Nuclear hormone receptor activator

Forman BM, Evans RM. 1995. Nuclear hormone receptors activate direct, inverted, and everted repeats. Ann. NY Acad. Sci. 761 29-37... 

Dedhar S, Rennie PS, Shago M, Hag-esteijn CY, Yang H, et al. 1994. Inhibition of nuclear hormone receptor activity by calreticulin. Nature 367(6462) 480-83... 

The steroid receptor family is a subclass of nuclear hormone receptors activated by steroid hormones. This nuclear hormone receptor subfamily has six members ... 

The antagonist-induced conformation of nuclear hormone receptors attracts co-repressors like Nco/SMRT (nuclear hormone receptor co-repressor/silencing mediator of retinoid and thyroid receptors) which further recruit other nuclear proteins with histone deacetylase activity. Their action leads to chromatin condensation, thus preventing the general transcription apparatus from binding to promoter regions. 

SaOS-2 osteoblasts (Kim et al., 2003). Such an effect was shown to be dependent on the stage of cell differentiation. The mechanism of the differentiating activity of lycopene is still unclear. One of the most reliable hypothesis is that the carotenoid may activate the expression of nuclear hormone receptors, such as RAR and RXR (Sharoni et al., 2002). 

The farnesoid X receptor is a member of the class of nuclear hormone receptors, which have key roles in development and homeostasis, as well as in many diseases like obesity, diabetes and cancer. The farnesoid X receptor shows structural similarity to the estrogen receptor (ER ), which mediates a broad spectrum of physiological functions such as regulation of reproduction, modulation of bone density, cholesterol transport and breast cancer. The farnesoid X receptor also shows similarity with the peroxisome proliferation-activated receptor y (PPARy), which is involved in fat metabolism, inflammatory and immune responses. The estrogen receptor (ER ), the peroxisome proliferation-activated receptor y (PPARy) and the farnesoid X receptor (FXR) can be clustered in a... 

Nuclear receptors exert their different transcriptional functions through interactions with and the recruitment of co-factors to responsive promoters. Co-factors are either positive or negative regulatory proteins and are classified as co-activators, which promote, or co-repressors, which attenuate the activity of nuclear hormone receptors [46]. The molecular mechanisms that regulate the mutually exclusive interactions of the nuclear receptor with either class of co-factors have been analysed by crystallographic studies. Functional and structural studies have shown that co-activators interact with the transactivation function (AF) of nuclear hormone receptors via short, leucine-rich motifs (LXXLL) termed NR boxes , thereby transducing hormonal signals to the basal transcription machinery [47]. 

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. 4 Co-activator and co-repressor complexes are required for nuclear hormone receptor-mediated transcriptional regulation. The tissue-selective fine-tuning of gene transcription by nuclear hormone receptors is due to different co-regulatory complexes that have various functions and enzymatic activities. Co-activator complexes include factors that contain ATP-dependent chromatin remodelling activity often associated with histone acetyltransferase (HAT) activity. Co-repressors include ATP-dependent chromatin remodelling complexes, which function as platforms for the recruitment of several subcomplexes that often contain histone deacetylase (HDAC) activity...

Miyata, K.S., McCaw, S.E., Patel, H.V., Rachubinski, R.A. Capone, J.P. (1996) The orphan nuclear hormone receptor LXR a interacts with the peroxisome proliferator-activated receptor and inhibits peroxisome proliferator signaling. J. biol. Chem., 271, 9189-9192... 

Binding to nuclear hormone receptors and either blocking or stimulation the various physiological actions that would normally occur when activated by endogenous hormones. 

---