Abstract:
:Thyroid hormone (T(3)) activates nuclear receptor transcription factors, encoded by the TRalpha (NR1A1) and TRbeta (NR1A2) genes, to regulate target gene expression. Several TR isoforms exist, and studies of null mice have identified some unique functions for individual TR variants, although considerable redundancy occurs, raising questions about the specificity of T(3) action. Thus, it is not known how diverse T(3) actions are regulated in target tissues that express multiple receptor variants. I have identified two novel TRbeta isoforms that are expressed widely and result from alternative mRNA splicing. TRbeta3 is a 44.6-kDa protein that contains an unique 23-amino-acid N terminus and acts as a functional receptor. TRDeltabeta3 is a 32.8-kDa protein that lacks a DNA binding domain but retains ligand binding activity and is a potent dominant-negative antagonist. The relative concentrations of beta3 and Deltabeta3 mRNAs vary between tissues and with changes in thyroid status, indicating that alternative splicing is tissue specific and T(3) regulated. These data provide novel insights into the mechanisms of T(3) action and define a new level of specificity that may regulate thyroid status in tissue.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Williams GRdoi
10.1128/mcb.20.22.8329-8342.2000subject
Has Abstractpub_date
2000-11-01 00:00:00pages
8329-42issue
22eissn
0270-7306issn
1098-5549journal_volume
20pub_type
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