Nuclear receptor signaling最新文献

Glucocorticoid receptor (GR) and related steroid hormone receptors are ligand-dependent transcription factors whose regulation is critical for both homeostasis and diseases. The structural maturation of the GR has been shown to require the Hsp90 molecular chaperone complex. Evidence indicates that Hsp90-dependent maturation is critical for GR ligand binding capacity and activity. While the role for Hsp90 in GR function is well established, the regulation of this process is not well understood. Here we discuss a recent finding that identifies reversible protein acetylation controlled by the deacetylase HDAC6 as a novel mechanism that regulates Hsp90-dependent GR maturation. We will also speculate on the implications of this finding in steroid hormone signaling, oncogenic transformation and its potential therapeutic utility.

Deposition of the beta-amyloid (Abeta) peptide is thought to underlie development of Alzheimer's disease (AD). This pathological linkage has spurred considerable interest in therapeutic strategies to reduce Abeta production. It is becoming increasingly clear that altered cholesterol homeostasis can modulate Abeta production and/or accumulation. In this review, we discuss the molecular pathology of AD, the cholesterol connection and recent data suggesting that the oxysterol receptor, liver X receptor LXR (NR1H2 and NR1H3), may modulate these events.

The ability of NR LBDs to transfer repression function to a heterologous DNA binding domain, and the cross-squelching of repression by untethered LBDs, has suggested that repression is mediated by interactions with putative cellular corepressor proteins. The yeast-two hybrid screen for protein interactors has proven to be the key to the isolation and characterization of corepressors. This short review will focus on N-CoR and SMRT.

The effects of estrogen are mediated through two functionally distinct receptors, estrogen receptor alpha (ER- alpha ), and estrogen receptor beta (ER- beta ), both of which are expressed in the cardiovascular system. The etiology of cardiovascular disease is believed to result in part from the loss of endogenous estrogen, indicating that estrogen and its receptors may play important roles in the prevention of cardiovascular disease in women.

A major goal of the Nuclear Receptor Signaling Atlas (NURSA) is to elucidate the biochemical and physiological roles of nuclear receptors in vivo. Characterizing the tissue expression pattern of individual receptors and their target genes in whole animals under various pharmacological conditions and genotypes is an essential component of this aim. Here we describe a high-throughput quantitative, real-time, reverse-transcription PCR (QPCR) method for the measurement of both the relative level of expression of a particular transcript in a given tissue or cell type, and the relative change in expression of a particular transcript after pharmacologic or genotypic manipulation. This method is provided as a standardized protocol for those in the nuclear receptor field. It is meant to be a simplified, easy to use protocol for the rapid, high-throughput measurement of transcript levels in a large number of samples. A subsequent report will provide validated primer and probe sequence information for the entire mouse and human nuclear receptor superfamily.

Atherosclerosis is a chronic disease of the arteries whose development involves a local inflammatory response characterized by the activation of different cells such as macrophages, T-lymphocytes, smooth muscle cells (SMCs) and endothelial cells (ECs). This review will summarize recent evidence for a modulatory role of the nuclear receptor ROR-alpha in cardiovascular disease.

Nuclear receptors comprise a superfamily of sequence-specific transcription factors whose members have diverse roles during development. This review will summarize the developmental roles of selected members of the nuclear receptor superfamily.

A series of data has accumulated over the past five years that raises questions about our current understanding of the transcriptional process and its regulation. Following the discovery of coactivators for nuclear receptors (NRs), a large number of these molecules have been reported in the literature. This perspective will summarize some opinions on the significance of this large number of factors.

Nuclear receptors are DNA-binding transcription factors, the transcriptional function of many of which depends on the binding of ligands, a feature that distinguishes nuclear receptors from other transcription factors. This review will summarize recent advances in our knowledge of the interaction between selected nuclear receptors and their cognate ligands.

The long term goal of the Nuclear Receptor Signaling Atlas (NURSA) resides in unraveling the physiological and pathological functions of nuclear receptors (NRs) at the molecular, biochemical and cellular levels. This multi-oriented task requires complementary approaches in order to determine the specific function(s) and precise expression and receptor activity patterns for each individual conventional or orphan receptor. To attain this objective, we have chose to turn to technologies recently made available to engineer bacterial artificial chromosomes (BACs).