Biology:Nuclear receptor co-repressor 2
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Short description: Protein-coding gene in the species Homo sapiens
 Generic protein structure example |
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]
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]
Family
It is a member of the family of nuclear receptor corepressors; the other human protein that is a member of that family is Nuclear receptor co-repressor 1.[4]
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:
- AR,[5][6][7]
- BCL6,[8][9][10]
- C-Fos,[11]
- C-jun,[11]
- HDAC1,[12][13]
- HDAC3,[13][14][15][16][17][18][19]
- HDAC4,[18][20]
- HDAC5,[20]
- HDAC10,[12]
- MeCP2,[21]
- NR4A1,[22]
- POU2F1,[23]
- PPARD,[24]
- PGR,[25]
- PML[26][27]
- RBPJ,[28][29]
- RELA,[11][30]
- RUNX1T1,[31][32]
- RARA,[33][34]
- SIN3A,[14][20]
- SNW1,[35][36]
- SPEN,[37]
- SRF,[11]
- TBL1X,[14][15][16][17]
- THRB,[38][39][40]
- VDR,[39][41] and
- ZBTB16.[8][31][34]
References
- ↑ 1.0 1.1 1.2 1.3 "A transcriptional co-repressor that interacts with nuclear hormone receptors". Nature 377 (6548): 454–7. October 1995. doi:10.1038/377454a0. PMID 7566127. Bibcode: 1995Natur.377..454C.
- ↑ 2.0 2.1 2.2 "Identification of TRACs (T3 receptor-associating cofactors), a family of cofactors that associate with, and modulate the activity of, nuclear hormone receptors". Molecular Endocrinology 10 (7): 813–25. July 1996. doi:10.1210/mend.10.7.8813722. PMID 8813722.
- ↑ "Nuclear receptor repression mediated by a complex containing SMRT, mSin3A, and histone deacetylase". Cell 89 (3): 373–80. May 1997. doi:10.1016/S0092-8674(00)80218-4. PMID 9150137.
- ↑ UniProt Nuclear receptor corepressors family Page accessed June 26, 2016
- ↑ "Regulation of androgen receptor activity by the nuclear receptor corepressor SMRT". The Journal of Biological Chemistry 278 (7): 5052–61. February 2003. doi:10.1074/jbc.M206374200. PMID 12441355.
- ↑ "Antiandrogen effects of mifepristone on coactivator and corepressor interactions with the androgen receptor". Molecular Endocrinology 18 (1): 70–85. January 2004. doi:10.1210/me.2003-0189. PMID 14593076.
- ↑ "The amino terminus of the human AR is target for corepressor action and antihormone agonism". Molecular Endocrinology 16 (4): 661–73. April 2002. doi:10.1210/me.16.4.661. PMID 11923464.
- ↑ 8.0 8.1 "Components of the SMRT corepressor complex exhibit distinctive interactions with the POZ domain oncoproteins PLZF, PLZF-RARalpha, and BCL-6". The Journal of Biological Chemistry 273 (42): 27695–702. October 1998. doi:10.1074/jbc.273.42.27695. PMID 9765306.
- ↑ "BCoR, a novel corepressor involved in BCL-6 repression". Genes & Development 14 (14): 1810–23. July 2000. doi:10.1101/gad.14.14.1810. PMID 10898795.
- ↑ "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". Proceedings of the National Academy of Sciences of the United States of America 96 (26): 14831–6. December 1999. doi:10.1073/pnas.96.26.14831. PMID 10611298. Bibcode: 1999PNAS...9614831D.
- ↑ 11.0 11.1 11.2 11.3 "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". The Journal of Biological Chemistry 275 (17): 12470–4. April 2000. doi:10.1074/jbc.275.17.12470. PMID 10777532.
- ↑ 12.0 12.1 "Isolation and characterization of a novel class II histone deacetylase, HDAC10". The Journal of Biological Chemistry 277 (8): 6656–66. February 2002. doi:10.1074/jbc.M108055200. PMID 11739383.
- ↑ 13.0 13.1 "A novel nuclear receptor corepressor complex, N-CoR, contains components of the mammalian SWI/SNF complex and the corepressor KAP-1". The Journal of Biological Chemistry 275 (51): 40463–70. December 2000. doi:10.1074/jbc.M007864200. PMID 11013263.
- ↑ 14.0 14.1 14.2 "Both corepressor proteins SMRT and N-CoR exist in large protein complexes containing HDAC3". The EMBO Journal 19 (16): 4342–50. August 2000. doi:10.1093/emboj/19.16.4342. PMID 10944117.
- ↑ 15.0 15.1 "Purification and functional characterization of the human N-CoR complex: the roles of HDAC3, TBL1 and TBLR1". The EMBO Journal 22 (6): 1336–46. March 2003. doi:10.1093/emboj/cdg120. PMID 12628926.
- ↑ 16.0 16.1 "Assembly of the SMRT-histone deacetylase 3 repression complex requires the TCP-1 ring complex". Genes & Development 16 (24): 3130–5. December 2002. doi:10.1101/gad.1037502. PMID 12502735.
- ↑ 17.0 17.1 "A core SMRT corepressor complex containing HDAC3 and TBL1, a WD40-repeat protein linked to deafness". Genes & Development 14 (9): 1048–57. May 2000. doi:10.1101/gad.14.9.1048. PMID 10809664.
- ↑ 18.0 18.1 "Enzymatic activity associated with class II HDACs is dependent on a multiprotein complex containing HDAC3 and SMRT/N-CoR". Molecular Cell 9 (1): 45–57. January 2002. doi:10.1016/S1097-2765(01)00429-4. PMID 11804585.
- ↑ "N-CoR mediates DNA methylation-dependent repression through a methyl CpG binding protein Kaiso". Molecular Cell 12 (3): 723–34. September 2003. doi:10.1016/j.molcel.2003.08.008. PMID 14527417.
- ↑ 20.0 20.1 20.2 "Nuclear receptor corepressors partner with class II histone deacetylases in a Sin3-independent repression pathway". Genes & Development 14 (1): 45–54. January 2000. doi:10.1101/gad.14.1.45. PMID 10640275.
- ↑ "Rett syndrome mutations abolish the interaction of MeCP2 with the NCoR/SMRT co-repressor". Nature Neuroscience 16 (7): 898–902. July 2013. doi:10.1038/nn.3434. PMID 23770565.
- ↑ "Silencing mediator of retinoid and thyroid hormone receptors and activating signal cointegrator-2 as transcriptional coregulators of the orphan nuclear receptor Nur77". The Journal of Biological Chemistry 276 (47): 43734–9. November 2001. doi:10.1074/jbc.M107208200. PMID 11559707.
- ↑ "Silencing mediator for retinoid and thyroid hormone receptors interacts with octamer transcription factor-1 and acts as a transcriptional repressor". The Journal of Biological Chemistry 276 (13): 9720–5. March 2001. doi:10.1074/jbc.M008531200. PMID 11134019.
- ↑ "The peroxisome proliferator-activated receptor delta, an integrator of transcriptional repression and nuclear receptor signaling". Proceedings of the National Academy of Sciences of the United States of America 99 (5): 2613–8. March 2002. doi:10.1073/pnas.052707099. PMID 11867749. Bibcode: 2002PNAS...99.2613S.
- ↑ "The opposing transcriptional activities of the two isoforms of the human progesterone receptor are due to differential cofactor binding". Molecular and Cellular Biology 20 (9): 3102–15. May 2000. doi:10.1128/MCB.20.9.3102-3115.2000. PMID 10757795.
- ↑ "Role of PML and PML-RARalpha in Mad-mediated transcriptional repression". Molecular Cell 7 (6): 1233–43. June 2001. doi:10.1016/S1097-2765(01)00257-X. PMID 11430826.
- ↑ "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". Molecular and Cellular Biology 21 (21): 7172–82. November 2001. doi:10.1128/MCB.21.21.7172-7182.2001. PMID 11585900.
- ↑ "The origin of the ankyrin repeat region in Notch intracellular domains is critical for regulation of HES promoter activity". Mechanisms of Development 104 (1–2): 3–20. June 2001. doi:10.1016/S0925-4773(01)00373-2. PMID 11404076.
- ↑ "Nuclear localization of CBF1 is regulated by interactions with the SMRT corepressor complex". Molecular and Cellular Biology 21 (18): 6222–32. September 2001. doi:10.1128/MCB.21.18.6222-6232.2001. PMID 11509665.
- ↑ "IkappaBalpha and p65 regulate the cytoplasmic shuttling of nuclear corepressors: cross-talk between Notch and NFkappaB pathways". Molecular Biology of the Cell 14 (2): 491–502. February 2003. doi:10.1091/mbc.E02-07-0404. PMID 12589049.
- ↑ 31.0 31.1 "The Flt3 internal tandem duplication mutant inhibits the function of transcriptional repressors by blocking interactions with SMRT". Blood 103 (12): 4650–8. June 2004. doi:10.1182/blood-2003-08-2759. PMID 14982881.
- ↑ "Oligomerization of ETO is obligatory for corepressor interaction". Molecular and Cellular Biology 21 (1): 156–63. January 2001. doi:10.1128/MCB.21.1.156-163.2001. PMID 11113190.
- ↑ "Interactions of STAT5b-RARalpha, a novel acute promyelocytic leukemia fusion protein, with retinoic acid receptor and STAT3 signaling pathways". Blood 99 (8): 2637–46. April 2002. doi:10.1182/blood.V99.8.2637. PMID 11929748.
- ↑ 34.0 34.1 "SMRT corepressor interacts with PLZF and with the PML-retinoic acid receptor alpha (RARalpha) and PLZF-RARalpha oncoproteins associated with acute promyelocytic leukemia". Proceedings of the National Academy of Sciences of the United States of America 94 (17): 9028–33. August 1997. doi:10.1073/pnas.94.17.9028. PMID 9256429. Bibcode: 1997PNAS...94.9028H.
- ↑ "A role for SKIP in EBNA2 activation of CBF1-repressed promoters". Journal of Virology 74 (4): 1939–47. February 2000. doi:10.1128/JVI.74.4.1939-1947.2000. PMID 10644367.
- ↑ "SKIP, a CBF1-associated protein, interacts with the ankyrin repeat domain of NotchIC To facilitate NotchIC function". Molecular and Cellular Biology 20 (7): 2400–10. April 2000. doi:10.1128/MCB.20.7.2400-2410.2000. PMID 10713164.
- ↑ "Sharp, an inducible cofactor that integrates nuclear receptor repression and activation". Genes & Development 15 (9): 1140–51. May 2001. doi:10.1101/gad.871201. PMID 11331609.
- ↑ "Lack of coactivator interaction can be a mechanism for dominant negative activity by mutant thyroid hormone receptors". Endocrinology 139 (10): 4197–204. October 1998. doi:10.1210/endo.139.10.6218. PMID 9751500.
- ↑ 39.0 39.1 "The interaction of the vitamin D receptor with nuclear receptor corepressors and coactivators". Biochemical and Biophysical Research Communications 253 (2): 358–63. December 1998. doi:10.1006/bbrc.1998.9799. PMID 9878542.
- ↑ "Aberrant alternative splicing of thyroid hormone receptor in a TSH-secreting pituitary tumor is a mechanism for hormone resistance". Molecular Endocrinology 15 (9): 1529–38. September 2001. doi:10.1210/mend.15.9.0687. PMID 11518802.
- ↑ "AML-associated translocation products block vitamin D(3)-induced differentiation by sequestering the vitamin D(3) receptor". Cancer Research 62 (23): 7050–8. December 2002. PMID 12460926.
Further reading
- "Ligand-independent repression by the thyroid hormone receptor mediated by a nuclear receptor co-repressor". Nature 377 (6548): 397–404. October 1995. doi:10.1038/377397a0. PMID 7566114. Bibcode: 1995Natur.377..397H.
- "A transcriptional co-repressor that interacts with nuclear hormone receptors". Nature 377 (6548): 454–7. October 1995. doi:10.1038/377454a0. PMID 7566127. Bibcode: 1995Natur.377..454C.
- "Identification of TRACs (T3 receptor-associating cofactors), a family of cofactors that associate with, and modulate the activity of, nuclear hormone receptors". Molecular Endocrinology 10 (7): 813–25. July 1996. doi:10.1210/mend.10.7.8813722. PMID 8813722.
- "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Research 6 (9): 791–806. September 1996. doi:10.1101/gr.6.9.791. PMID 8889548.
- "cDNAs with long CAG trinucleotide repeats from human brain". Human Genetics 100 (1): 114–22. July 1997. doi:10.1007/s004390050476. PMID 9225980.
- "SMRT corepressor interacts with PLZF and with the PML-retinoic acid receptor alpha (RARalpha) and PLZF-RARalpha oncoproteins associated with acute promyelocytic leukemia". Proceedings of the National Academy of Sciences of the United States of America 94 (17): 9028–33. August 1997. doi:10.1073/pnas.94.17.9028. PMID 9256429. Bibcode: 1997PNAS...94.9028H.
- "Nuclear receptor coactivator ACTR is a novel histone acetyltransferase and forms a multimeric activation complex with P/CAF and CBP/p300". Cell 90 (3): 569–80. August 1997. doi:10.1016/S0092-8674(00)80516-4. PMID 9267036.
- "Role of the histone deacetylase complex in acute promyelocytic leukaemia". Nature 391 (6669): 811–4. February 1998. doi:10.1038/35895. PMID 9486654. Bibcode: 1998Natur.391..811L.
- "SAP30, a component of the mSin3 corepressor complex involved in N-CoR-mediated repression by specific transcription factors". Molecular Cell 2 (1): 33–42. July 1998. doi:10.1016/S1097-2765(00)80111-2. PMID 9702189.
- "Lack of coactivator interaction can be a mechanism for dominant negative activity by mutant thyroid hormone receptors". Endocrinology 139 (10): 4197–204. October 1998. doi:10.1210/endo.139.10.6218. PMID 9751500.
- "Components of the SMRT corepressor complex exhibit distinctive interactions with the POZ domain oncoproteins PLZF, PLZF-RARalpha, and BCL-6". The Journal of Biological Chemistry 273 (42): 27695–702. October 1998. doi:10.1074/jbc.273.42.27695. PMID 9765306.
- "Unique forms of human and mouse nuclear receptor corepressor SMRT". Proceedings of the National Academy of Sciences of the United States of America 96 (6): 2639–44. March 1999. doi:10.1073/pnas.96.6.2639. PMID 10077563. Bibcode: 1999PNAS...96.2639O.
- "SMRTe, a silencing mediator for retinoid and thyroid hormone receptors-extended isoform that is more related to the nuclear receptor corepressor". Proceedings of the National Academy of Sciences of the United States of America 96 (7): 3519–24. March 1999. doi:10.1073/pnas.96.7.3519. PMID 10097068. Bibcode: 1999PNAS...96.3519P.
- "Interactions of nuclear receptor coactivator/corepressor proteins with the aryl hydrocarbon receptor complex". Archives of Biochemistry and Biophysics 367 (2): 250–7. July 1999. doi:10.1006/abbi.1999.1282. PMID 10395741.
- "The nuclear receptor corepressor N-CoR regulates differentiation: N-CoR directly interacts with MyoD". Molecular Endocrinology 13 (7): 1155–68. July 1999. doi:10.1210/mend.13.7.0305. PMID 10406466.
- "Isolation of a novel histone deacetylase reveals that class I and class II deacetylases promote SMRT-mediated repression". Genes & Development 14 (1): 55–66. January 2000. doi:10.1101/gad.14.1.55. PMID 10640276.
- "SKIP, a CBF1-associated protein, interacts with the ankyrin repeat domain of NotchIC To facilitate NotchIC function". Molecular and Cellular Biology 20 (7): 2400–10. April 2000. doi:10.1128/MCB.20.7.2400-2410.2000. PMID 10713164.
- "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". The Journal of Biological Chemistry 275 (17): 12470–4. April 2000. doi:10.1074/jbc.275.17.12470. PMID 10777532.
- "A core SMRT corepressor complex containing HDAC3 and TBL1, a WD40-repeat protein linked to deafness". Genes & Development 14 (9): 1048–57. May 2000. doi:10.1101/gad.14.9.1048. PMID 10809664.
- "Regulation of histone deacetylase 4 and 5 and transcriptional activity by 14-3-3-dependent cellular localization". Proceedings of the National Academy of Sciences of the United States of America 97 (14): 7835–40. July 2000. doi:10.1073/pnas.140199597. PMID 10869435. Bibcode: 2000PNAS...97.7835G.
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External links
- nuclear receptor corepressor 2 at the US National Library of Medicine Medical Subject Headings (MeSH)
- NURSA C98
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