NCOR2

Correpresor 2 de receptor nuclear
Estructura tridimensional de la proteína NCOR2.
HUGO	7673
Símbolo	NCOR2
Símbolos alt.	CTG26; TNRC14; TRAC1; SMRT; SMRTE; SMRTE-tau; TRAC-1
Datos genéticos
Locus	Cr. 12 q24.31
Bases de datos
Entrez	9612
OMIM	600848
PDB	1xc5
RefSeq	NP_001070729
UniProt	Q9Y618

El correpresor 2 de receptor nuclear (NCOR2) es un corregulador transcripcional codificado en humanos por el gen ncor2, que contiene varios dominios de interacción con receptores nucleares. Además, NCOR2 parece estar implicado en el reclutamiento de las histona deacetilasas hacia regiones promotoras en el ADN. De hecho, NCOR2 ayuda a los receptores nucleares en la regulación de la expresión génica.^{[1] [2]} NCOR2 también es referido como mediador de los receptores de hormona tiroidea y retinoides (SMRT)^[1] y como cofactor 1 asociado al receptor T₃ (TRAC-1).^[2]

Función

NCOR2/SMRT es un corregulador transcripcional que contiene varios dominios moduladores de función incluyendo múltiples dominios de represión autónomos así como dos o tres dominios de interacción con receptores nucleares en el extremo C-terminal.^[1] NCOR2/SMRT actúa como un correpresor de la regulación de múltiples factores de transcripción. En este sentido, NCOR2/SMRT funciona como una plataforma proteica, facilitando el reclutamiento de histona deacetilasas hacia los promotores del ADN unidos a sus factores de transcripción.^[3]

Descubrimiento

NCOR2/SMRT fue clonado y caracterizado por primera vez en el laboratorio del Dr. Ronald M. Evans en el Salk Institute for Biological Studies.^[1] En otros estudios previos de esta proteína, se obtuvieron similares hallazgos en una variante referida como TRAC-1, que actualmente se denomina NCOR1.^[2]

Interacciones

La proteína NCOR2 ha demostrado ser capaz de interaccionar con:

• Receptor de hormona tiroidea beta^{[4] [5] [6]}
• Receptor de ácido retinoico alfa^{[7] [8]}
• HDAC1^{[9] [10]}
• Factor de crecimiento neural IB^[11]
• ZBTB16^{[12] [13] [8]}
• SIN3A^{[14] [15]}
• BCL6^{[16] [13] [17]}
• SNW1^{[18] [19]}
• Receptor androgénico^{[20] [21] [22]}
• PPAR delta^[23]
• c-Fos^[24]
• POU2F1^[25]
• HDAC5^[15]
• HDAC10^[9]
• RELA^{[26] [24]}
• RBPJ^{[27] [28]}
• TBL1X^{[29] [30] [14] [31]}
• RUNX1T1^{[12] [32]}
• HDAC4^{[33] [15]}
• Receptor de progesterona^[34]
• HDAC3^{[35] [29] [31] [33] [30] [14] [10]}
• SPEN^[36]
• Factor de respuesta al suero^[24]
• c-Jun^[24]
• Receptor de calcitriol^{[37] [5]}
• Proteína de la leucemia promielocítica^{[38] [39]}

Referencias

1. ↑ ^{a b c d} Chen JD, Evans RM (1995). «A transcriptional co-repressor that interacts with nuclear hormone receptors». Nature 377 (6548):  pp. 454–7. doi:10.1038/377454a0. PMID 7566127. 
2. ↑ ^{a b c} Sande S, Privalsky ML (1996). «Identification of TRACs (T3 receptor-associating cofactors), a family of cofactors that associate with, and modulate the activity of, nuclear hormone receptors». Mol Endocrinol 10 (7):  pp. 813–25. doi:10.1210/me.10.7.813. PMID 8813722. 
3. ↑ Nagy L, Kao HY, Chakravarti D, Lin RJ, Hassig CA, Ayer DE, Schreiber SL, Evans RM (1997). «Nuclear receptor repression mediated by a complex containing SMRT, mSin3A, and histone deacetylase». Cell 89 (3):  pp. 373–80. doi:10.1016/S0092-8674(00)80218-4. PMID 9150137. 
4. ↑ Liu, Y; Takeshita A, Misiti S, Chin W W, Yen P M (Oct. 1998). «Lack of coactivator interaction can be a mechanism for dominant negative activity by mutant thyroid hormone receptors». Endocrinology (UNITED STATES) 139 (10):  pp. 4197–204. ISSN 0013-7227. PMID 9751500. 
5. ↑ ^{a b} Tagami, T; Lutz W H, Kumar R, Jameson J L (Dec. 1998). «The interaction of the vitamin D receptor with nuclear receptor corepressors and coactivators». Biochem. Biophys. Res. Commun. (UNITED STATES) 253 (2):  pp. 358–63. doi:10.1006/bbrc.1998.9799. ISSN 0006-291X. PMID 9878542. 
6. ↑ Ando, S; Sarlis N J, Krishnan J, Feng X, Refetoff S, Zhang M Q, Oldfield E H, Yen P M (Sep. 2001). «Aberrant alternative splicing of thyroid hormone receptor in a TSH-secreting pituitary tumor is a mechanism for hormone resistance». Mol. Endocrinol. (United States) 15 (9):  pp. 1529–38. ISSN 0888-8809. PMID 11518802. 
7. ↑ Dong, Shuo; Tweardy David J (Apr. 2002). «Interactions of STAT5b-RARalpha, a novel acute promyelocytic leukemia fusion protein, with retinoic acid receptor and STAT3 signaling pathways». Blood (United States) 99 (8):  pp. 2637–46. ISSN 0006-4971. PMID 11929748. 
8. ↑ ^{a b} Hong, S H; David G, Wong C W, Dejean A, Privalsky M L (Aug. 1997). «SMRT corepressor interacts with PLZF and with the PML-retinoic acid receptor alpha (RARalpha) and PLZF-RARalpha oncoproteins associated with acute promyelocytic leukemia». Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 94 (17):  pp. 9028–33. ISSN 0027-8424. PMID 9256429. 
9. ↑ ^{a b} Fischer, Denise D; Cai Richard, Bhatia Umesh, Asselbergs Fred A M, Song Chuanzheng, Terry Robert, Trogani Nancy, Widmer Roland, Atadja Peter, Cohen Dalia (Feb. 2002). «Isolation and characterization of a novel class II histone deacetylase, HDAC10». J. Biol. Chem. (United States) 277 (8):  pp. 6656–66. doi:10.1074/jbc.M108055200. ISSN 0021-9258. PMID 11739383. 
10. ↑ ^{a b} Underhill, C; Qutob M S, Yee S P, Torchia J (Dec. 2000). «A novel nuclear receptor corepressor complex, N-CoR, contains components of the mammalian SWI/SNF complex and the corepressor KAP-1». J. Biol. Chem. (UNITED STATES) 275 (51):  pp. 40463–70. doi:10.1074/jbc.M007864200. ISSN 0021-9258. PMID 11013263. 
11. ↑ Sohn, Y C; Kwak E, Na Y, Lee J W, Lee S K (Nov. 2001). «Silencing mediator of retinoid and thyroid hormone receptors and activating signal cointegrator-2 as transcriptional coregulators of the orphan nuclear receptor Nur77». J. Biol. Chem. (United States) 276 (47):  pp. 43734–9. doi:10.1074/jbc.M107208200. ISSN 0021-9258. PMID 11559707. 
12. ↑ ^{a b} Takahashi, Shinichiro; McConnell Melanie J, Harigae Hideo, Kaku Mitsuo, Sasaki Takeshi, Melnick Ari M, Licht Jonathan D (Jun. 2004). «The Flt3 internal tandem duplication mutant inhibits the function of transcriptional repressors by blocking interactions with SMRT». Blood (United States) 103 (12):  pp. 4650–8. doi:10.1182/blood-2003-08-2759. ISSN 0006-4971. PMID 14982881. 
13. ↑ ^{a b} Wong, C W; Privalsky M L (Oct. 1998). «Components of the SMRT corepressor complex exhibit distinctive interactions with the POZ domain oncoproteins PLZF, PLZF-RARalpha, and BCL-6». J. Biol. Chem. (UNITED STATES) 273 (42):  pp. 27695–702. ISSN 0021-9258. PMID 9765306. 
14. ↑ ^{a b c} Li, J; Wang J, Wang J, Nawaz Z, Liu J M, Qin J, Wong J (Aug. 2000). «Both corepressor proteins SMRT and N-CoR exist in large protein complexes containing HDAC3». EMBO J. (ENGLAND) 19 (16):  pp. 4342–50. doi:10.1093/emboj/19.16.4342. ISSN 0261-4189. PMID 10944117. 
15. ↑ ^{a b c} Huang, E Y; Zhang J, Miska E A, Guenther M G, Kouzarides T, Lazar M A (Jan. 2000). «Nuclear receptor corepressors partner with class II histone deacetylases in a Sin3-independent repression pathway». Genes Dev. (UNITED STATES) 14 (1):  pp. 45–54. ISSN 0890-9369. PMID 10640275. 
16. ↑ Huynh, K D; Fischle W, Verdin E, Bardwell V J (Jul. 2000). «BCoR, a novel corepressor involved in BCL-6 repression». Genes Dev. (UNITED STATES) 14 (14):  pp. 1810–23. ISSN 0890-9369. PMID 10898795. 
17. ↑ Deltour, S; Guerardel C, Leprince D (Dec. 1999). «Recruitment of SMRT/N-CoR-mSin3A-HDAC-repressing complexes is not a general mechanism for BTB/POZ transcriptional repressors: the case of HIC-1 and gammaFBP-B». Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 96 (26):  pp. 14831–6. ISSN 0027-8424. PMID 10611298. 
18. ↑ Zhou, S; Fujimuro M, Hsieh J J, Chen L, Hayward S D (Feb. 2000). «A role for SKIP in EBNA2 activation of CBF1-repressed promoters». J. Virol. (UNITED STATES) 74 (4):  pp. 1939–47. ISSN 0022-538X. PMID 10644367. 
19. ↑ Zhou, S; Fujimuro M, Hsieh J J, Chen L, Miyamoto A, Weinmaster G, Hayward S D (Apr. 2000). «SKIP, a CBF1-associated protein, interacts with the ankyrin repeat domain of NotchIC To facilitate NotchIC function». Mol. Cell. Biol. (UNITED STATES) 20 (7):  pp. 2400–10. ISSN 0270-7306. PMID 10713164. 
20. ↑ Liao, Guoqing; Chen Liuh-Yow, Zhang Aihua, Godavarthy Aparna, Xia Fang, Ghosh Jagadish Chandra, Li Hui, Chen J Don (Feb. 2003). «Regulation of androgen receptor activity by the nuclear receptor corepressor SMRT». J. Biol. Chem. (United States) 278 (7):  pp. 5052–61. doi:10.1074/jbc.M206374200. ISSN 0021-9258. PMID 12441355. 
21. ↑ Song, Liang-Nian; Coghlan Meghan, Gelmann Edward P (Jan. 2004). «Antiandrogen effects of mifepristone on coactivator and corepressor interactions with the androgen receptor». Mol. Endocrinol. (United States) 18 (1):  pp. 70–85. doi:10.1210/me.2003-0189. ISSN 0888-8809. PMID 14593076. 
22. ↑ Dotzlaw, Helmut; Moehren Udo, Mink Sigrun, Cato Andrew C B, Iñiguez Lluhí Jorge A, Baniahmad Aria (Apr. 2002). «The amino terminus of the human AR is target for corepressor action and antihormone agonism». Mol. Endocrinol. (United States) 16 (4):  pp. 661–73. ISSN 0888-8809. PMID 11923464. 
23. ↑ Shi, Yanhong; Hon Michelle, Evans Ronald M (Mar. 2002). «The peroxisome proliferator-activated receptor delta, an integrator of transcriptional repression and nuclear receptor signaling». Proc. Natl. Acad. Sci. U.S.A. (United States) 99 (5):  pp. 2613–8. doi:10.1073/pnas.052707099. ISSN 0027-8424. PMID 11867749. 
24. ↑ ^{a b c d} Lee, S K; Kim J H, Lee Y C, Cheong J, Lee J W (Apr. 2000). «Silencing mediator of retinoic acid and thyroid hormone receptors, as a novel transcriptional corepressor molecule of activating protein-1, nuclear factor-kappaB, and serum response factor». J. Biol. Chem. (UNITED STATES) 275 (17):  pp. 12470–4. ISSN 0021-9258. PMID 10777532. 
25. ↑ Kakizawa, T; Miyamoto T, Ichikawa K, Takeda T, Suzuki S, Mori J, Kumagai M, Yamashita K, Hashizume K (Mar. 2001). «Silencing mediator for retinoid and thyroid hormone receptors interacts with octamer transcription factor-1 and acts as a transcriptional repressor». J. Biol. Chem. (United States) 276 (13):  pp. 9720–5. doi:10.1074/jbc.M008531200. ISSN 0021-9258. PMID 11134019. 
26. ↑ Espinosa, Lluís; Inglés-Esteve Julia, Robert-Moreno Alex, Bigas Anna (Feb. 2003). «IkappaBalpha and p65 regulate the cytoplasmic shuttling of nuclear corepressors: cross-talk between Notch and NFkappaB pathways». Mol. Biol. Cell (United States) 14 (2):  pp. 491–502. doi:10.1091/mbc.E02-07-0404. ISSN 1059-1524. PMID 12589049. 
27. ↑ Beatus, P; Lundkvist J, Oberg C, Pedersen K, Lendahl U (Jun. 2001). «The origin of the ankyrin repeat region in Notch intracellular domains is critical for regulation of HES promoter activity». Mech. Dev. (Ireland) 104 (1-2):  pp. 3–20. ISSN 0925-4773. PMID 11404076. 
28. ↑ Zhou, S; Hayward S D (Sep. 2001). «Nuclear localization of CBF1 is regulated by interactions with the SMRT corepressor complex». Mol. Cell. Biol. (United States) 21 (18):  pp. 6222–32. ISSN 0270-7306. PMID 11509665. 
29. ↑ ^{a b} Yoon, Ho-Geun; Chan Doug W, Huang Zhi-Qing, Li Jiwen, Fondell Joseph D, Qin Jun, Wong Jiemin (Mar. 2003). «Purification and functional characterization of the human N-CoR complex: the roles of HDAC3, TBL1 and TBLR1». EMBO J. (England) 22 (6):  pp. 1336–46. doi:10.1093/emboj/cdg120. ISSN 0261-4189. PMID 12628926. 
30. ↑ ^{a b} Guenther, Matthew G; Yu Jiujiu, Kao Gary D, Yen Tim J, Lazar Mitchell A (Dec. 2002). «Assembly of the SMRT-histone deacetylase 3 repression complex requires the TCP-1 ring complex». Genes Dev. (United States) 16 (24):  pp. 3130–5. doi:10.1101/gad.1037502. ISSN 0890-9369. PMID 12502735. 
31. ↑ ^{a b} Guenther, M G; Lane W S, Fischle W, Verdin E, Lazar M A, Shiekhattar R (May. 2000). «A core SMRT corepressor complex containing HDAC3 and TBL1, a WD40-repeat protein linked to deafness». Genes Dev. (UNITED STATES) 14 (9):  pp. 1048–57. ISSN 0890-9369. PMID 10809664. 
32. ↑ Zhang, J; Hug B A, Huang E Y, Chen C W, Gelmetti V, Maccarana M, Minucci S, Pelicci P G, Lazar M A (Jan. 2001). «Oligomerization of ETO is obligatory for corepressor interaction». Mol. Cell. Biol. (UNITED STATES) 21 (1):  pp. 156–63. doi:10.1128/MCB.21.1.156-163.2001. ISSN 0270-7306. PMID 11113190. 
33. ↑ ^{a b} Fischle, Wolfgang; Dequiedt Franck, Hendzel Michael J, Guenther Matthew G, Lazar Mitchell A, Voelter Wolfgang, Verdin Eric (Jan. 2002). «Enzymatic activity associated with class II HDACs is dependent on a multiprotein complex containing HDAC3 and SMRT/N-CoR». Mol. Cell (United States) 9 (1):  pp. 45–57. ISSN 1097-2765. PMID 11804585. 
34. ↑ Giangrande, P H; Kimbrel E A, Edwards D P, McDonnell D P (May. 2000). «The opposing transcriptional activities of the two isoforms of the human progesterone receptor are due to differential cofactor binding». Mol. Cell. Biol. (UNITED STATES) 20 (9):  pp. 3102–15. ISSN 0270-7306. PMID 10757795. 
35. ↑ Yoon, Ho-Geun; Chan Doug W, Reynolds Albert B, Qin Jun, Wong Jiemin (Sep. 2003). «N-CoR mediates DNA methylation-dependent repression through a methyl CpG binding protein Kaiso». Mol. Cell (United States) 12 (3):  pp. 723–34. ISSN 1097-2765. PMID 14527417. 
36. ↑ Shi, Y; Downes M, Xie W, Kao H Y, Ordentlich P, Tsai C C, Hon M, Evans R M (May. 2001). «Sharp, an inducible cofactor that integrates nuclear receptor repression and activation». Genes Dev. (United States) 15 (9):  pp. 1140–51. doi:10.1101/gad.871201. ISSN 0890-9369. PMID 11331609. 
37. ↑ Puccetti, Elena; Obradovic Darja, Beissert Tim, Bianchini Andrea, Washburn Birgit, Chiaradonna Ferdinando, Boehrer Simone, Hoelzer Dieter, Ottmann Oliver Gerhard, Pelicci Pier Giuseppe, Nervi Clara, Ruthardt Martin (Dec. 2002). «AML-associated translocation products block vitamin D(3)-induced differentiation by sequestering the vitamin D(3) receptor». Cancer Res. (United States) 62 (23):  pp. 7050–8. ISSN 0008-5472. PMID 12460926. 
38. ↑ Khan, M M; Nomura T, Kim H, Kaul S C, Wadhwa R, Shinagawa T, Ichikawa-Iwata E, Zhong S, Pandolfi P P, Ishii S (Jun. 2001). «Role of PML and PML-RARalpha in Mad-mediated transcriptional repression». Mol. Cell (United States) 7 (6):  pp. 1233–43. ISSN 1097-2765. PMID 11430826. 
39. ↑ Hong, S H; Yang Z, Privalsky M L (Nov. 2001). «Arsenic trioxide is a potent inhibitor of the interaction of SMRT corepressor with Its transcription factor partners, including the PML-retinoic acid receptor alpha oncoprotein found in human acute promyelocytic leukemia». Mol. Cell. Biol. (United States) 21 (21):  pp. 7172–82. doi:10.1128/MCB.21.21.7172-7182.2001. ISSN 0270-7306. PMID 11585900. 

Enlaces externos

• MeSH nuclear receptor corepressor 2