Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2
|
| pubmed:dateCreated |
1998-3-30
|
| pubmed:abstractText |
Rev-erbA alpha and RVR are orphan nuclear receptors that function as dominant transcriptional silencers. Ligand-independent repression of transcription by Rev-erbA alpha and RVR is mediated by the nuclear receptor corepressors, N-CoR and its variants RIP (RXR interacting protein) 13a and RIP13 delta 1. The physical association between the corepressors and Rev-erbA alpha and RVR is dependent on the presence of a receptor interaction domain (RID) in the N-CoR family. Our previous study demonstrated that the E region of RVR and Rev-erbA alpha is necessary and sufficient for the in vivo interaction with the nuclear receptor corepressor, RIP13 delta 1. The present investigation demonstrates that two corepressor interaction regions, CIR-1 and CIR-2, separated by approximately 150 amino acids in the E region of RVR, are required for the interaction with N-CoR, RIP13a, and RIP13 delta A. The D region is not required for the physical interaction. In contrast, the D and E regions of Rev-erbA alpha were necessary for the interaction with the N-CoR and RIP13a-RIDs in vivo, suggesting that RIP13 delta 1 and N-CoR/RIP13a differentially interact with Rev-erbA alpha. Mutagenesis of CIR-1, a novel domain that is highly conserved between RVR and Rev-erbA alpha, demonstrated that the N-terminal portion of helix 3 plays a key role and is absolutely necessary for the interaction with RIP13 delta 1, RIP13a, and N-CoR. The phenylalanine residues, F402 and F441, in RVR and Rev-erbA alpha, respectively, were critical residues in supporting corepressor interaction. Cotransfection studies demonstrated that repression of a physiological target, the human Rev-erbA alpha promoter, by RVR was significantly impaired by mutation of CIR-1 or deletion of CIR-2. Furthermore, overexpression of either the N-CoR/RIP13a or RIP13 delta 1-RIDs alleviated RVR-mediated repression of the Rev-erbA alpha promoter, demonstrating that corepressor binding mediates the repression of a native target gene by RVR. A minimal region containing juxtapositioned CIR-1 and CIR-2 was sufficient for corepressor binding and transcriptional repression. In conclusion, our study has identified a new corepressor interaction region, CIR-1, in the N terminus of helix 3 in the E region of RVR and Rev-erbA alpha, that is required for transcriptional silencing. Furthermore, we provide evidence that CIR-1 and CIR-2 may form a single corepressor interaction interface.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/NCOR1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/NR1D1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Ncor1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nr1d1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Receptor Co-Repressor 1,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Receptor Subfamily 1...,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Thyroid Hormone,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Feb
|
| pubmed:issn |
0888-8809
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
12
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
248-62
|
| pubmed:dateRevised |
2009-11-19
|
| pubmed:meshHeading |
pubmed-meshheading:9482666-Amino Acid Sequence,
pubmed-meshheading:9482666-Animals,
pubmed-meshheading:9482666-Choriocarcinoma,
pubmed-meshheading:9482666-DNA-Binding Proteins,
pubmed-meshheading:9482666-Humans,
pubmed-meshheading:9482666-Mice,
pubmed-meshheading:9482666-Molecular Sequence Data,
pubmed-meshheading:9482666-Nerve Tissue Proteins,
pubmed-meshheading:9482666-Nuclear Proteins,
pubmed-meshheading:9482666-Nuclear Receptor Co-Repressor 1,
pubmed-meshheading:9482666-Nuclear Receptor Subfamily 1, Group D, Member 1,
pubmed-meshheading:9482666-Protein Binding,
pubmed-meshheading:9482666-Protein Structure, Secondary,
pubmed-meshheading:9482666-Protein Structure, Tertiary,
pubmed-meshheading:9482666-Proteins,
pubmed-meshheading:9482666-Receptors, Cytoplasmic and Nuclear,
pubmed-meshheading:9482666-Receptors, Thyroid Hormone,
pubmed-meshheading:9482666-Repressor Proteins,
pubmed-meshheading:9482666-Tumor Cells, Cultured
|
| pubmed:year |
1998
|
| pubmed:articleTitle |
Identification and characterization of a novel corepressor interaction region in RVR and Rev-erbA alpha.
|
| pubmed:affiliation |
University of Queensland, Centre for Molecular and Cellular Biology, Ritchie Research Laboratories, Brisbane, Australia.
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|