Retinoic Acid Actions through Mammalian Nuclear Receptors

Metabolic Signaling and Disease Program, Sanford-Burnham Medical Research Institute , Orlando, Florida 32827, United States.
Chemical Reviews (Impact Factor: 45.66). 12/2013; 114(1). DOI: 10.1021/cr400161b
Source: PubMed
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    ABSTRACT: An easy and simple synthesis route has been developed to prepare FeNi carbon microspheres with large pore sizes. The adsorption of tretinoin onto the obtained FeNi carbon microspheres is investigated. Experimental results showed that FeNi nanoparticles were favorable for the formation of crystalline graphitic carbon, with low crystallinity. The adsorption behavior of tretinoin was well correlated with time and could be described using a simple equation. Values for the relevant fitting parameters were obtained, and the physical meanings of the parameters were defined.
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    ABSTRACT: Nuclear receptors (NRs), a family of 48 transcriptional factors, have been studied intensively for their roles in cancer development and progression. The presence of distinctive ligand binding sites capable of interacting with small molecules has made NRs attractive targets for developing cancer therapeutics. In particular, a number of drugs have been developed over the years to target human androgen- and estrogen receptors for the treatment of prostate cancer and breast cancer. In contrast, orphan nuclear receptors (ONRs), which in many cases lack known biological functions or ligands, are still largely under investigated. This review is a summary on ONRs that have been implicated in prostate and breast cancers, specifically retinoic acid-receptor-related orphan receptors (RORs), liver X receptors (LXRs), chicken ovalbumin upstream promoter transcription factors (COUP-TFs), estrogen related receptors (ERRs), nerve growth factor 1B-like receptors, and "dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1" (DAX1). Discovery and development of small molecules that can bind at various functional sites on these ONRs will help determine their biological functions. In addition, these molecules have the potential to act as prototypes for future drug development. Ultimately, the therapeutic value of targeting the ONRs may go well beyond prostate and breast cancers.
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    ABSTRACT: The crystal structures of three nuclear receptor (NR) complexes have emerged to reveal their multidomain architectures on DNA. These pictures provide unprecedented views of interfacial couplings between the DNA-binding domains (DBDs) and ligand-binding domains (LBDs). The detailed pictures contrast with previous interpretations of low-resolution electron microscopy (EM) and small angle X-ray scattering (SAXS) data, which had suggested a common architecture with noninteracting DBDs and LBDs. Revisiting both historical and recent interpretations of NR architecture, we invoke new principles underlying higher-order quaternary organization and the allosteric transmission of signals between domains. We also discuss how NR architectures are being probed in living cells to understand dimerization and DNA-binding events in real time. Copyright © 2014 Elsevier Ltd. All rights reserved.
    Trends in Biochemical Sciences 11/2014; 40(1). DOI:10.1016/j.tibs.2014.10.011 · 13.52 Impact Factor


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