Thyroid hormone receptor coactivator

Monden T, Wondisford FE, Hollenberg AN (1997) Isolation and characterization of a novel ligand-dependent thyroid hormone receptor-coactivating protein. J Biol Chem 272 29834-29841 Moore SD, Herrick SR, Ince TA, Kleinman MS, Cin PD, Morton CC, Quade BJ (2004) Uterine leiomyomata with t(10 17) disrupt the histone acetyltransferase MORF. Cancer Res 64 5570-5577... 

FondelL J- D Ge, J f and Roeder, R. G. (1996), Ligand induction of a transcriptionally active thyroid hormone receptor coactivator compleK- Pfoc- Nati ActiJ, SfJ. U-S-A. 93, 8329-8333. 

Monden T, Wondisford FE, Hollenberg AN. 1997. Isolation and characterization of a novel ligand-dependent thyroid hormone receptor-coactivating protein. J. Biol. Chem. 272 29834 41... 

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. 

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.

Jeyakumar, M. and Katzenellenbogen, J.A. 2009. A dual-acceptor time-resolved Forster resonance energy transfer assay for simultaneous determination of thyroid hormone regulation of corepressor and coactivator binding to the thyroid hormone receptor. Anal. Biochem. 386, 73-78. 

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. 

Ko L, Cardona GR, Chin WW. Thyroid hormone receptor-binding protein, an UOCLL motif-containing protein, functions as a general coactivator. Proc Natl Acad Sci USA 2000 97(11) 6212-6217. 

Thyroid hormone, 1,25-dihydroxy vitamin D, and retinoic acid receptor regulation of transcription. The hormone receptor (HR) is dimerized at site (3) and is bound to DNA at hormone response element site (2). Without the ligand, transcription is inactive due to the interaction of HR with corepressor at site 4. When the ligand (hormone) binds to HR, the bound corepressor dissociates leading to an interaction between the coactivator and HR. These regulatory changes result in increased transcription. 

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