Template:PBB 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]
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,[4][5][6]
- BCL6,[7][8][9]
- C-Fos,[10]
- C-jun,[10]
- HDAC1,[11][12]
- HDAC3,[12][13][14][15][16][17][18]
- HDAC4,[19][17]
- HDAC5,[19]
- HDAC10,[11]
- MeCP2,[20]
- NR4A1,[21]
- POU2F1,[22]
- PPARD,[23]
- PGR,[24]
- PML[25][26]
- RBPJ,[27][28]
- RELA,[10][29]
- RUNX1T1,[30][31]
- RARA,[32][33]
- SIN3A,[13][19]
- SNW1,[34][35]
- SPEN,[36]
- SRF,[10]
- TBL1X,[13][14][15][16]
- THRB,[37][38][39]
- VDR,[38][40] and
- ZBTB16.[33][30][7]
References
- ^ 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.
- ^ 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.
- ^ 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) - ^ Liao G, Chen LY, Zhang A, Godavarthy A, Xia F, Ghosh JC, Li H, Chen JD (2003). "Regulation of androgen receptor activity by the nuclear receptor corepressor SMRT". J. Biol. Chem. 278 (7): 5052–61. doi:10.1074/jbc.M206374200. PMID 12441355.
{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - ^ Song LN, Coghlan M, Gelmann EP (2004). "Antiandrogen effects of mifepristone on coactivator and corepressor interactions with the androgen receptor". Mol. Endocrinol. 18 (1): 70–85. doi:10.1210/me.2003-0189. PMID 14593076.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Dotzlaw H, Moehren U, Mink S, Cato AC, Iñiguez Lluhí JA, Baniahmad A (2002). "The amino terminus of the human AR is target for corepressor action and antihormone agonism". Mol. Endocrinol. 16 (4): 661–73. PMID 11923464.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ a b Wong CW, Privalsky ML (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): 27695–702. PMID 9765306.
- ^ Huynh KD, Fischle W, Verdin E, Bardwell VJ (2000). "BCoR, a novel corepressor involved in BCL-6 repression". Genes Dev. 14 (14): 1810–23. PMC 316791. PMID 10898795.
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Further reading
External links
- nuclear receptor corepressor 2 at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- NURSA C98