Thyroid hormone receptor associated protein

J. D. Fondell, M. Guermah, S. Malik, and R G. Roeder. Thyroid hormone receptor-associated proteins and general positive cofactors mediate thyroid hormone receptor function in the absence of the TATA box-binding protein-associated factors of TFIID. Proc Nad Acad. Sci, VSA, 96 (5), 1959-1964, 1999. 

Yuan CX, Ito M, Fondell JD, Fu ZY, Roeder RG. 1998. The TRAP220 component of a thyroid hormone receptor-associated protein (TRAP) coactivator complex interacts directly with nuclear receptors in a ligand dependent fashion. Proc. Natl. Acad Sci. USA 95 7939 14... 

Interaction of the HAT coactivatorcomplex with the ligand-activated receptors is apparently transient as dissociation is believed to occur as a result of acetylation of one or more coactivators on lysine residues adjacent to the signature LXXLL motif (187). Subsequently, the activated receptor presumably recruits a second class of multi-protein, transcriptional coactivator complexes to the template, and this latter complex, referred to as the thyroid hormone receptor-associated protein (TRAP)... 

Burris TP, Nawaz Z, Tsai MJ, O Malley BW. 1995. A nuclear hormone receptor-associated protein that inhibits transactivation by the thyroid hormone and retinoic acid receptors. Proc. Natl. Acad. Sci. USA 92 9525-29... 

Figure 7.4 The effect of bile acids on energy expenditure. Circulating bile acids bind to the G-protein-coupled receptor, TGR5 that stimulates increased cAMP-PKA activation and increased expression of type-2 iodothyronine deiodinase (D2). This response is sensitised by a high-fat diet. D2 converts thyroxine (T4) to active 3,5,3 -tri-iodothyronine (T3). T3 stimulates thyroid hormone receptor binding to target genes. This leads to altered expression of genes associated with energy balance, and increased energy expenditure.

In the absence of ligand, some nuclear hormone receptors associate with co-repressors, namely, SMRT (silencing mediator of retinoic acid and thyroid hormone receptors) and N-CoR (nuclear receptor co-repressor). Both, SMRT and N-CoR, recruit coregulatory protein SINS and histone deacetylases (HDACs) to form a large co-repressor complex that contains histone deacetylase activity, implicating histone deacetylation in transcriptional repression [52,53]. 

Fig. 7. Model for activation by coactivators (A) and inhibition by corepressors (B) of transcription. Abbreviations CBP/p300, cAMP response element binding protein SRC-1, steroid receptor coactivator 1 TBP, TATA-binding protein TAF, TBP-associated factor pol II, RNA polymerase II N-CoR, nuclear receptor corepressor SMRT, silencing mediator of retinoic and thyroid hormone receptors.

Thyroid hormones and most steroid hormones are associated with carrier proteins in the serum. The carrier proteins are called, appropriately, thyroxine-binding globulin, transcortin (for cortisol), and sex-steroid-binding protein. These proteins have a high affinity (Kd 10—9— 10 8 m) for their respective hormones. They buffer the concentration of free hormone and retard hormone degradation and excretion. The carrier proteins are distinguishable from the intracellular receptors for these hormones. 

Lipid-soluble hormones act usually by gene activation/deactivation. Examples of these hormones include steroids, thyroid hormone, and vitamin A (retinoic acid). The hormones are transported through the circulation in association with a hormone-binding protein and are soluble in the plasma membrane of the cell. Their receptors are intracellular, and they act on gene transcription (the synthesis of messenger RNA) rather than at the protein level. Thus, they act more slowly than do the soluble hormones, on the scale of days rather than minutes. 

Tagging and recovery of associated proteins, as in RNA-TRAP also thrombin receptor activation peptide Thyroid hormone response elements Thyrotropin-releasing hormone... 

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