Linked Life Data

9083030

Source:http://linkedlifedata.com/resource/pubmed/id/9083030

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
14
pubmed:dateCreated
1997-5-8
pubmed:abstractText
Human thyroid hormone nuclear receptor isoforms (TRalpha1 and TRbeta1) express differentially in a tissue-specific and development-dependent manner. It is unclear whether these two isoforms have differential functions. We analyzed their interaction with a thyroid hormone response element with half-site binding motifs arranged in an everted repeat separated by six nucleotides (F2). Despite extensive sequence homologies, the two isoforms bound to F2 with different affinities and ratios of homodimer/monomer. Using F2-containing reporter gene, we found that the transcriptional activity of TRbeta1 was approximately 6-fold higher than that of TRalpha1. The lower activity of TRalpha1 was not due to differences in expression of the two isoforms because similar nuclear localization patterns were observed. To understand the structural determinants responsible for these differences, we constructed chimeric receptors in which hinge regions (domain D), hormone binding domains (domain E), and domains (D + E) were sequentially interchanged and their activities were compared. Chimeric TRs containing the domains D, E or (D + E) of TRbeta1 showed increased propensities to form homodimers and mediated higher transactivation activities than TRalpha1. Thus, differential transactivation activities of TR isoforms are mediated by interplay of their domains and could serve as an important regulatory mechanism to achieve diversity and specificity of pleiotropic T3 effect.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
4
pubmed:volume
272
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
9048-54
pubmed:dateRevised
2005-11-17
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
The differential hormone-dependent transcriptional activation of thyroid hormone receptor isoforms is mediated by interplay of their domains.
pubmed:affiliation
Laboratory of Molecular Biology, Division of Basic Sciences, NIDDKD, National Institutes of Health, Bethesda, Maryland 20892, USA.
pubmed:publicationType
Journal Article