Nuclear receptor co-repressor 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. 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.

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.

Discovery

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

Interactions

Nuclear receptor co-repressor 2 has been shown to interact with:

• AR
• BCL6
• C-Fos
• C-jun
• HDAC1
• HDAC3
• HDAC4
• HDAC5
• HDAC10
• MeCP2
• NR4A1
• POU2F1
• PPARD
• PGR
• PML
• RBPJ
• RELA
• RUNX1T1
• RARA
• SIN3A
• SNW1
• SPEN
• SRF
• TBL1X
• THRB
• VDR
• ZBTB16

References

References

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2. (July 1996). "Identification of TRACs (T3 receptor-associating cofactors), a family of cofactors that associate with, and modulate the activity of, nuclear hormone receptors". Molecular Endocrinology.
3. (May 1997). "Nuclear receptor repression mediated by a complex containing SMRT, mSin3A, and histone deacetylase". Cell.
4. UniProt [https://www.uniprot.org/uniprot/?query=family:%22N-CoR+nuclear+receptor+corepressors+family%22 Nuclear receptor corepressors family] Page accessed June 26, 2016
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8. (July 2000). "BCoR, a novel corepressor involved in BCL-6 repression". Genes & Development.
9. (December 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". Proceedings of the National Academy of Sciences of the United States of America.
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13. (September 2003). "N-CoR mediates DNA methylation-dependent repression through a methyl CpG binding protein Kaiso". Molecular Cell.
14. (January 2002). "Enzymatic activity associated with class II HDACs is dependent on a multiprotein complex containing HDAC3 and SMRT/N-CoR". Molecular Cell.
15. (July 2013). "Rett syndrome mutations abolish the interaction of MeCP2 with the NCoR/SMRT co-repressor". Nature Neuroscience.
16. (November 2001). "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.
17. (March 2001). "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.
18. (March 2002). "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.
19. (May 2000). "The opposing transcriptional activities of the two isoforms of the human progesterone receptor are due to differential cofactor binding". Molecular and Cellular Biology.
20. (June 2001). "Role of PML and PML-RARalpha in Mad-mediated transcriptional repression". Molecular Cell.
21. (November 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". Molecular and Cellular Biology.
22. (June 2001). "The origin of the ankyrin repeat region in Notch intracellular domains is critical for regulation of HES promoter activity". Mechanisms of Development.
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24. (February 2003). "IkappaBalpha and p65 regulate the cytoplasmic shuttling of nuclear corepressors: cross-talk between Notch and NFkappaB pathways". Molecular Biology of the Cell.
25. (January 2001). "Oligomerization of ETO is obligatory for corepressor interaction". Molecular and Cellular Biology.
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27. (August 1997). "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.
28. (August 2000). "Both corepressor proteins SMRT and N-CoR exist in large protein complexes containing HDAC3". The EMBO Journal.
29. (January 2000). "Nuclear receptor corepressors partner with class II histone deacetylases in a Sin3-independent repression pathway". Genes & Development.
30. (February 2000). "A role for SKIP in EBNA2 activation of CBF1-repressed promoters". Journal of Virology.
31. (April 2000). "SKIP, a CBF1-associated protein, interacts with the ankyrin repeat domain of NotchIC To facilitate NotchIC function". Molecular and Cellular Biology.
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34. (December 2002). "Assembly of the SMRT-histone deacetylase 3 repression complex requires the TCP-1 ring complex". Genes & Development.
35. (May 2000). "A core SMRT corepressor complex containing HDAC3 and TBL1, a WD40-repeat protein linked to deafness". Genes & Development.
36. (October 1998). "Lack of coactivator interaction can be a mechanism for dominant negative activity by mutant thyroid hormone receptors". Endocrinology.
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39. (December 2002). "AML-associated translocation products block vitamin D(3)-induced differentiation by sequestering the vitamin D(3) receptor". Cancer Research.
40. (October 1998). "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.
41. (June 2004). "The Flt3 internal tandem duplication mutant inhibits the function of transcriptional repressors by blocking interactions with SMRT". Blood.