Dynamic inhibition of nuclear receptor activation by corepressor binding

Young Chang Sohn, Seung Whan Kim, Seunghee Lee, Young Yun Kong, Doe Sun Na, Soo-Kyung Lee, Jae Lee

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Nuclear receptors adopt dramatically different conformations in the presence or absence of ligand, and such liganded (holo) and unliganded (apo) receptors are specifically recognized by transcriptional coactivators and corepressors, respectively. These two states likely exist in dynamic equilibrium, contrary to the conventional model of static off and on conformations. First, corepressor SMRT [for silencing mediator of thyroid hormone receptor (TR) and retinoic acid receptor (RAR)] inhibits the interaction of coactivator steroid receptor coactivator-1 with liganded TR/RAR. Second, SMRT enables receptors to adopt apo-form even in the presence of ligand, as demonstrated with limited proteolyses and decreased binding of radiolabeled retinoid to RAR. Finally, chromatin immunoprecipitation results indicate that SMRT and steroid receptor coactivator-1 dynamically compete for receptor bindings in vivo in the presence of ligand. These results suggest that corepressor binding can drive receptors to adopt the apo-state, even in the presence of ligand, and inhibit activated liganded (holo) nuclear receptors in vivo.

Original languageEnglish (US)
Pages (from-to)366-372
Number of pages7
JournalMolecular Endocrinology
Volume17
Issue number3
DOIs
StatePublished - Mar 1 2003
Externally publishedYes

Fingerprint

Co-Repressor Proteins
Retinoic Acid Receptors
Nuclear Receptor Coactivator 1
Ligands
Thyroid Hormone Receptors
Cytoplasmic and Nuclear Receptors
Chromatin Immunoprecipitation
Retinoids
Proteolysis

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism

Cite this

Dynamic inhibition of nuclear receptor activation by corepressor binding. / Sohn, Young Chang; Kim, Seung Whan; Lee, Seunghee; Kong, Young Yun; Na, Doe Sun; Lee, Soo-Kyung; Lee, Jae.

In: Molecular Endocrinology, Vol. 17, No. 3, 01.03.2003, p. 366-372.

Research output: Contribution to journalArticle

Sohn, Young Chang ; Kim, Seung Whan ; Lee, Seunghee ; Kong, Young Yun ; Na, Doe Sun ; Lee, Soo-Kyung ; Lee, Jae. / Dynamic inhibition of nuclear receptor activation by corepressor binding. In: Molecular Endocrinology. 2003 ; Vol. 17, No. 3. pp. 366-372.
@article{17a174f56124413687090c9b4908607f,
title = "Dynamic inhibition of nuclear receptor activation by corepressor binding",
abstract = "Nuclear receptors adopt dramatically different conformations in the presence or absence of ligand, and such liganded (holo) and unliganded (apo) receptors are specifically recognized by transcriptional coactivators and corepressors, respectively. These two states likely exist in dynamic equilibrium, contrary to the conventional model of static off and on conformations. First, corepressor SMRT [for silencing mediator of thyroid hormone receptor (TR) and retinoic acid receptor (RAR)] inhibits the interaction of coactivator steroid receptor coactivator-1 with liganded TR/RAR. Second, SMRT enables receptors to adopt apo-form even in the presence of ligand, as demonstrated with limited proteolyses and decreased binding of radiolabeled retinoid to RAR. Finally, chromatin immunoprecipitation results indicate that SMRT and steroid receptor coactivator-1 dynamically compete for receptor bindings in vivo in the presence of ligand. These results suggest that corepressor binding can drive receptors to adopt the apo-state, even in the presence of ligand, and inhibit activated liganded (holo) nuclear receptors in vivo.",
author = "Sohn, {Young Chang} and Kim, {Seung Whan} and Seunghee Lee and Kong, {Young Yun} and Na, {Doe Sun} and Soo-Kyung Lee and Jae Lee",
year = "2003",
month = "3",
day = "1",
doi = "10.1210/me.2002-0150",
language = "English (US)",
volume = "17",
pages = "366--372",
journal = "Molecular Endocrinology",
issn = "0888-8809",
publisher = "The Endocrine Society",
number = "3",

}

TY - JOUR

T1 - Dynamic inhibition of nuclear receptor activation by corepressor binding

AU - Sohn, Young Chang

AU - Kim, Seung Whan

AU - Lee, Seunghee

AU - Kong, Young Yun

AU - Na, Doe Sun

AU - Lee, Soo-Kyung

AU - Lee, Jae

PY - 2003/3/1

Y1 - 2003/3/1

N2 - Nuclear receptors adopt dramatically different conformations in the presence or absence of ligand, and such liganded (holo) and unliganded (apo) receptors are specifically recognized by transcriptional coactivators and corepressors, respectively. These two states likely exist in dynamic equilibrium, contrary to the conventional model of static off and on conformations. First, corepressor SMRT [for silencing mediator of thyroid hormone receptor (TR) and retinoic acid receptor (RAR)] inhibits the interaction of coactivator steroid receptor coactivator-1 with liganded TR/RAR. Second, SMRT enables receptors to adopt apo-form even in the presence of ligand, as demonstrated with limited proteolyses and decreased binding of radiolabeled retinoid to RAR. Finally, chromatin immunoprecipitation results indicate that SMRT and steroid receptor coactivator-1 dynamically compete for receptor bindings in vivo in the presence of ligand. These results suggest that corepressor binding can drive receptors to adopt the apo-state, even in the presence of ligand, and inhibit activated liganded (holo) nuclear receptors in vivo.

AB - Nuclear receptors adopt dramatically different conformations in the presence or absence of ligand, and such liganded (holo) and unliganded (apo) receptors are specifically recognized by transcriptional coactivators and corepressors, respectively. These two states likely exist in dynamic equilibrium, contrary to the conventional model of static off and on conformations. First, corepressor SMRT [for silencing mediator of thyroid hormone receptor (TR) and retinoic acid receptor (RAR)] inhibits the interaction of coactivator steroid receptor coactivator-1 with liganded TR/RAR. Second, SMRT enables receptors to adopt apo-form even in the presence of ligand, as demonstrated with limited proteolyses and decreased binding of radiolabeled retinoid to RAR. Finally, chromatin immunoprecipitation results indicate that SMRT and steroid receptor coactivator-1 dynamically compete for receptor bindings in vivo in the presence of ligand. These results suggest that corepressor binding can drive receptors to adopt the apo-state, even in the presence of ligand, and inhibit activated liganded (holo) nuclear receptors in vivo.

UR - http://www.scopus.com/inward/record.url?scp=0037341820&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037341820&partnerID=8YFLogxK

U2 - 10.1210/me.2002-0150

DO - 10.1210/me.2002-0150

M3 - Article

C2 - 12554786

AN - SCOPUS:0037341820

VL - 17

SP - 366

EP - 372

JO - Molecular Endocrinology

JF - Molecular Endocrinology

SN - 0888-8809

IS - 3

ER -