Thyroid hormone receptors are hormone-regulated transcription factors that play key roles in normal vertebrate physiology and development. Thyroid hormone receptors can either repress or activate target gene expression, reflecting their ability to alternatively recruit corepressor and coactivator proteins; these coregulators, in turn, confer the specific molecular events responsible for the modulation of target gene expression. Notably, defects in this coregulator exchange manifest as human endocrine and neoplastic disease. This chapter describes the machinery that underlies transcriptional regulation by the normal thyroid hormone receptors, and the aberrations in this machinery that result in resistance to thyroid hormone, erythroleukemia, hepatocellular carcinoma, renal clear cell carcinoma, and thyroid neoplasia. Intriguingly, these diseases appear to share a common molecular flaw: an improper retention of corepressor by mutant thyroid hormone receptors under circumstances in which the wild-type receptors release corepressor and acquire coactivators. The implications of these observations are discussed.
|Original language||English (US)|
|Title of host publication||NR Coregulators and Human Diseases|
|Publisher||World Scientific Publishing Co.|
|Number of pages||38|
|ISBN (Print)||9812705368, 9789812705365|
|State||Published - Jan 1 2008|
ASJC Scopus subject areas