Nuclear receptor coactivator 1 explained

The nuclear receptor coactivator 1 (NCOA1), also called steroid receptor coactivator-1 (SRC-1), is a transcriptional coregulatory protein that contains several nuclear receptor–interacting domains and possesses intrinsic histone acetyltransferase activity.^{[1] [2]} It is encoded by the gene NCOA1.^[3]

NCOA1 is recruited to DNA promoter 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 as a coactivator.^{[1] [2]}

Interactions

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

• Androgen receptor,^{[4] [5] [6]}
• C-Fos,^{[7] [8]}
• C-jun,^{[7] [8] [9]}
• CIITA,^[10]
• CREB-binding protein,^{[11] [12]}
• Cyclin D1,^[13]
• DDX17,^[14]
• DDX5^[14] and
• Estrogen receptor alpha,^{[11] [14] [15] [16] [17]}
• Glucocorticoid receptor,^{[18] [19]}
• NFKB1,^{[7] [20]}
• PCAF,^[21]
• PPARGC1A,^[22]
• Peroxisome proliferator-activated receptor alpha,^{[23] [24]}
• SNW1,^[25]
• STAT3,^[26]
• STAT6,^{[27] [28]}
• TRIP4,^[29] and
• Thyroid hormone receptor beta.^{[30] [31]}

Further reading

• Qi C, Zhu Y, Reddy JK . Peroxisome proliferator-activated receptors, coactivators, and downstream targets . . Spring . 1–3. 187–204 . 2001 . 11330046 . 10.1385/cbb:32:1-3:187. 32 . 31795393 .

Notes and References

1. Ming-Jer Tsai . Oñate SA, Tsai SY, Tsai MJ, O'Malley BW . Sequence and characterization of a coactivator for the steroid hormone receptor superfamily . Science . 270 . 5240 . 1354–1357 . 1995 . 7481822 . 10.1126/science.270.5240.1354 . 1995Sci...270.1354O . 28749162 .
2. Onate SA, Boonyaratanakornkit V, Spencer TE, Tsai SY, Tsai MJ, Edwards DP, O'Malley BW . 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 . 1998 . 9575154 . 10.1074/jbc.273.20.12101 . free .
3. Web site: NCOA1 Gene - Nuclear Receptor Coactivator 1. GeneCards: The Human Gene Database. 4 October 2023. 22 November 2023.
4. Masiello D, Chen SY, Xu Y, Verhoeven MC, Choi E, Hollenberg AN, Balk SP . 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 . Oct 2004 . 15256534 . 10.1210/me.2003-0436 . free .
5. Ueda T, Mawji NR, Bruchovsky N, Sadar MD . 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 . Oct 2002 . 12163482 . 10.1074/jbc.M203313200 . free .
6. Bevan CL, Hoare S, Claessens F, Heery DM, Parker MG . The AF1 and AF2 domains of the androgen receptor interact with distinct regions of SRC1 . Molecular and Cellular Biology . 19 . 12 . 8383–8392 . Dec 1999 . 10567563 . 84931 . 10.1128/mcb.19.12.8383.
7. Lee SK, Na SY, Jung SY, Choi JE, Jhun BH, Cheong J, Meltzer PS, Lee YC, Lee JW . 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 . Jun 2000 . 10847592 . 10.1210/mend.14.6.0471 . free .
8. Lee SK, Kim HJ, Na SY, Kim TS, Choi HS, Im SY, Lee JW . 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 . Jul 1998 . 9642216 . 10.1074/jbc.273.27.16651 . free .
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11. Sheppard HM, Harries JC, Hussain S, Bevan C, Heery DM . 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 . Jan 2001 . 11113179 . 86566 . 10.1128/MCB.21.1.39-50.2001 .
12. Wu RC, Qin J, Hashimoto Y, Wong J, Xu J, Tsai SY, Tsai MJ, O'Malley BW . 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 . May 2002 . 11971985 . 133790 . 10.1128/MCB.22.10.3549-3561.2002 .
13. Zwijsen RM, Buckle RS, Hijmans EM, Loomans CJ, Bernards R . Ligand-independent recruitment of steroid receptor coactivators to estrogen receptor by cyclin D1 . Genes & Development . 12 . 22 . 3488–3498 . Nov 1998 . 9832502 . 317237 . 10.1101/gad.12.22.3488 .
14. 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 Journal . 20 . 6 . 1341–1352 . Mar 2001 . 11250900 . 145523 . 10.1093/emboj/20.6.1341 .
15. DiRenzo J, Shang Y, Phelan M, Sif S, Myers M, Kingston R, Brown M . BRG-1 is recruited to estrogen-responsive promoters and cooperates with factors involved in histone acetylation . Molecular and Cellular Biology . 20 . 20 . 7541–7549 . Oct 2000 . 11003650 . 86306 . 10.1128/MCB.20.20.7541-7549.2000 .
16. Kalkhoven E, Valentine JE, Heery DM, Parker MG . Isoforms of steroid receptor co-activator 1 differ in their ability to potentiate transcription by the oestrogen receptor . EMBO Journal . 17 . 1 . 232–243 . Jan 1998 . 9427757 . 1170374 . 10.1093/emboj/17.1.232 .
17. Kang YK, Guermah M, Yuan CX, Roeder RG . 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 . Mar 2002 . 11867769 . 122401 . 10.1073/pnas.261715899 . 2002PNAS...99.2642K . free .
18. 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 . Molecular Endocrinology . 15 . 4 . 501–511 . Apr 2001 . 11266503 . 10.1210/mend.15.4.0624 . free .
19. Kucera T, Waltner-Law M, Scott DK, Prasad R, Granner DK . 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 . Jul 2002 . 12118039 . 10.1074/jbc.M204013200 . free .
20. Na SY, Lee SK, Han SJ, Choi HS, Im SY, Lee JW . Steroid receptor coactivator-1 interacts with the p50 subunit and coactivates nuclear factor kappaB-mediated transactivations . Journal of Biological Chemistry . 273 . 18 . 10831–10834 . May 1998 . 9556555 . 10.1074/jbc.273.18.10831 . free .
21. Spencer TE, Jenster G, Burcin MM, Allis CD, Zhou J, Mizzen CA, McKenna NJ, Onate SA, Tsai SY, Tsai MJ, O'Malley BW . Steroid receptor coactivator-1 is a histone acetyltransferase . Nature . 389 . 6647 . 194–198 . Sep 1997 . 9296499 . 10.1038/38304 . 1997Natur.389..194S . 4404530 .
22. Puigserver P, Adelmant G, Wu Z, Fan M, Xu J, O'Malley B, Spiegelman BM . Activation of PPARgamma coactivator-1 through transcription factor docking . Science . 286 . 5443 . 1368–1371 . Nov 1999 . 10558993 . 10.1126/science.286.5443.1368 .
23. Dowell P, Ishmael JE, Avram D, Peterson VJ, Nevrivy DJ, Leid M . p300 functions as a coactivator for the peroxisome proliferator-activated receptor alpha . Journal of Biological Chemistry . 272 . 52 . 33435–33443 . Dec 1997 . 9407140 . 10.1074/jbc.272.52.33435 . free .
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25. 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 . Journal of Biological Chemistry . 276 . 44 . 40614–40620 . Nov 2001 . 11514567 . 10.1074/jbc.M106263200 . free .
26. Giraud S, Bienvenu F, Avril S, Gascan H, Heery DM, Coqueret O . Functional interaction of STAT3 transcription factor with the coactivator NcoA/SRC1a . Journal of Biological Chemistry . 277 . 10 . 8004–811 . Mar 2002 . 11773079 . 10.1074/jbc.M111486200 . free .
27. Litterst CM, Pfitzner E . Transcriptional activation by STAT6 requires the direct interaction with NCoA-1 . Journal of Biological Chemistry . 276 . 49 . 45713–45721 . Dec 2001 . 11574547 . 10.1074/jbc.M108132200 . free .
28. Litterst CM, Pfitzner E . An LXXLL motif in the transactivation domain of STAT6 mediates recruitment of NCoA-1/SRC-1 . Journal of Biological Chemistry . 277 . 39 . 36052–36060 . Sep 2002 . 12138096 . 10.1074/jbc.M203556200 . free .
29. Kim HJ, Yi JY, Sung HS, Moore DD, Jhun BH, Lee YC, Lee JW . 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 . Sep 1999 . 10454579 . 84603 . 10.1128/mcb.19.9.6323.
30. Liu Y, Takeshita A, Misiti S, Chin WW, Yen PM . Lack of coactivator interaction can be a mechanism for dominant negative activity by mutant thyroid hormone receptors . Endocrinology . 139 . 10 . 4197–4204 . Oct 1998 . 9751500 . 10.1210/endo.139.10.6218 . free .
31. Jeyakumar M, Tanen MR, Bagchi MK . Analysis of the functional role of steroid receptor coactivator-1 in ligand-induced transactivation by thyroid hormone receptor . Molecular Endocrinology . 11 . 6 . 755–767 . Jun 1997 . 9171239 . 10.1210/mend.11.6.0003 . free .