Nuclear receptor co-repressor 2

Nuclear receptor corepressor 2

PDB rendering based on 1xc5.
Identifiers
Symbols NCOR2; CTG26; FLJ25011; N-CoR2; SMAP270; SMRT; SMRTE; SMRTE-tau; TNRC14; TRAC; TRAC-1; TRAC1
External IDs OMIM: 600848 MGI: 1337080 HomoloGene: 31370 GeneCards: NCOR2 Gene
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez 9612 20602
Ensembl ENSG00000196498 ENSMUSG00000029478
UniProt Q9Y618 n/a
RefSeq (mRNA) NM_001077261.3 NM_011424.2
RefSeq (protein) NP_001070729.2 NP_035554.2
Location (UCSC) Chr 12:
124.81 – 125.05 Mb		 Chr 5:
125.5 – 125.66 Mb
PubMed search [1] [2]

The nuclear receptor co-repressor 2 (NCOR2) is a transcriptional coregulatory protein that contains several nuclear receptor-interacting domains. In addition, NCOR2 appears to recruit histone deacetylases to DNA promoter regions. Hence NCOR2 assists nuclear receptors in the down regulation of target gene expression.[1][2] NCOR2 is also referred to as a silencing mediator for retinoid or thyroid-hormone receptors (SMRT)[1] or T3 receptor-associating cofactor 1 (TRAC-1).[2]

Contents

Function

NCOR2/SMRT is a transcriptional coregulatory protein that contains several modulatory functional domains including multiple autonomous repression domains as well as two or three C-terminal nuclear receptor-interacting domains.[1] NCOR2/SMRT serves as a repressive coregulatory factor (corepressor) for multiple transcription factor pathways. In this regard, NCOR2/SMRT functions as a platform protein, facilitating the recruitment of histone deacetylases to the DNA promoters bound by its interacting transcription factors.[3]

Discovery

SMRT was initially cloned and characterized in the laboratory of Dr. Ronald M. Evans at the Salk Institute for Biological Studies.[1] In another early investigation into this molecule, similar findings were reported in a variant referred to as TRAC-1.[2]

Interactions

Nuclear receptor co-repressor 2 has been shown to interact with Thyroid hormone receptor beta,[4][5][6] Retinoic acid receptor alpha,[7][8] HDAC1,[9][10] Nerve Growth factor IB,[11] Zinc finger and BTB domain-containing protein 16,[8][12][13] SIN3A,[14][15] BCL6,[13][16][17] SNW1,[18][19] Androgen receptor,[20][21][22] Peroxisome proliferator-activated receptor delta,[23] C-Fos,[24] POU2F1,[25] Histone deacetylase 5,[15] HDAC10,[9] RELA,[24][26] RBPJ,[27][28] TBL1X,[14][29][30][31] RUNX1T1,[12][32] HDAC4,[15][33] Progesterone receptor,[34] HDAC3,[10][14][29][30][31][33][35] SPEN,[36] Serum response factor,[24] C-jun,[24] Calcitriol receptor[5][37] and Promyelocytic leukemia protein.[38][39]

References

  1. ^ a b c d Chen JD, Evans RM (1995). "A transcriptional co-repressor that interacts with nuclear hormone receptors". Nature 377 (6548): 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): 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): 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): 4197–204. doi:10.1210/en.139.10.4197. 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): 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): 1529–38. doi:10.1210/me.15.9.1529. 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): 2637–46. doi:10.1182/blood.V99.8.2637. 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 α (RARα) and PLZF-RARα oncoproteins associated with acute promyelocytic leukemia". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 94 (17): 9028–33. doi:10.1073/pnas.94.17.9028. ISSN 0027-8424. PMC 23013. PMID 9256429. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=23013. 
  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): 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): 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): 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): 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): 27695–702. doi:10.1074/jbc.273.42.27695. 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): 4342–50. doi:10.1093/emboj/19.16.4342. ISSN 0261-4189. PMC 302030. PMID 10944117. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=302030. 
  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): 45–54. ISSN 0890-9369. PMC 316335. PMID 10640275. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=316335. 
  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): 1810–23. doi:10.1101/gad.14.14.1810. ISSN 0890-9369. PMC 316791. PMID 10898795. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=316791. 
  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 γFBP-B". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 96 (26): 14831–6. doi:10.1073/pnas.96.26.14831. ISSN 0027-8424. PMC 24733. PMID 10611298. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=24733. 
  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): 1939–47. doi:10.1128/JVI.74.4.1939-1947.2000. ISSN 0022-538X. PMC 111672. PMID 10644367. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=111672. 
  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): 2400–10. doi:10.1128/MCB.20.7.2400-2410.2000. ISSN 0270-7306. PMC 85419. PMID 10713164. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=85419. 
  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): 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): 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): 661–73. doi:10.1210/me.16.4.661. ISSN 0888-8809. PMID 11923464. 
  23. ^ Shi, Yanhong; Hon Michelle, Evans Ronald M (Mar. 2002). "The peroxisome proliferator-activated receptor δ, an integrator of transcriptional repression and nuclear receptor signaling". Proc. Natl. Acad. Sci. U.S.A. (United States) 99 (5): 2613–8. doi:10.1073/pnas.052707099. ISSN 0027-8424. PMC 122396. PMID 11867749. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=122396. 
  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): 12470–4. doi:10.1074/jbc.275.17.12470. 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): 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). "IκBα and p65 Regulate the Cytoplasmic Shuttling of Nuclear Corepressors: Cross-talk between Notch and NFκB Pathways". Mol. Biol. Cell (United States) 14 (2): 491–502. doi:10.1091/mbc.E02-07-0404. ISSN 1059-1524. PMC 149987. PMID 12589049. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=149987. 
  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): 3–20. doi:10.1016/S0925-4773(01)00373-2. 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): 6222–32. doi:10.1128/MCB.21.18.6222-6232.2001. ISSN 0270-7306. PMC 87339. PMID 11509665. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=87339. 
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  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 α Oncoprotein Found in Human Acute Promyelocytic Leukemia". Mol. Cell. Biol. (United States) 21 (21): 7172–82. doi:10.1128/MCB.21.21.7172-7182.2001. ISSN 0270-7306. PMC 99892. PMID 11585900. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=99892. 

Further reading

Coactivators
ARA (54, 55, 70) • BCAS3 • CARM1 • p300-CBP (EP300, CREBBP) • CRTC (1, 2, 3) • DRIP/TRAP • 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
see also transcription factor/coregulator deficiencies
B bsyn: dna (repl, cycl, reco, repr) · tscr (fact, tcrg, nucl, rnat, rept, ptts) · tltn (risu, pttl, nexn) · dnab, rnab/runp · stru (domn, 1°, 2°, 3°, 4°)

External links