Nuclear receptor coactivator 1

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The nuclear receptor coactivator 1 (NCOA1) is a transcriptional coregulatory protein that contains several nuclear receptor interacting domains and an intrinsic histone acetyltransferase activity (EC 2.3.1.48). NCOA1 is recruited to DNA promotion sites by ligand-activated nuclear receptors. NCOA1, in turn, acylates histones, which makes downstream DNA more accessible to transcription. Hence, NCOA1 assists nuclear receptors in the upregulation of DNA expression.[1][2]

NCOA1 is also frequently called steroid receptor coactivator-1 (SRC-1).

## Contents

* 1 Interactions
* 2 References
* 3 External links
* 4 Further reading

## Interactions

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Nuclear receptor coactivator 1 possesses a basic helix-loop-helix (bHLH) domain and has been shown to interact with:

* Androgen receptor,[3][4][5]
* C-Fos,[6][7]
* C-jun,[6][7][8]
* CIITA,[9]
* CREB-binding protein,[10][11]
* Cyclin D1,[12]
* DDX17,[13]
* DDX5[13] and
* Estrogen receptor alpha,[10][13][14][15][16]
* Glucocorticoid receptor,[17][18]
* NFKB1,[6][19]
* PCAF,[20]
* PPARGC1A,[21]
* Peroxisome proliferator-activated receptor alpha,[22][23]
* SNW1,[24]
* STAT3,[25]
* STAT6,[26][27]
* TRIP4,[28] and
* Thyroid hormone receptor beta.[29][30]

## References

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1. ↑ Oñate SA, Tsai SY, Tsai MJ, O'Malley BW (1995). "Sequence and characterization of a coactivator for the steroid hormone receptor superfamily". Science. 270 (5240): 1354–1357. doi:10.1126/science.270.5240.1354. PMID 7481822.
2. ↑ Onate SA, Boonyaratanakornkit V, Spencer TE, Tsai SY, Tsai MJ, Edwards DP, O'Malley BW (1998). "The steroid receptor coactivator-1 contains multiple receptor interacting and activation domains that cooperatively enhance the activation function 1 (AF1) and AF2 domains of steroid receptors". Journal of Biological Chemistry. 273 (20): 12101–12108. doi:10.1074/jbc.273.20.12101. PMID 9575154.
3. ↑ Masiello D, Chen SY, Xu Y, Verhoeven MC, Choi E, Hollenberg AN, Balk SP (Oct 2004). "Recruitment of beta-catenin by wild-type or mutant androgen receptors correlates with ligand-stimulated growth of prostate cancer cells". Molecular Endocrinology. 18 (10): 2388–2401. doi:10.1210/me.2003-0436. PMID 15256534.
4. ↑ Ueda T, Mawji NR, Bruchovsky N, Sadar MD (Oct 2002). "Ligand-independent activation of the androgen receptor by interleukin-6 and the role of steroid receptor coactivator-1 in prostate cancer cells". Journal of Biological Chemistry. 277 (41): 38087–38094. doi:10.1074/jbc.M203313200. PMID 12163482.
5. ↑ Bevan CL, Hoare S, Claessens F, Heery DM, Parker MG (Dec 1999). "The AF1 and AF2 domains of the androgen receptor interact with distinct regions of SRC1". Molecular and Cellular Biology. 19 (12): 8383–8392. doi:10.1128/mcb.19.12.8383. PMC 84931. PMID 10567563.
6. ↑ 6.0 6.1 6.2 Lee SK, Na SY, Jung SY, Choi JE, Jhun BH, Cheong J, Meltzer PS, Lee YC, Lee JW (Jun 2000). "Activating protein-1, nuclear factor-kappaB, and serum response factor as novel target molecules of the cancer-amplified transcription coactivator ASC-2". Molecular Endocrinology. 14 (6): 915–925. doi:10.1210/mend.14.6.0471. PMID 10847592.
7. ↑ 7.0 7.1 Lee SK, Kim HJ, Na SY, Kim TS, Choi HS, Im SY, Lee JW (Jul 1998). "Steroid receptor coactivator-1 coactivates activating protein-1-mediated transactivations through interaction with the c-Jun and c-Fos subunits". Journal of Biological Chemistry. 273 (27): 16651–16654. doi:10.1074/jbc.273.27.16651. PMID 9642216.
8. ↑ Lee SK, Anzick SL, Choi JE, Bubendorf L, Guan XY, Jung YK, Kallioniemi OP, Kononen J, Trent JM, Azorsa D, Jhun BH, Cheong JH, Lee YC, Meltzer PS, Lee JW (Nov 1999). "A nuclear factor, ASC-2, as a cancer-amplified transcriptional coactivator essential for ligand-dependent transactivation by nuclear receptors in vivo". Journal of Biological Chemistry. 274 (48): 34283–34293. doi:10.1074/jbc.274.48.34283. PMID 10567404.
9. ↑ Tzortzakaki E, Spilianakis C, Zika E, Kretsovali A, Papamatheakis J (Dec 2003). "Steroid receptor coactivator 1 links the steroid and interferon gamma response pathways". Molecular Endocrinology. 17 (12): 2509–2518. doi:10.1210/me.2002-0439. PMID 12933903.
10. ↑ 10.0 10.1 Sheppard HM, Harries JC, Hussain S, Bevan C, Heery DM (Jan 2001). "Analysis of the steroid receptor coactivator 1 (SRC1)-CREB binding protein interaction interface and its importance for the function of SRC1". Molecular and Cellular Biology. 21 (1): 39–50. doi:10.1128/MCB.21.1.39-50.2001. PMC 86566. PMID 11113179.
11. ↑ Wu RC, Qin J, Hashimoto Y, Wong J, Xu J, Tsai SY, Tsai MJ, O'Malley BW (May 2002). "Regulation of SRC-3 (pCIP/ACTR/AIB-1/RAC-3/TRAM-1) Coactivator activity by I kappa B kinase". Molecular and Cellular Biology. 22 (10): 3549–3461. doi:10.1128/MCB.22.10.3549-3561.2002. PMC 133790. PMID 11971985.
12. ↑ Zwijsen RM, Buckle RS, Hijmans EM, Loomans CJ, Bernards R (Nov 1998). "Ligand-independent recruitment of steroid receptor coactivators to estrogen receptor by cyclin D1". Genes & Development. 12 (22): 3488–3498. doi:10.1101/gad.12.22.3488. PMC 317237. PMID 9832502.
13. ↑ 13.0 13.1 13.2 Watanabe M, Yanagisawa J, Kitagawa H, Takeyama K, Ogawa S, Arao Y, Suzawa M, Kobayashi Y, Yano T, Yoshikawa H, Masuhiro Y, Kato S (Mar 2001). "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 Journal. 20 (6): 1341–1352. doi:10.1093/emboj/20.6.1341. PMC 145523. PMID 11250900.
14. ↑ DiRenzo J, Shang Y, Phelan M, Sif S, Myers M, Kingston R, Brown M (Oct 2000). "BRG-1 is recruited to estrogen-responsive promoters and cooperates with factors involved in histone acetylation". Molecular and Cellular Biology. 20 (20): 7541–7549. doi:10.1128/MCB.20.20.7541-7549.2000. PMC 86306. PMID 11003650.
15. ↑ Kalkhoven E, Valentine JE, Heery DM, Parker MG (Jan 1998). "Isoforms of steroid receptor co-activator 1 differ in their ability to potentiate transcription by the oestrogen receptor". EMBO Journal. 17 (1): 232–243. doi:10.1093/emboj/17.1.232. PMC 1170374. PMID 9427757.
16. ↑ Kang YK, Guermah M, Yuan CX, Roeder RG (Mar 2002). "The TRAP/Mediator coactivator complex interacts directly with estrogen receptors alpha and beta through the TRAP220 subunit and directly enhances estrogen receptor function in vitro". Proceedings of the National Academy of Sciences, USA. 99 (5): 2642–2647. doi:10.1073/pnas.261715899. PMC 122401. PMID 11867769.
17. ↑ Zilliacus J, Holter E, Wakui H, Tazawa H, Treuter E, Gustafsson JA (Apr 2001). "Regulation of glucocorticoid receptor activity by 14--3-3-dependent intracellular relocalization of the corepressor RIP140". Molecular Endocrinology. 15 (4): 501–511. doi:10.1210/mend.15.4.0624. PMID 11266503.
18. ↑ Kucera T, Waltner-Law M, Scott DK, Prasad R, Granner DK (Jul 2002). "A point mutation of the AF2 transactivation domain of the glucocorticoid receptor disrupts its interaction with steroid receptor coactivator 1". Journal of Biological Chemistry. 277 (29): 26098–260102. doi:10.1074/jbc.M204013200. PMID 12118039.
19. ↑ Na SY, Lee SK, Han SJ, Choi HS, Im SY, Lee JW (May 1998). "Steroid receptor coactivator-1 interacts with the p50 subunit and coactivates nuclear factor kappaB-mediated transactivations". Journal of Biological Chemistry. 273 (18): 10831–10834. doi:10.1074/jbc.273.18.10831. PMID 9556555.
20. ↑ Spencer TE, Jenster G, Burcin MM, Allis CD, Zhou J, Mizzen CA, McKenna NJ, Onate SA, Tsai SY, Tsai MJ, O'Malley BW (Sep 1997). "Steroid receptor coactivator-1 is a histone acetyltransferase". Nature. 389 (6647): 194–198. doi:10.1038/38304. PMID 9296499.
21. ↑ Puigserver P, Adelmant G, Wu Z, Fan M, Xu J, O'Malley B, Spiegelman BM (Nov 1999). "Activation of PPARgamma coactivator-1 through transcription factor docking". Science. 286 (5443): 1368–1371. doi:10.1126/science.286.5443.1368. PMID 10558993.
22. ↑ Dowell P, Ishmael JE, Avram D, Peterson VJ, Nevrivy DJ, Leid M (Dec 1997). "p300 functions as a coactivator for the peroxisome proliferator-activated receptor alpha". Journal of Biological Chemistry. 272 (52): 33435–33443. doi:10.1074/jbc.272.52.33435. PMID 9407140.
23. ↑ Treuter E, Albrektsen T, Johansson L, Leers J, Gustafsson JA (Jun 1998). "A regulatory role for RIP140 in nuclear receptor activation". Molecular Endocrinology. 12 (6): 864–881. doi:10.1210/mend.12.6.0123. PMID 9626662.
24. ↑ Zhang C, Baudino TA, Dowd DR, Tokumaru H, Wang W, MacDonald PN (Nov 2001). "Ternary complexes and cooperative interplay between NCoA-62/Ski-interacting protein and steroid receptor coactivators in vitamin D receptor-mediated transcription". Journal of Biological Chemistry. 276 (44): 40614–40620. doi:10.1074/jbc.M106263200. PMID 11514567.
25. ↑ Giraud S, Bienvenu F, Avril S, Gascan H, Heery DM, Coqueret O (Mar 2002). "Functional interaction of STAT3 transcription factor with the coactivator NcoA/SRC1a". Journal of Biological Chemistry. 277 (10): 8004–811. doi:10.1074/jbc.M111486200. PMID 11773079.
26. ↑ Litterst CM, Pfitzner E (Dec 2001). "Transcriptional activation by STAT6 requires the direct interaction with NCoA-1". Journal of Biological Chemistry. 276 (49): 45713–45721. doi:10.1074/jbc.M108132200. PMID 11574547.
27. ↑ Litterst CM, Pfitzner E (Sep 2002). "An LXXLL motif in the transactivation domain of STAT6 mediates recruitment of NCoA-1/SRC-1". Journal of Biological Chemistry. 277 (39): 36052–36060. doi:10.1074/jbc.M203556200. PMID 12138096.
28. ↑ Kim HJ, Yi JY, Sung HS, Moore DD, Jhun BH, Lee YC, Lee JW (Sep 1999). "Activating signal cointegrator 1, a novel transcription coactivator of nuclear receptors, and its cytosolic localization under conditions of serum deprivation". Molecular and Cellular Biology. 19 (9): 6323–6332. doi:10.1128/mcb.19.9.6323. PMC 84603. PMID 10454579.
29. ↑ Liu Y, Takeshita A, Misiti S, Chin WW, Yen PM (Oct 1998). "Lack of coactivator interaction can be a mechanism for dominant negative activity by mutant thyroid hormone receptors". Endocrinology. 139 (10): 4197–4204. doi:10.1210/endo.139.10.6218. PMID 9751500.
30. ↑ Jeyakumar M, Tanen MR, Bagchi MK (Jun 1997). "Analysis of the functional role of steroid receptor coactivator-1 in ligand-induced transactivation by thyroid hormone receptor". Molecular Endocrinology. 11 (6): 755–767. doi:10.1210/mend.11.6.0003. PMID 9171239.

## External links

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* nuclear receptor coactivator 1 at the US National Library of Medicine Medical Subject Headings (MeSH)
* NURSA C89

## Further reading

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* Qi C, Zhu Y, Reddy JK (2001). "Peroxisome proliferator-activated receptors, coactivators, and downstream targets". Cell Biochemistry and Biophysics. 32. Spring: 187–204. PMID 11330046.

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PDB gallery

* 1oj5: CRYSTAL STRUCTURE OF THE NCO-A1 PAS-B DOMAIN BOUND TO THE STAT6 TRANSACTIVATION DOMAIN LXXLL MOTIF

1oj5: CRYSTAL STRUCTURE OF THE NCO-A1 PAS-B DOMAIN BOUND TO THE STAT6 TRANSACTIVATION DOMAIN LXXLL MOTIF

* 2c52: STRUCTURAL DIVERSITY IN CBP P160 COMPLEXES

2c52: STRUCTURAL DIVERSITY IN CBP P160 COMPLEXES

* 2prg: LIGAND-BINDING DOMAIN OF THE HUMAN PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA

2prg: LIGAND-BINDING DOMAIN OF THE HUMAN PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA

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Transcription coregulators

Coactivators|

* ARA (54, 55, 70)
* BCAS3
* CARM1
* p300-CBP (EP300, CREBBP)
* CRTC (1, 2, 3)
* DRIP/TRAP (MED1 Drip205/Trap220)
* MN1
* PCAF
* PNRC (1, 2)
* PPARGC (1A, 1B)
* TGFB1I1
NCOA1 (SRC-1)
* NCOA2 (GRIP1/SRC-2/TIF2)
* NCOA3 (AIB/SRC-3/TRAM-1)
* NCOA4 (ARA70)
* NCOA5 (CIA)
* NCOA6 (RAP250)
* NCOA7 (ERAP140)

Corepressors|

* CTBP (1, 2)
* Hairless homolog
* LCOR
* NRIP1 (RIP140)
* PELP-1
* RCOR1
* Rb
* SIN3A
* SIN3B
* Tripartite motif family TRIM (24, 28, 33)
NCOR1
* NCOR2 (SMRT)

ATP-dependent remodeling factors|

* Chromatin Structure Remodeling (RSC) Complex
* SWI/SNF

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