Ordóñez-Morán Paloma, Muñoz Alberto
Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Madrid, Spain
Cell Cycle. 2009 Jun 1;8(11):1675-80. doi: 10.4161/cc.8.11.8579.
The nuclear receptor superfamily mediates the regulatory activities of many hormones, nutrients and metabolites on the homeostasis and physiology of cells and tissues. Classically, ligand binding induced the ability of nuclear receptors to modulate the transcription rate of target genes (genomic effects), which led to consider them as ligand-activated transcription factors. Later, rapid actions of nuclear receptor ligands were reported that did not involve changes in gene expression. These (non-genomic) effects have been attributed in some cases to receptors different to those mediating gene transcription but most evidences indicate that they result from the activity of a population of nuclear receptor molecules acting outside the cell nucleus. Recent studies on estrogen and vitamin D, and their receptors (ERalpha/beta, VDR) support now the idea that non-genomic and genomic effects may integrate in a unique mode of action of nuclear receptor ligands, in which the non-genomic effects constitute signaling pathways required for the effects at the genome level. Here, we will discuss these novel findings and also those indicating transcriptional regulation through ligand-dependent and -independent crosstalk of nuclear receptors with beta-catenin or VDR-interacting repressor (VDIR).
核受体超家族介导许多激素、营养物质和代谢产物对细胞和组织的稳态及生理学的调节作用。传统上，配体结合诱导核受体调节靶基因转录速率的能力（基因组效应），这使得它们被视为配体激活的转录因子。后来，有报道称核受体配体具有不涉及基因表达变化的快速作用。在某些情况下，这些（非基因组）效应被归因于与介导基因转录的受体不同的受体，但大多数证据表明它们是由一群在细胞核外发挥作用的核受体分子的活性导致的。最近关于雌激素和维生素D及其受体（ERα/β、VDR）的研究现在支持这样一种观点，即非基因组效应和基因组效应可能以核受体配体的独特作用模式整合，其中非基因组效应构成基因组水平效应所需的信号通路。在这里，我们将讨论这些新发现，以及那些表明通过核受体与β-连环蛋白或VDR相互作用阻遏物（VDIR）的配体依赖性和非依赖性相互作用进行转录调控的发现。
