Linked Life Data

19477412

Source:http://linkedlifedata.com/resource/pubmed/id/19477412

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2009-5-29
pubmed:abstractText
Retinoic acid receptors (RARs) are ligand-dependent transcription factors that control a plethora of physiological processes. RARs exert their functions by regulating gene networks controlling cell growth, differentiation, survival, and death. Uncovering the molecular details by which synthetic ligands direct specificity and functionality of nuclear receptors is key to rational drug development. Here we define the molecular basis for (E)-4-[2-[5,6-Dihydro-5,5-dimethyl-8-(2-phenylethynyl)naphthalen-2-yl]ethen-1-yl]benzoic acid (BMS204,493) acting as the inverse pan-RAR agonist and define 4-[5,6-Dihydro-5,5-dimethyl-8-(quinolin-3-yl)naphthalen-2-carboxamido]benzoic acid (BMS195,614) as the neutral RARalpha-selective antagonist. We reveal the details of the differential coregulator interactions imposed on the receptor by the ligands and show that the anchoring of H12 is fundamentally distinct in the presence of the two ligands, thus accounting for the observed effects on coactivator and corepressor interactions. These ligands will facilitate studies on the role of the constitutive activity of RARs, particularly of the tumor suppressor RARbeta, whose specific functions relative to other RARs have remained elusive.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1879-1301
pubmed:author
pubmed:issnType
Electronic
pubmed:day
29
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
479-89
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Differential action on coregulator interaction defines inverse retinoid agonists and neutral antagonists.
pubmed:affiliation
Department of Cancer Biology, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't