Coactivator recruitment

Desclozeaux M, et al. Phosphorylation and intramolecular stabilization of the ligand binding domain in the nuclear receptor steroidogenic factor 1. Mol. CeU Biol. 2002 22 7193-7203. Wansa KD, Harris JM, Muscat GE. The activation function-1 domain of Nur77/NR4A1 mediates trans-activation, cell specificity, and coactivator recruitment. J. Biol. Chem. 2002 277 33001-33011. 

Wansa KD, et al. The AP-1 domain of the orphan nuclear receptor NOR-1 mediates trans-activation, coactivator recruitment, and activation by the purine anti-metabolite 6-mercaptopurine. J. Biol. Chem. 2003 278 24776-247790. 

Maira M, et al. Dimer-specific potentiation of NGFI-B (Nur77) transcriptional activity by the protein kinase A pathway and AF-l-dependent coactivator recruitment. Mol. Cell Biol. 2003 23 763-776. 

Figure 31.28 Coactivator recruitment, the binding of ligand to a nuclear hormone receptor induces a conformational change in the ligand-binding domain. This change in conformation generates favorable sites for the binding of a coactivator.

Cunha Lima, S.T., Webb, P., Baxter, J.D. and Scanlan, T.S. (2002) Rational design and synthesis of a novel thyroid hormone antagonist that blocks coactivator recruitment. Journal of Medicinal Chemistry, 45, 3310—3320. 

FIGURE 5.6 Ligand-induced AF-2 conformational change and coactivator recruitment. 

Essentially the functional counterpart of coactivators, corepressor proteins bind to many NRs in the absence of ligand and serve to repress basal transcriptive activity [62], Corepressors play a particularly important role for NRs that are found almost exclusively in the nucleus, unlike the apo steroid receptors that are cytoplasmically localized. Studies involving the nuclear-localized receptors TR and RAR led to the identification of silencing mediator of retinoid and thyroid (SMRT) receptors and nuclear receptor corepressor (NCoR) [63, 64]. Both SMRT and NCoR recruit histone deacetylases (HDACs), namely, HDAC3, which function to reverse the chromatin unwinding result of the coactivator-recruited histone acetylases [65],... 

No indication of activation of human PXR and PPARa nuclear receptors or activation of TRP, LXRa, LXRP, and FXR coactivator recruitment... 

Dual-label TR-FRET substrates have also been used for simultaneous monitoring of the enzymes related to apoptosis caspases 1, 3, and 6 [44]. Kokko et al. utilized fluorescent terbium chelates as the donors for two different acceptors, Alexa Fluor 488 and 680, in a dual-label immtmoassay of free and total PSA [45]. Free, uncomplexed PSA were measured with TR-FRET from terbium labeled (universal) antibody to free-specific Alexa 488 labeled antibody, and the total PSA was quantified with TR-FRET from terbium to another generic antibody labeled with Alexa 680. Kupcho et al. followed nuclear receptor coactivator recruitment... 

---