Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
32
pubmed:dateCreated
2002-8-5
pubmed:abstractText
Thyroid hormone receptors (TRs) are critical regulators of growth, differentiation, and homeostasis. TRs function by regulating the expression of thyroid hormone (T3) target genes in both ligand-dependent and -independent pathways. Distinct classes of co-regulatory proteins modulate these two pathways. We show here a novel role of cyclin D1 as a T3-independent co-repressor for TRs. Cyclin D1 interacted with TR in vitro and in cells in a ligand-independent manner. Cyclin D1 acted to repress both the silencing activity of the unliganded TR and the transcriptional activity of the liganded TR. The repression was not due to the inhibition of the binding of TR to the thyroid hormone response element but by serving as a ligand-independent bridging factor to selectively recruit HDAC3 to form ternary complexes. The repression was augmented by increasing expression of HDAC3 but not by HDAC1 and was alleviated by trichostatin A. Thus, cyclin D1 is a novel ligand-independent co-repressor that opens a new paradigm to understand the molecular basis of the silencing action of TR.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
9
pubmed:volume
277
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
28733-41
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:12048199-Animals, pubmed-meshheading:12048199-Blotting, Western, pubmed-meshheading:12048199-Cell Line, pubmed-meshheading:12048199-Cyclin D1, pubmed-meshheading:12048199-Dimerization, pubmed-meshheading:12048199-Enzyme Inhibitors, pubmed-meshheading:12048199-Genes, Reporter, pubmed-meshheading:12048199-Glutathione Transferase, pubmed-meshheading:12048199-Histone Deacetylase Inhibitors, pubmed-meshheading:12048199-Histone Deacetylases, pubmed-meshheading:12048199-Humans, pubmed-meshheading:12048199-Hydroxamic Acids, pubmed-meshheading:12048199-Ligands, pubmed-meshheading:12048199-Models, Genetic, pubmed-meshheading:12048199-Plasmids, pubmed-meshheading:12048199-Precipitin Tests, pubmed-meshheading:12048199-Protein Binding, pubmed-meshheading:12048199-Rats, pubmed-meshheading:12048199-Receptors, Thyroid Hormone, pubmed-meshheading:12048199-Recombinant Fusion Proteins, pubmed-meshheading:12048199-Signal Transduction, pubmed-meshheading:12048199-Transcription, Genetic, pubmed-meshheading:12048199-Transcriptional Activation, pubmed-meshheading:12048199-Transfection, pubmed-meshheading:12048199-Tumor Cells, Cultured
pubmed:year
2002
pubmed:articleTitle
Cyclin D1 Is a Ligand-independent Co-repressor for Thyroid Hormone Receptors.
pubmed:affiliation
Gene Regulation Section, Laboratory of Molecular Biology, Center for Cancer Research, NCI, National Institutes of Health, Bethesda, Maryland 20892-4264, USA.
pubmed:publicationType
Journal Article