Nuclear receptor coregulators as a new paradigm for therapeutic targeting

Elaine Y. Hsia, Michael L. Goodson, June X Zou, Martin L. Privalsky, Hongwu Chen

Research output: Contribution to journalArticle

39 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)1227-1237
Number of pages11
JournalAdvanced Drug Delivery Reviews
Volume62
Issue number13
DOIs
StatePublished - Oct 30 2010

Fingerprint

Co-Repressor Proteins
Cytoplasmic and Nuclear Receptors
Histones
Chromatin Assembly and Disassembly
Metabolic Diseases
Acetylation
Epigenomics
Methylation
Chromatin
Therapeutics

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 journalArticle

Hsia, Elaine Y. ; Goodson, Michael L. ; Zou, June X ; Privalsky, Martin L. ; Chen, Hongwu. / Nuclear receptor coregulators as a new paradigm for therapeutic targeting. In: Advanced Drug Delivery Reviews. 2010 ; Vol. 62, No. 13. pp. 1227-1237.
@article{fe3d1dc111954e1687482fc6eddde0ae,
title = "Nuclear receptor coregulators as a new paradigm for therapeutic targeting",
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.",
keywords = "ANCCA, Cancer, Diabetes, Histone acetylation, Histone methylation, NCoR, Obesity, P160/SRC, PGC-1, SMRT",
author = "Hsia, {Elaine Y.} and Goodson, {Michael L.} and Zou, {June X} and Privalsky, {Martin L.} and Hongwu Chen",
year = "2010",
month = "10",
day = "30",
doi = "10.1016/j.addr.2010.09.016",
language = "English (US)",
volume = "62",
pages = "1227--1237",
journal = "Advanced Drug Delivery Reviews",
issn = "0169-409X",
publisher = "Elsevier",
number = "13",

}

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

C2 - 20933027

AN - SCOPUS:78649326873

VL - 62

SP - 1227

EP - 1237

JO - Advanced Drug Delivery Reviews

JF - Advanced Drug Delivery Reviews

SN - 0169-409X

IS - 13

ER -