Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
|
| pubmed:dateCreated |
1995-6-26
|
| pubmed:abstractText |
The functionally inactive thyroid hormone receptor splicing variant-alpha 2 (TRv alpha 2) can inhibit transcriptional activation by TR alpha 1 or beta 1, demonstrating a dominant negative effect (DNE). We examine here the three commonly proposed mechanisms, namely, competition for binding to thyroid hormone response elements (TREs), formation of inactive heterodimers, and squelching. A mutation introduced into the DNA-binding domain (DBD) of the TRv alpha 2 was designed to prevent its binding to TREs. In transient cotransfection studies, the DBD mutant has nearly the same DNE as does TRv alpha 2 on three different TRE-containing reporter genes. The DNE of TRv alpha 2 is also not reversed by cotransfection with excess retinoid X receptor-alpha. Extracts of COS cells cotransfected with TR alpha 1 and either TRv alpha 2 or DBD mutant at different ratios were analyzed by gel shift assays. Neither TRv alpha 2 or the mutant altered binding of TR alpha 1 to four radiolabeled TREs. TRv alpha 2 itself can inhibit constitutive transactivation by a thymidine kinase promoter-driven reporter construct. Our results suggest that TRv alpha 2 can function in a dominant negative manner without binding to a TRE, at least for certain TREs. It is concluded that the DNE of TRv alpha 2 may occur through another unrecognized mechanism, perhaps by binding to basal transcription factors.
|
| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jan
|
| pubmed:issn |
0888-8809
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
9
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
86-95
|
| pubmed:dateRevised |
2008-11-21
|
| pubmed:meshHeading |
pubmed-meshheading:7760853-Animals,
pubmed-meshheading:7760853-Base Sequence,
pubmed-meshheading:7760853-Carcinoma, Hepatocellular,
pubmed-meshheading:7760853-Cell Line, Transformed,
pubmed-meshheading:7760853-Cercopithecus aethiops,
pubmed-meshheading:7760853-DNA,
pubmed-meshheading:7760853-Depression, Chemical,
pubmed-meshheading:7760853-Gene Expression Regulation,
pubmed-meshheading:7760853-Humans,
pubmed-meshheading:7760853-Liver Neoplasms,
pubmed-meshheading:7760853-Molecular Sequence Data,
pubmed-meshheading:7760853-Mutagenesis, Site-Directed,
pubmed-meshheading:7760853-Protein Binding,
pubmed-meshheading:7760853-RNA Splicing,
pubmed-meshheading:7760853-Receptors, Thyroid Hormone,
pubmed-meshheading:7760853-Recombinant Fusion Proteins,
pubmed-meshheading:7760853-Regulatory Sequences, Nucleic Acid,
pubmed-meshheading:7760853-Transcriptional Activation,
pubmed-meshheading:7760853-Tumor Cells, Cultured
|
| pubmed:year |
1995
|
| pubmed:articleTitle |
The dominant negative effect of thyroid hormone receptor splicing variant alpha 2 does not require binding to a thyroid response element.
|
| pubmed:affiliation |
Department of Medicine, University of Chicago, Illinois 60637, USA.
|
| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|