The N-Terminal A/B domain of the thyroid hormone receptor-beta2 isoform influences ligand-dependent recruitment of coactivators to the ligand-binding domain

Molecular Endocrinology
Henghe TianHerbert H Samuels

Abstract

Thyroid hormone receptors (TRs), expressed as TRalpha1, TRbeta1, and TRbeta2 isoforms, are members of the steroid hormone nuclear receptor gene superfamily, which comprises ligand-dependent transcription factors. The TR isoforms differ primarily in their N-terminal (A/B) domains, suggesting that the A/B regions mediate distinct transcriptional activation functions in a cell type-dependent or promoter-specific fashion. The nuclear receptor ligand-binding domain (LBD) undergoes a conformational change upon ligand binding that results in the recruitment of coactivators to the LBD. For glucocorticoid receptor and estrogen receptor-alpha, the same coactivator can contact both the LBD and A/B domains, thus leading to enhanced transcriptional activation. Very little is known regarding the role of the A/B domains of the TR isoforms. The A/B domain of TRbeta2 exhibits higher ligand-independent transcriptional activity than the A/B regions of TRalpha1 or TRbeta1. Thus, we examined the role of the A/B domain and the LBD of rat TRbeta2 in integrating the transcriptional activation function of the A/B and LBD domains by different coactivators. Both domains are essential for a productive functional interaction with cAMP response element-bind...Continue Reading

Citations

Feb 1, 2013·Journal of Thyroid Research·Johannes W DietrichElisavet H Fotiadou
Feb 10, 2012·The Journal of Clinical Endocrinology and Metabolism·Alfonso Massimiliano FerraraSamuel Refetoff
Jul 16, 2011·Journal of Thyroid Research·Meghan D Rosen, Martin L Privalsky
Aug 25, 2007·Biochemical and Biophysical Research Communications·Marie-Belle PoirierMarie-France Langlois
May 12, 2009·Molecular and Cellular Endocrinology·Anca Azoitei, Margarethe Spindler-Barth
Jan 6, 2017·The Journal of Endocrinology·Gabriela Hernández-PugaAurea Orozco
Apr 6, 2013·Molecular Endocrinology·Johnnie B Hahm, Martin L Privalsky
Feb 1, 2014·Molecular and Cellular Biochemistry·Rong-Lan ZhaoJing-Yu Zhang
Oct 31, 2017·Pharmacology & Therapeutics·Elias J Fernandez

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