Thyroid hormone receptors (TRs) belong to the nuclear receptor superfamily (NR). TRs are ligand-regulated transcription factors that also participate in non-genomic signaling pathways. TRs are expressed as three major isoforms (TRα1, TRβ1, TRβ2) which mediate the majority of thyroid hormone effects in mammals. The TR isoforms are found expressed in a tissue-specific manner with overlapping yet distinct biological roles. The TRα1 and TRβ2 isoforms also have unique transcriptional properties that differ from those of TRβ1. To more fully understand the isoform-specific biological and molecular properties of TRs, we have identified a series of previously unrecognized proteins that selectively interact with TRα1 or TRβ2 versus TRβ1. Several of these proteins also preferentially enhance the transcriptional activity of TRβ2, and are likely to represent novel, isoform-specific coactivators. Additional proteins were also identified in our screen to bind equally to all three TR isoforms; these novel binding partners may function as isoform-independent auxiliary proteins for these and/or other NRs. We propose that a combination of isoform-specific recruitment and tissue-specific expression of these newly identified coregulator candidates serve to customize TR function for different biological purposes in different cell types.
|Advisor:||Privalsky, Martin L.|
|Commitee:||Chen, Hongwu, Furlow, John D.|
|School:||University of California, Davis|
|Department:||Biochemistry and Molecular Biology|
|School Location:||United States -- California|
|Source:||DAI-B 74/10(E), Dissertation Abstracts International|
|Subjects:||Biology, Molecular biology, Biochemistry|
|Keywords:||Co-regulators, Coactivators, Coregulators, Corepressors, Isoform-specific, Thyroid hormone receptor|
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