Linked Life Data

21050917

Source:http://linkedlifedata.com/resource/pubmed/id/21050917

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2010-11-5
pubmed:abstractText
Nuclear receptors (NRs) are ligand-inducible transcription factors that regulate a plethora of cell biological phenomena, thus orchestrating complex events like development, organ homeostasis, immune function, and reproduction. Due to their regulatory potential, NRs are major drug targets for a variety of diseases, including cancer and metabolic diseases, and had a major societal impact following the development of contraceptives and abortifacients. Not surprisingly in view of this medical and societal importance, a large amount of diverse NR ligands have been generated and the corresponding structural and functional analyses have provided a deep insight into the molecular basis of ligand action. What we have learnt is that ligands regulate, via allosteric conformational changes, the ability of NRs to interact with different sets of coregulators which in turn recruit enzymatically active complexes, the workhorses of the ligand-induced epigenetic and transcription-regulatory events. Thus, ligands essentially direct the communication of a given NR with its intracellular environment at the chromatin and extragenomic level to modulate gene programs directly at the chromatin level or via less well-understood extranuclear actions. Here we will review our current structural and mechanistic insight into the functionalities of subsets of retinoid and rexinoid ligands that act generically as antagonists but follow different mechanistic principles, resulting in "classical" or neutral antagonism, or inverse agonism. In addition, we describe the chemical features and guidelines for the synthesis of retinoids/rexinoids that exert specific functions and we provide protocols for a number of experimental approaches that are useful for studies of the agonistic and antagonistic features of NR ligands.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1557-7988
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 Elsevier Inc. All rights reserved.
pubmed:issnType
Electronic
pubmed:volume
485
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
161-95
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Inverse agonists and antagonists of retinoid receptors.
pubmed:affiliation
INSERM U554 and CNRS UMR5048, Centre de Biochimie Structurale, Universités Montpellier 1 & 2, Montpellier, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't