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PMID: 9742089 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Transcriptional silencing is defined by isoform- and heterodimer-specific interactions between nuclear hormone receptors and corepressors.

Molecular and cellular biology ·Vol. 18 ·No. 10 ·1998-10-00 ·Pages 5724-33

Wong CW, Privalsky ML

Abstract

Nuclear hormone receptors are ligand-regulated transcription factors that play critical roles in metazoan homeostasis, development, and reproduction. Many nuclear hormone receptors exhibit bimodal transcriptional properties and can either repress or activate the expression of a given target gene. Repression appears to require a physical interaction between a receptor and a corepressor complex containing the SMRT/TRAC or N-CoR/RIP13 polypeptides. We wished to better elucidate the rules governing the association of receptors with corepressors. We report here that different receptors interact with different domains in the SMRT and N-CoR corepressors and that these divergent interactions may therefore contribute to distinct repression phenotypes. Intriguingly, different isoforms of a single nuclear hormone receptor class also differ markedly in their interactions with corepressors, indicative of their nonidentical actions in cellular regulation. Finally, we present evidence that combinatorial interactions between different receptors can, through the formation of heterodimeric receptors, result in novel receptor-corepressor interactions not observed for homomeric receptors.

MeSH Terms
Amino Acid Sequence Animals Binding Sites Cell Line Cell Nucleus/metabolism Chlorocebus aethiops DNA-Binding Proteins/genetics,metabolism Dimerization Humans Molecular Sequence Data Nuclear Proteins/genetics,metabolism Nuclear Receptor Co-Repressor 1 Nuclear Receptor Co-Repressor 2 Receptors, Cell Surface/metabolism Receptors, Retinoic Acid/metabolism Repressor Proteins/genetics,metabolism Retinoic Acid Receptor alpha Transcription, Genetic
Chemicals
DNA-Binding Proteins NCOR1 protein, human NCOR2 protein, human Nuclear Proteins Nuclear Receptor Co-Repressor 1 Nuclear Receptor Co-Repressor 2 RARA protein, human Receptors, Cell Surface Receptors, Retinoic Acid Repressor Proteins Retinoic Acid Receptor alpha retinoic acid receptor beta retinoic acid receptor gamma
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Wong C W
Section of Microbiology, Division of Biological Sciences, University of California at Davis, Davis, California 95616, USA.
Privalsky M L
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.18.10.5724
Published
1998-10-00
Pages
5724-33
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC109158
Subset
IM
Grants
NCI NIH HHS · CA53394 · United States
External Links
PubMed source DOI: 10.1128/MCB.18.10.5724 PMC Full Text View journal details
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