Abstract
The thyroid hormone receptor (TR) directly regulates the transcription of thyroid hormone-responsive genes in response to changing levels of thyroid hormone. Mechanistically TR utilizes a complex set of binding interactions, with hormone, response elements, and coregulatory proteins, to provide specific local control of patterns of transcriptional response that are partially responsible for inducing the tissue-selective responses to the circulating hormone. One of the apparently dominant phenomena in the regulation of thyroid hormone responses is the protein interactions between TR and its coregulators. This review summarizes the current state of knowledge with respect to the identity of these coregulators, their interaction with TR, and the consequences of those interactions.
Highlights
The thyroid hormone receptor (TR) directly regulates the transcription of thyroid hormone-responsive genes in response to changing levels of thyroid hormone
Most of the effects of thyroid hormone (TH)1 are relatively slow in onset and mediated by a family of high affinity receptor proteins known as the thyroid hormone receptors (TRs) that act directly as transcription factors [3]
Recent work has demonstrated that metabolites of thyroid hormone can exert rapid biological effects through the G-protein-coupled receptors that act through secondary messenger pathways [4]
Summary
The thyroid hormone receptor (TR) directly regulates the transcription of thyroid hormone-responsive genes in response to changing levels of thyroid hormone. One striking feature of the knock-out studies is that deletion of both TR␣ and TR induces only mild hypothyroidism and relatively viable animals, much more so than many of the single knock-outs (14 –17) This points to the importance of repression of transcription by unliganded TR as a mecha-. Upon binding of thyroid hormone, TR undergoes a conformational change, releasing corepressor proteins and allowing for the interaction with coactivator proteins that enhance TRE-driven gene transcription (Fig. 1B) [22]. It is the control of the interactions of the TR with its coregulatory proteins that defines the transcription of individual genes. We focus on defining TR coregulator interactions by organizing the available data and providing simple conclusions about the potential in vivo affects of TR coregulators
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