Thyroid hormone receptor coactivator complex

Fondell, J. D., Ge, H., and Roeder, R. G. (1996). Ligand induction of a transcriptionally active thyroid hormone receptor coactivator complex. Proc. Natl. Acad. Sci. U.S.A. 93, 8329-8333. 

Beside coactivators so-called corepressors exist that are bound to transcription factors such as nuclear receptors and inhibit the initiation of transcription. These factors include the nuclear receptor corepressor (NCoR) and the silencing mediator of retinoic acid and thyroid hormone receptor (SMRT), which interact with nuclear receptors and serve as platforms for complexes containing histone deacetylases (HDACs). These enzymes cause the reversal of histone acetylation of histones leading to a tightening of chromatin and enhancing its inaccessibility for RNA polymerase containing complexes. 

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)... 

A series of proteins or protein complexes with coactivator function for nuclear receptors has been identified that specifically interact with the activated, liganded receptor. The most abundant ones are now included in the pl60 family of coactivators with the steroid receptor coactivator 1, SRC-1, as a well-characterized member. Another group of coactivators is present as multiprotein complexes like the TRAP complex (TRAP, thyroid hormone receptor activating protein). A common receptor interaction motif LXXLL is found on these coactivators which mediates at least part of the interaction with the AF2 domain of the receptor. 

Jeyakumar and Katzenellenbogen developed a dual-acceptor assay to monitor a nuclear receptor (thyroid hormone - retinoid X receptor heterodimer) regulation by measuring both coactivator and corepressor binding by using fluorescein and Cy-5 as acceptors for a terbium chelate-labeled response element-bound receptor complex [47]. 

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