Abstract
The complex function and regulation of nuclear receptors cannot be fully understood without a thorough knowledge of the receptor-associated coregulators that either enhance (coactivators) or inhibit (corepressors) transcription. While nuclear receptors themselves have garnered much attention as therapeutic targets, the clinical and etiological relevance of the coregulators to human diseases is increasingly recognized. Aberrant expression or function of coactivators and corepressors has been associated with malignant and metabolic disease development. Many of them are key epigenetic regulators and utilize enzymatic activities to modify chromatin through histone acetylation/deacetylation, histone methylation/demethylation or chromatin remodeling. In this review, we showcase and evaluate coregulators - such as SRCs and ANCCA - with the most promising therapeutic potential based on their physiological roles and involvement in various diseases that are revealed thus far. We also describe the structural features of the coactivator and corepressor functional domains and highlight areas that can be further explored for molecular targeting.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1227-1237 |
| Number of pages | 11 |
| Journal | Advanced Drug Delivery Reviews |
| Volume | 62 |
| Issue number | 13 |
| DOIs | |
| State | Published - Oct 30 2010 |
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Keywords
- ANCCA
- Cancer
- Diabetes
- Histone acetylation
- Histone methylation
- NCoR
- Obesity
- P160/SRC
- PGC-1
- SMRT
ASJC Scopus subject areas
- Pharmaceutical Science
Cite this
Nuclear receptor coregulators as a new paradigm for therapeutic targeting. / Hsia, Elaine Y.; Goodson, Michael L.; Zou, June X; Privalsky, Martin L.; Chen, Hongwu.
In: Advanced Drug Delivery Reviews, Vol. 62, No. 13, 30.10.2010, p. 1227-1237.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Nuclear receptor coregulators as a new paradigm for therapeutic targeting
AU - Hsia, Elaine Y.
AU - Goodson, Michael L.
AU - Zou, June X
AU - Privalsky, Martin L.
AU - Chen, Hongwu
PY - 2010/10/30
Y1 - 2010/10/30
N2 - The complex function and regulation of nuclear receptors cannot be fully understood without a thorough knowledge of the receptor-associated coregulators that either enhance (coactivators) or inhibit (corepressors) transcription. While nuclear receptors themselves have garnered much attention as therapeutic targets, the clinical and etiological relevance of the coregulators to human diseases is increasingly recognized. Aberrant expression or function of coactivators and corepressors has been associated with malignant and metabolic disease development. Many of them are key epigenetic regulators and utilize enzymatic activities to modify chromatin through histone acetylation/deacetylation, histone methylation/demethylation or chromatin remodeling. In this review, we showcase and evaluate coregulators - such as SRCs and ANCCA - with the most promising therapeutic potential based on their physiological roles and involvement in various diseases that are revealed thus far. We also describe the structural features of the coactivator and corepressor functional domains and highlight areas that can be further explored for molecular targeting.
AB - The complex function and regulation of nuclear receptors cannot be fully understood without a thorough knowledge of the receptor-associated coregulators that either enhance (coactivators) or inhibit (corepressors) transcription. While nuclear receptors themselves have garnered much attention as therapeutic targets, the clinical and etiological relevance of the coregulators to human diseases is increasingly recognized. Aberrant expression or function of coactivators and corepressors has been associated with malignant and metabolic disease development. Many of them are key epigenetic regulators and utilize enzymatic activities to modify chromatin through histone acetylation/deacetylation, histone methylation/demethylation or chromatin remodeling. In this review, we showcase and evaluate coregulators - such as SRCs and ANCCA - with the most promising therapeutic potential based on their physiological roles and involvement in various diseases that are revealed thus far. We also describe the structural features of the coactivator and corepressor functional domains and highlight areas that can be further explored for molecular targeting.
KW - ANCCA
KW - Cancer
KW - Diabetes
KW - Histone acetylation
KW - Histone methylation
KW - NCoR
KW - Obesity
KW - P160/SRC
KW - PGC-1
KW - SMRT
UR - http://www.scopus.com/inward/record.url?scp=78649326873&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=78649326873&partnerID=8YFLogxK
U2 - 10.1016/j.addr.2010.09.016
DO - 10.1016/j.addr.2010.09.016
M3 - Article
VL - 62
SP - 1227
EP - 1237
JO - Advanced Drug Delivery Reviews
JF - Advanced Drug Delivery Reviews
SN - 0169-409X
IS - 13
ER -