG,[19]
- RXRA,[20]
- SRA1,[12] and
- VDR.[7] [13] [21] [22]
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 .
- Kodera Y, Takeyama K, Murayama A, Suzawa M, Masuhiro Y, Kato S . Ligand type-specific interactions of peroxisome proliferator-activated receptor gamma with transcriptional coactivators. . J. Biol. Chem. . 275 . 43 . 33201–4 . 2000 . 10944516 . 10.1074/jbc.C000517200 . 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
- 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.
- 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 .
- 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 .
- 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 .
- 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 .
- 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 .
- 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 .
- 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 .
- 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 .
- 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 .
- Watanabe M, Yanagisawa J, Kitagawa H, Takeyama K, Ogawa S, Arao Y, Suzawa M, Kobayashi Y, Yano T, Yoshikawa H, Masuhiro Y, Kato S . A subfamily of RNA-binding DEAD-box proteins acts as an estrogen receptor alpha coactivator through the N-terminal activation domain (AF-1) with an RNA coactivator, SRA . EMBO J. . 20 . 6 . 1341–52 . 2001 . 11250900 . 145523 . 10.1093/emboj/20.6.1341 .
- Kitagawa H, Fujiki R, Yoshimura K, Mezaki Y, Uematsu Y, Matsui D, Ogawa S, Unno K, Okubo M, Tokita A, Nakagawa T, Ito T, Ishimi Y, Nagasawa H, Matsumoto T, Yanagisawa J, Kato S . The chromatin-remodeling complex WINAC targets a nuclear receptor to promoters and is impaired in Williams syndrome . Cell . 113 . 7 . 905–17 . 2003 . 12837248 . 10.1016/S0092-8674(03)00436-7 . free .
- 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 .
- 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 .
- 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 .
- 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 .
- 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 .
- Kodera Y, Takeyama K, Murayama A, Suzawa M, Masuhiro Y, Kato S . Ligand type-specific interactions of peroxisome proliferator-activated receptor gamma with transcriptional coactivators . J. Biol. Chem. . 275 . 43 . 33201–4 . 2000 . 10944516 . 10.1074/jbc.C000517200 . free .
- 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+.
- 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 .
- 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 .