Year: 2000
Type: article
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.
Source: Molecular and Cellular Biology
Author: Graham R. Williams
Institutions: Hammersmith Hospital, Imperial College London
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: Wellcome Trust, Medical Research Council
Award: G3231192968
OpenAlex ID: W1988348937