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Nuclear receptor co-repressor 2

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Template:PBB The nuclear receptor co-repressor 2 (NCOR2) is a transcriptional coregulatory protein which 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 which 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,[12][13][8] SIN3A,[14][15] BCL6,[16][13][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,[26][24] RBPJ,[27][28] TBL1X,[29][30][14][31] RUNX1T1,[12][32] HDAC4,[33][15] Progesterone receptor,[34] HDAC3,[35][29][31][33][30][14][10] SPEN,[36] Serum response factor,[24] C-jun,[24] Calcitriol receptor[37][5] 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  4. ^ Liu, Y (1998). "Lack of coactivator interaction can be a mechanism for dominant negative activity by mutant thyroid hormone receptors". Endocrinology. 139 (10). UNITED STATES: 4197–204. ISSN 0013-7227. PMID 9751500. {{cite journal}}: Check date values in: |year= (help); Cite has empty unknown parameters: |laydate=, |laysource=, and |laysummary= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help); Unknown parameter |quotes= ignored (help)CS1 maint: year (link)
  5. ^ a b Tagami, T (1998). "The interaction of the vitamin D receptor with nuclear receptor corepressors and coactivators". Biochem. Biophys. Res. Commun. 253 (2). UNITED STATES: 358–63. doi:10.1006/bbrc.1998.9799. ISSN 0006-291X. PMID 9878542. {{cite journal}}: Check date values in: |year= (help); Cite has empty unknown parameters: |laydate=, |laysource=, and |laysummary= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help); Unknown parameter |quotes= ignored (help)CS1 maint: year (link)
  6. ^ Ando, S (2001). "Aberrant alternative splicing of thyroid hormone receptor in a TSH-secreting pituitary tumor is a mechanism for hormone resistance". Mol. Endocrinol. 15 (9). United States: 1529–38. ISSN 0888-8809. PMID 11518802. {{cite journal}}: Check date values in: |year= (help); Cite has empty unknown parameters: |laydate=, |laysource=, and |laysummary= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help); Unknown parameter |quotes= ignored (help)CS1 maint: year (link)
  7. ^ Dong, Shuo (2002). "Interactions of STAT5b-RARalpha, a novel acute promyelocytic leukemia fusion protein, with retinoic acid receptor and STAT3 signaling pathways". Blood. 99 (8). United States: 2637–46. ISSN 0006-4971. PMID 11929748. {{cite journal}}: Check date values in: |year= (help); Cite has empty unknown parameters: |laydate=, |laysource=, and |laysummary= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help); Unknown parameter |quotes= ignored (help)CS1 maint: year (link)
  8. ^ a b Hong, S H (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. 94 (17). UNITED STATES: 9028–33. ISSN 0027-8424. PMID 9256429. {{cite journal}}: Check date values in: |year= (help); Cite has empty unknown parameters: |laydate=, |laysource=, and |laysummary= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help); Unknown parameter |quotes= ignored (help)CS1 maint: year (link)
  9. ^ a b Fischer, Denise D (2002). "Isolation and characterization of a novel class II histone deacetylase, HDAC10". J. Biol. Chem. 277 (8). United States: 6656–66. doi:10.1074/jbc.M108055200. ISSN 0021-9258. PMID 11739383. {{cite journal}}: Check date values in: |year= (help); Cite has empty unknown parameters: |laydate=, |laysource=, and |laysummary= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help); Unknown parameter |quotes= ignored (help)CS1 maint: unflagged free DOI (link) CS1 maint: year (link)
  10. ^ a b Underhill, C (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. 275 (51). UNITED STATES: 40463–70. doi:10.1074/jbc.M007864200. ISSN 0021-9258. PMID 11013263. {{cite journal}}: Check date values in: |year= (help); Cite has empty unknown parameters: |laydate=, |laysource=, and |laysummary= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help); Unknown parameter |quotes= ignored (help)CS1 maint: unflagged free DOI (link) CS1 maint: year (link)
  11. ^ Sohn, Y C (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. 276 (47). United States: 43734–9. doi:10.1074/jbc.M107208200. ISSN 0021-9258. PMID 11559707. {{cite journal}}: Check date values in: |year= (help); Cite has empty unknown parameters: |laydate=, |laysource=, and |laysummary= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help); Unknown parameter |quotes= ignored (help)CS1 maint: unflagged free DOI (link) CS1 maint: year (link)
  12. ^ a b Takahashi, Shinichiro (2004). "The Flt3 internal tandem duplication mutant inhibits the function of transcriptional repressors by blocking interactions with SMRT". Blood. 103 (12). United States: 4650–8. doi:10.1182/blood-2003-08-2759. ISSN 0006-4971. PMID 14982881. {{cite journal}}: Check date values in: |year= (help); Cite has empty unknown parameters: |laydate=, |laysource=, and |laysummary= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help); Unknown parameter |quotes= ignored (help)CS1 maint: year (link)
  13. ^ a b Wong, C W (1998). "Components of the SMRT corepressor complex exhibit distinctive interactions with the POZ domain oncoproteins PLZF, PLZF-RARalpha, and BCL-6". J. Biol. Chem. 273 (42). UNITED STATES: 27695–702. ISSN 0021-9258. PMID 9765306. {{cite journal}}: Check date values in: |year= (help); Cite has empty unknown parameters: |laydate=, |laysource=, and |laysummary= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help); Unknown parameter |quotes= ignored (help)CS1 maint: year (link)
  14. ^ a b c Li, J (2000). "Both corepressor proteins SMRT and N-CoR exist in large protein complexes containing HDAC3". EMBO J. 19 (16). ENGLAND: 4342–50. doi:10.1093/emboj/19.16.4342. ISSN 0261-4189. PMID 10944117. {{cite journal}}: Check date values in: |year= (help); Cite has empty unknown parameters: |laydate=, |laysource=, and |laysummary= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help); Unknown parameter |quotes= ignored (help)CS1 maint: year (link)
  15. ^ a b c Huang, E Y (2000). "Nuclear receptor corepressors partner with class II histone deacetylases in a Sin3-independent repression pathway". Genes Dev. 14 (1). UNITED STATES: 45–54. ISSN 0890-9369. PMID 10640275. {{cite journal}}: Check date values in: |year= (help); Cite has empty unknown parameters: |laydate=, |laysource=, and |laysummary= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help); Unknown parameter |quotes= ignored (help)CS1 maint: year (link)
  16. ^ Huynh, K D (2000). "BCoR, a novel corepressor involved in BCL-6 repression". Genes Dev. 14 (14). UNITED STATES: 1810–23. ISSN 0890-9369. PMID 10898795. {{cite journal}}: Check date values in: |year= (help); Cite has empty unknown parameters: |laydate=, |laysource=, and |laysummary= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help); Unknown parameter |quotes= ignored (help)CS1 maint: year (link)
  17. ^ Deltour, S (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. 96 (26). UNITED STATES: 14831–6. ISSN 0027-8424. PMID 10611298. {{cite journal}}: Check date values in: |year= (help); Cite has empty unknown parameters: |laydate=, |laysource=, and |laysummary= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help); Unknown parameter |quotes= ignored (help)CS1 maint: year (link)
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  19. ^ Zhou, S (2000). "SKIP, a CBF1-associated protein, interacts with the ankyrin repeat domain of NotchIC To facilitate NotchIC function". Mol. Cell. Biol. 20 (7). UNITED STATES: 2400–10. ISSN 0270-7306. PMID 10713164. {{cite journal}}: Check date values in: |year= (help); Cite has empty unknown parameters: |laydate=, |laysource=, and |laysummary= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help); Unknown parameter |quotes= ignored (help)CS1 maint: year (link)
  20. ^ Liao, Guoqing (2003). "Regulation of androgen receptor activity by the nuclear receptor corepressor SMRT". J. Biol. Chem. 278 (7). United States: 5052–61. doi:10.1074/jbc.M206374200. ISSN 0021-9258. PMID 12441355. {{cite journal}}: Check date values in: |year= (help); Cite has empty unknown parameters: |laydate=, |laysource=, and |laysummary= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help); Unknown parameter |quotes= ignored (help)CS1 maint: unflagged free DOI (link) CS1 maint: year (link)
  21. ^ Song, Liang-Nian (2004). "Antiandrogen effects of mifepristone on coactivator and corepressor interactions with the androgen receptor". Mol. Endocrinol. 18 (1). United States: 70–85. doi:10.1210/me.2003-0189. ISSN 0888-8809. PMID 14593076. {{cite journal}}: Check date values in: |year= (help); Cite has empty unknown parameters: |laydate=, |laysource=, and |laysummary= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help); Unknown parameter |quotes= ignored (help)CS1 maint: year (link)
  22. ^ Dotzlaw, Helmut (2002). "The amino terminus of the human AR is target for corepressor action and antihormone agonism". Mol. Endocrinol. 16 (4). United States: 661–73. ISSN 0888-8809. PMID 11923464. {{cite journal}}: Check date values in: |year= (help); Cite has empty unknown parameters: |laydate=, |laysource=, and |laysummary= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help); Unknown parameter |quotes= ignored (help)CS1 maint: year (link)
  23. ^ Shi, Yanhong (2002). "The peroxisome proliferator-activated receptor delta, an integrator of transcriptional repression and nuclear receptor signaling". Proc. Natl. Acad. Sci. U.S.A. 99 (5). United States: 2613–8. doi:10.1073/pnas.052707099. ISSN 0027-8424. PMID 11867749. {{cite journal}}: Check date values in: |year= (help); Cite has empty unknown parameters: |laydate=, |laysource=, and |laysummary= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help); Unknown parameter |quotes= ignored (help)CS1 maint: year (link)
  24. ^ a b c d Lee, S K (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. 275 (17). UNITED STATES: 12470–4. ISSN 0021-9258. PMID 10777532. {{cite journal}}: Check date values in: |year= (help); Cite has empty unknown parameters: |laydate=, |laysource=, and |laysummary= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help); Unknown parameter |quotes= ignored (help)CS1 maint: year (link)
  25. ^ Kakizawa, T (2001). "Silencing mediator for retinoid and thyroid hormone receptors interacts with octamer transcription factor-1 and acts as a transcriptional repressor". J. Biol. Chem. 276 (13). United States: 9720–5. doi:10.1074/jbc.M008531200. ISSN 0021-9258. PMID 11134019. {{cite journal}}: Check date values in: |year= (help); Cite has empty unknown parameters: |laydate=, |laysource=, and |laysummary= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help); Unknown parameter |quotes= ignored (help)CS1 maint: unflagged free DOI (link) CS1 maint: year (link)
  26. ^ Espinosa, Lluís (2003). "IkappaBalpha and p65 regulate the cytoplasmic shuttling of nuclear corepressors: cross-talk between Notch and NFkappaB pathways". Mol. Biol. Cell. 14 (2). United States: 491–502. doi:10.1091/mbc.E02-07-0404. ISSN 1059-1524. PMID 12589049. {{cite journal}}: Check date values in: |year= (help); Cite has empty unknown parameters: |laydate=, |laysource=, and |laysummary= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help); Unknown parameter |quotes= ignored (help)CS1 maint: year (link)
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  37. ^ Puccetti, Elena (2002). "AML-associated translocation products block vitamin D(3)-induced differentiation by sequestering the vitamin D(3) receptor". Cancer Res. 62 (23). United States: 7050–8. ISSN 0008-5472. PMID 12460926. {{cite journal}}: Check date values in: |year= (help); Cite has empty unknown parameters: |laydate=, |laysource=, and |laysummary= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help); Unknown parameter |quotes= ignored (help)CS1 maint: year (link)
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  39. ^ Hong, S H (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. 21 (21). United States: 7172–82. doi:10.1128/MCB.21.21.7172-7182.2001. ISSN 0270-7306. PMID 11585900. {{cite journal}}: Check date values in: |year= (help); Cite has empty unknown parameters: |laydate=, |laysource=, and |laysummary= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help); Unknown parameter |quotes= ignored (help)CS1 maint: year (link)

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