Nuclear receptor signaling最新文献_第4页

Hairless is a nuclear receptor corepressor essential for skin function. 无毛是一种对皮肤功能至关重要的核受体辅抑制因子。

Nuclear receptor signaling Pub Date : 2009-12-31 DOI: 10.1621/nrs.07010

Catherine C Thompson

引用次数: 30

Nuclear hormone receptor architecture - form and dynamics: The 2009 FASEB Summer Conference on Dynamic Structure of the Nuclear Hormone Receptors. 核激素受体结构-形式和动态:2009年FASEB核激素受体动态结构夏季会议。

Nuclear receptor signaling Pub Date : 2009-12-31 DOI: 10.1621/nrs.07011

Iain J McEwan, Ann M Nardulli

引用次数: 9

Progesterone action in human tissues: regulation by progesterone receptor (PR) isoform expression, nuclear positioning and coregulator expression. 黄体酮在人体组织中的作用:通过黄体酮受体(PR)异构体表达、核定位和共调节因子表达进行调控。

Nuclear receptor signaling Pub Date : 2009-12-31 DOI: 10.1621/nrs.07009

Katherine M Scarpin, J Dinny Graham, Patricia A Mote, Christine L Clarke

{"title":"Progesterone action in human tissues: regulation by progesterone receptor (PR) isoform expression, nuclear positioning and coregulator expression.","authors":"Katherine M Scarpin, J Dinny Graham, Patricia A Mote, Christine L Clarke","doi":"10.1621/nrs.07009","DOIUrl":"https://doi.org/10.1621/nrs.07009","url":null,"abstract":"Progesterone is a critical regulator of normal female reproductive function, with diverse tissue-specific effects in the human. The effects of progesterone are mediated by its nuclear receptor (PR) that is expressed as two isoforms, PRA and PRB, which are virtually identical except that PRA lacks 164 amino acids that are present at the N-terminus of PRB. Considerable in vitro evidence suggests that the two PRs are functionally distinct and in animals, tissue-specific distribution patterns of PRA and PRB may account for some of the diversity of progesterone effects. In the human, PRA and PRB are equivalently expressed in most target cells, suggesting that alternative mechanisms control the diversity of progesterone actions. PR mediates the effects of progesterone by association with a range of coregulatory proteins and binding to specific target sequences in progesterone-regulated gene promoters. Ligand activation of PR results in redistribution into discrete subnuclear foci that are detectable by immunofluorescence, probably representing aggregates of multiple transcriptionally active PR-coregulator complexes. PR foci are aberrant in cancers, suggesting that the coregulator composition and number of complexes is altered. A large family of coregulators is now described and the range of proteins known to bind PR exceeds the complement required for transcriptional activation, suggesting that in the human, tissue-specific coregulator expression may modulate progesterone response. In this review, we examine the role of nuclear localization of PR, coregulator association and tissue-specific expression in modulating progesterone action in the human.","PeriodicalId":87415,"journal":{"name":"Nuclear receptor signaling","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2009-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1621/nrs.07009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28658443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 7

Erk signaling and chromatin remodeling in MMTV promoter activation by progestins. 孕激素激活MMTV启动子中的Erk信号和染色质重塑。

Nuclear receptor signaling Pub Date : 2009-10-02 DOI: 10.1621/nrs.07008

Guillermo P Vicent, Roser Zaurin, Cecilia Ballaré, A Silvina Nacht, Miguel Beato

{"title":"Erk signaling and chromatin remodeling in MMTV promoter activation by progestins.","authors":"Guillermo P Vicent, Roser Zaurin, Cecilia Ballaré, A Silvina Nacht, Miguel Beato","doi":"10.1621/nrs.07008","DOIUrl":"https://doi.org/10.1621/nrs.07008","url":null,"abstract":"Transcription from the mouse mammary tumor virus (MMTV) promoter can be induced by progestins. The progesterone receptor (PR) binds to a cluster of five hormone responsive elements (HREs) and activates the promoter by synergistic interactions with the ubiquitous transcription factor, nuclear factor 1 (NF1). Progesterone treatment of cells in culture leads to activation of the Src/Ras/Erk/Msk1 cascade. Selective inhibition of Erk, or its target kinase Msk1, interferes with chromatin remodeling and blocks MMTV activation. A complex of activated PR, Erk and Msk1 is recruited to promoter after 5 min of hormone treatment and phosphorylates histone H3 at serine 10. This modification promotes the displacement of HP1gamma and subsequent chromatin remodeling. Progestin treatment leads to the recruitment of the BAF complex, which selectively displaces histones H2A and H2B from the nucleosome containing the HREs. The acetyltransferase PCAF is also required for induction of progesterone target genes and acetylates histone H3 at K14, an epigenetic mark, which interacts with Brg1 and Brm, anchoring the BAF complex to chromatin. In nucleosomes assembled on either MMTV or mouse rDNA promoter sequences, SWI/SNF displaces histones H2A and H2B from MMTV, but not from the rDNA nucleosome. Thus, the outcome of nucleosome remodeling by purified SWI/SNF depends on DNA sequence. The resultant H3/H4 tetramer particle is then the substrate for subsequent events in induction. Thus, initial activation of the MMTV promoter requires activation of several kinases and PCAF leading to phosphoacetylation of H3, and recruitment of BAF with subsequent removal of H2A/H2B.","PeriodicalId":87415,"journal":{"name":"Nuclear receptor signaling","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2009-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1621/nrs.07008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28658442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 30

Naturally occurring C-terminal splice variants of nuclear receptors. 自然出现的核受体 C 端剪接变体。

Nuclear receptor signaling Pub Date : 2009-06-19 DOI: 10.1621/nrs.07007

Michiel van der Vaart, Marcel J M Schaaf

{"title":"Naturally occurring C-terminal splice variants of nuclear receptors.","authors":"Michiel van der Vaart, Marcel J M Schaaf","doi":"10.1621/nrs.07007","DOIUrl":"10.1621/nrs.07007","url":null,"abstract":"Alternative mRNA splicing in the region encoding the C-terminus of nuclear receptors results in receptor variants lacking the entire ligand-binding domain (LBD), or a part of it, and instead contain a sequence of splice variant-specific C-terminal amino acids. A total of thirteen such splice variants have been shown to occur in vertebrates, and at least nine occur in humans. None of these receptor variants appear to be able to bind endogenous ligands and to induce transcription on promoters containing the response element for the respective canonical receptor variant. Interestingly, ten of these C-terminal splice variants have been shown to display dominant-negative activity on the transactivational properties of their canonical equivalent. Research on most of these splice variants has been limited, and the dominant-negative effect of these receptor variants has only been demonstrated in reporter assays in vitro, using transiently transfected receptors and reporter constructs. Therefore, the in vivo function and relevance of most C-terminal splice variants remains unclear. By reviewing the literature on the human glucocorticoid receptor beta-isoform (hGRbeta), we show that the dominant-negative effect of hGRbeta is well established using more physiologically relevant readouts. The hGR beta-isoform may alter gene transcription independent from the canonical receptor and increased hGRbeta levels correlate with glucocorticoid resistance and the occurrence of several immune-related diseases. Thus, available data suggests that C-terminal splice variants of nuclear receptors act as dominant-negative inhibitors of receptor-mediated signaling in vivo, and that aberrant expression of these isoforms may be involved in the pathogenesis of a variety of diseases.","PeriodicalId":87415,"journal":{"name":"Nuclear receptor signaling","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2009-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2716050/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28332841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Developmental expression of retinoic acid receptors (RARs). 视黄酸受体(RARs)的发育表达。

Nuclear receptor signaling Pub Date : 2009-05-12 DOI: 10.1621/nrs.07006

Pascal Dollé

{"title":"Developmental expression of retinoic acid receptors (RARs).","authors":"Pascal Dollé","doi":"10.1621/nrs.07006","DOIUrl":"https://doi.org/10.1621/nrs.07006","url":null,"abstract":"Here, I review the developmental expression features of genes encoding the retinoic acid receptors (RARs) and the 'retinoid X' or rexinoid receptors (RXRs). The first detailed expression studies were performed in the mouse over two decades ago, following the cloning of the murine Rar genes. These studies revealed complex expression features at all stages of post-implantation development, one receptor gene (Rara) showing widespread expression, the two others (Rarb and Rarg) with highly regionalized and/or cell type-specific expression in both neural and non-neural tissues. Rxr genes also have either widespread (Rxra, Rxrb), or highly-restricted (Rxrg) expression patterns. Studies performed in zebrafish and Xenopus demonstrated expression of Rar and Rxr genes (both maternal and zygotic), at early pre-gastrulation stages. The eventual characterization of specific enzymes involved in the synthesis of retinoic acid (retinol/retinaldehyde dehydrogenases), or the triggering of its catabolism (CYP26 cytochrome P450s), all of them showing differential expression patterns, led to a clearer understanding of the phenomenons regulated by retinoic acid signaling during development. Functional studies involving targeted gene disruptions in the mouse, and additional approaches such as dominant negative receptor expression in other models, have pinpointed the specific, versus partly redundant, roles of the RARs and RXRs in many developing organ systems. These pleiotropic roles are summarized hereafter in relationship to the receptors' expression patterns.","PeriodicalId":87415,"journal":{"name":"Nuclear receptor signaling","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2009-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1621/nrs.07006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28199161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 137

A novel approach to investigate the subcellular distribution of nuclear receptors in vivo. 研究体内核受体亚细胞分布的新方法。

Nuclear receptor signaling Pub Date : 2009-05-08 DOI: 10.1621/nrs.07004

Marko Matic, Sarah Nakhel, Anne M Lehnert, Patsie Polly, Stephen J Clarke, Graham R Robertson

{"title":"A novel approach to investigate the subcellular distribution of nuclear receptors in vivo.","authors":"Marko Matic, Sarah Nakhel, Anne M Lehnert, Patsie Polly, Stephen J Clarke, Graham R Robertson","doi":"10.1621/nrs.07004","DOIUrl":"https://doi.org/10.1621/nrs.07004","url":null,"abstract":"Subcellular compartmentalisation and the intracellular movement of nuclear receptors are major regulatory steps in executing their transcriptional function. Though significant progress has been made in understanding these regulatory processes in cultured mammalian cells, such results have rarely been confirmed within cells of a living mammal. This article describes a simple, time-efficient approach to study the nuclear versus cytoplasmic accumulation of nuclear receptors and the regions of nuclear receptor proteins that govern subcellular trafficking within hepatocytes of live mice. Pregnane X receptor, a xenobiotic-activated member of the nuclear receptor family, was used to exemplify the approach. Using dual-labeled wild-type and mutant PXR expression constructs, we outline their in vivo delivery, simultaneous cellular expression, visualization and categorical classification within hepatocytes of live mice. Using this approach, we identified three mutants that had an altered subcellular distribution in the presence and absence of a PXR ligand. This novel in vivo method complements the current cell culture-based experimental systems in protein subcellular localisation studies.","PeriodicalId":87415,"journal":{"name":"Nuclear receptor signaling","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2009-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1621/nrs.07004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28199159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Dynamic and combinatorial control of gene expression by nuclear retinoic acid receptors (RARs). 核视黄酸受体（RARs）对基因表达的动态和组合控制。

Nuclear receptor signaling Pub Date : 2009-05-08 DOI: 10.1621/nrs.07005

Cécile Rochette-Egly, Pierre Germain

引用次数: 0

Function of retinoic acid receptors during embryonic development. 视黄酸受体在胚胎发育中的功能。

Nuclear receptor signaling Pub Date : 2009-01-01 Epub Date: 2009-04-03 DOI: 10.1621/nrs.07002

Manuel Mark, Norbert B Ghyselinck, Pierre Chambon

{"title":"Function of retinoic acid receptors during embryonic development.","authors":"Manuel Mark, Norbert B Ghyselinck, Pierre Chambon","doi":"10.1621/nrs.07002","DOIUrl":"https://doi.org/10.1621/nrs.07002","url":null,"abstract":"Retinoids, the active metabolites of vitamin A, regulate complex gene networks involved in vertebrate morphogenesis, growth, cellular differentiation and homeostasis. Studies performed in vitro, using either acellular systems or transfected cells, have shown that retinoid actions are mediated through heterodimers between the RAR and RXR nuclear receptors. However, in vitro studies indicate what is possible, but not necessarily what is actually occurring in vivo, because they are performed under non-physiological conditions. Therefore, genetic approaches in the animal have been be used to determine the physiological functions of retinoid receptors. Homologous recombination in embryonic stem cells has been used to generate germline null mutations of the RAR- and RXR-coding genes in the mouse. As reviewed here, the generation of such germline mutations, combined with pharmacological approaches to block the RA signalling pathway, has provided genetic evidence that RAR/RXR heterodimers are indeed the functional units transducing the RA signal during prenatal development. However, due to (i) the complexity in \"hormonal\" signalling through transduction by the multiple RARs and RXRs, (ii) the functional redundancies (possibly artefactually generated by the mutations) within receptor isotypes belonging to a given family, and (iii) in utero or early postnatal lethality of certain germline null mutations, these genetic studies have failed to reveal all the physiological functions of RARs and RXRs, notably in adults. Spatio-temporally-controlled somatic mutations generated in given cell types/tissues and at chosen times during postnatal life, will be required to reveal all the functions of RAR and RXR throughout the lifetime of the mouse.","PeriodicalId":87415,"journal":{"name":"Nuclear receptor signaling","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1621/nrs.07002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28195441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 73

The steroid and xenobiotic receptor (SXR), beyond xenobiotic metabolism. 类固醇和异种受体(SXR)，超越异种代谢。

Nuclear receptor signaling Pub Date : 2009-01-01 Epub Date: 2009-01-16 DOI: 10.1621/nrs.07001

Changcheng Zhou, Suman Verma, Bruce Blumberg

{"title":"The steroid and xenobiotic receptor (SXR), beyond xenobiotic metabolism.","authors":"Changcheng Zhou, Suman Verma, Bruce Blumberg","doi":"10.1621/nrs.07001","DOIUrl":"https://doi.org/10.1621/nrs.07001","url":null,"abstract":"The steroid and xenobiotic receptor (SXR) (also known as pregnane X receptor or PXR) is a nuclear hormone receptor activated by a diverse array of endogenous hormones, dietary steroids, pharmaceutical agents, and xenobiotic compounds. SXR has an enlarged, flexible, hydrophobic ligand binding domain (LBD) which is remarkably divergent across mammalian species and SXR exhibits considerable differences in its pharmacology among mammals. The broad response profile of SXR has led to the development of \"the steroid and xenobiotic sensor hypothesis\". SXR has been established as a xenobiotic sensor that coordinately regulates xenobiotic clearance in the liver and intestine via induction of genes involved in drug and xenobiotic metabolism. In the past few years, research has revealed new and mostly unsuspected roles for SXR in modulating inflammation, bone homeostasis, vitamin D metabolism, lipid homeostasis, energy homeostasis and cancer. The identification of SXR as a xenobiotic sensor has provided an important tool for studying new mechanisms through which diet, chemical exposure, and environment ultimately impact health and disease. The discovery and pharmacological development of new PXR modulators might represent an interesting and innovative therapeutic approach to combat various diseases.","PeriodicalId":87415,"journal":{"name":"Nuclear receptor signaling","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1621/nrs.07001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28004556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 168