Nuclear receptor signaling最新文献_第9页

Oncogenic conversion of the thyroid hormone receptor by altered nuclear transport. 甲状腺激素受体通过改变核转运的致癌性转化。

Nuclear receptor signaling Pub Date : 2006-01-01 Epub Date: 2006-04-28 DOI: 10.1621/nrs.04008

Ghislain M C Bonamy, Lizabeth A Allison

{"title":"Oncogenic conversion of the thyroid hormone receptor by altered nuclear transport.","authors":"Ghislain M C Bonamy, Lizabeth A Allison","doi":"10.1621/nrs.04008","DOIUrl":"https://doi.org/10.1621/nrs.04008","url":null,"abstract":"Nuclear receptors (NRs) are transcription factors whose activity is modulated by ligand binding. These receptors are at the core of complex signaling pathways and act as integrators of many cellular signals. In the last decade our understanding of NRs has greatly evolved. In particular, regulation of NR subcellular dynamics has emerged as central to their activity. Research on the subcellular distribution of the thyroid hormone receptor (TR) has revealed new dimensions in the complexity of NR regulation, and points to the possibility that NR mislocalization plays a key role in oncogenesis. For many years, TR was thought to reside exclusively in the nucleus. It is now known that TR is a dynamic protein that shuttles between the nucleus and cytoplasm. TR is localized to the nucleus in a phosphorylated form, suggesting that compartment-specific phosphorylation mediates cross-talk between multiple cell signaling pathways. The oncoprotein v-ErbA, a viral-derived dominant negative variant of TR is actively exported to the cytoplasm by the CRM1 export receptor. Strikingly, the oncoprotein causes mislocalization of cellular TR and some of its coactivators by direct interaction. Here, we offer some perspectives on the role of subcellular trafficking in the oncogenic conversion of TR, and propose a new model for oncoprotein dominant negative activity.","PeriodicalId":87415,"journal":{"name":"Nuclear receptor signaling","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1621/nrs.04008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26061360","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: 62

Zimp7 and Zimp10, two novel PIAS-like proteins, function as androgen receptor coregulators. Zimp7和Zimp10是两个新的pnas样蛋白，具有雄激素受体共调节因子的功能。

Nuclear receptor signaling Pub Date : 2006-01-01 Epub Date: 2006-07-07 DOI: 10.1621/nrs.04017

Jason Beliakoff, Zijie Sun

{"title":"Zimp7 and Zimp10, two novel PIAS-like proteins, function as androgen receptor coregulators.","authors":"Jason Beliakoff, Zijie Sun","doi":"10.1621/nrs.04017","DOIUrl":"https://doi.org/10.1621/nrs.04017","url":null,"abstract":"The androgen receptor (AR) plays a critical role in male sexual development and in normal and malignant prostate cell growth and survival. It has been shown that AR transcriptional activation is regulated through interactions with a variety of transcriptional co-regulators. The Protein Inhibitors of Activated STATs (PIAS) are transcriptional co-regulators, and have been shown to modulate AR-mediated transcription. In this brief, we summarize our recent studies on two novel PIAS-like proteins, Zimp7 and Zimp10. Particularly, we address the functional interactions between the AR and these two proteins, and potential mechanisms by which they regulate AR mediated transcription. In addition, we explore potential roles of Zimp10 in transcriptional regulation in vivo using a recent Zimp10 knockout mouse model. Taken together, our findings thus far suggest that Zimp7 and Zimp10 are functionally non-redundant and share unique characteristics that have not been described for the PIAS family. Further investigation into the functional roles of these two PIAS-like proteins may help to better understand prostate cancer progression, and yield possible new targets for therapeutic intervention.","PeriodicalId":87415,"journal":{"name":"Nuclear receptor signaling","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1621/nrs.04017","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26160491","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: 32

Thyroid hormone mediated changes in gene expression can be initiated by cytosolic action of the thyroid hormone receptor beta through the phosphatidylinositol 3-kinase pathway. 甲状腺激素介导的基因表达变化可通过磷脂酰肌醇3激酶途径由甲状腺激素受体β的胞质作用启动。

Nuclear receptor signaling Pub Date : 2006-01-01 Epub Date: 2006-07-07 DOI: 10.1621/nrs.04020

Lars C Moeller, Xia Cao, Alexandra M Dumitrescu, Hisao Seo, Samuel Refetoff

{"title":"Thyroid hormone mediated changes in gene expression can be initiated by cytosolic action of the thyroid hormone receptor beta through the phosphatidylinositol 3-kinase pathway.","authors":"Lars C Moeller, Xia Cao, Alexandra M Dumitrescu, Hisao Seo, Samuel Refetoff","doi":"10.1621/nrs.04020","DOIUrl":"https://doi.org/10.1621/nrs.04020","url":null,"abstract":"Thyroid hormone (TH) action is mediated principally through binding of the hormone ligand, 3,3,5-triiodothyronine (T3), to TH receptors (TRs). This hormone-receptor interaction recruits other proteins to form complexes that regulate gene expression by binding to DNA sequences in the promoter of target genes. We recently described an extranuclear mechanism of TH action that consists of the association of TH-liganded TRbeta with p85alpha [regulatory subunit of phosphatidylinositol 3-kinase (PI3K)] in the cytosol and subsequent activation of the PI3K, generating phosphatidylinositol 3,4,5-triphosphate [PtdIns(3,4,5)P3]. This initiates the activation of a signaling cascade by phosphorylation of Akt, mammalian target of rapamycin (mTOR) and its substrate p70(S6K), leading to the stimulation of ZAKI-4alpha synthesis, a calcineurin inhibitor. Furthermore, we found that this same mechanism leads to induction of the transcription factor hypoxia-inducible factor (HIF-1alpha), and its target genes, glucose transporter (GLUT)1, platelet-type phosphofructokinase (PFKP), and monocarboxylate transporter (MCT) 4. These genes are of special interest, because their products have important roles in cellular glucose metabolism, from glucose uptake (GLUT1) to glycolysis (PFKP) and lactate export (MCT4). These results demonstrate that the TH-TRbeta complex can exert a non-genomic action in the cytosol leading to changes in gene expression by direct (HIF-1alpha) and indirect (ZAKI-4alpha, GLUT1, PFKP) means.","PeriodicalId":87415,"journal":{"name":"Nuclear receptor signaling","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1621/nrs.04020","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26160947","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

Ligand-induced estrogen receptor alpha degradation by the proteasome: new actors? 配体诱导的蛋白酶体雌激素受体α降解:新的参与者?

Nuclear receptor signaling Pub Date : 2006-01-01 Epub Date: 2006-02-08 DOI: 10.1621/nrs.04004

Mathilde Calligé, Hélène Richard-Foy

引用次数: 41

Application of phosphorylation site-specific antibodies to measure nuclear receptor signaling: characterization of novel phosphoantibodies for estrogen receptor alpha. 应用磷酸化位点特异性抗体测量核受体信号:雌激素受体α的新型磷酸化抗体的表征。

Nuclear receptor signaling Pub Date : 2006-01-01 Epub Date: 2006-04-28 DOI: 10.1621/nrs.04007

Mariam H Al-Dhaheri, Brian G Rowan

引用次数: 32

Hic-5, an adaptor-like nuclear receptor coactivator. Hic-5，一种类似适配器的核受体辅激活剂。

Nuclear receptor signaling Pub Date : 2006-01-01 Epub Date: 2006-07-07 DOI: 10.1621/nrs.04019

Marjet D Heitzer, Donald B DeFranco

引用次数: 17

The NR4A subgroup: immediate early response genes with pleiotropic physiological roles. NR4A亚群:具有多效生理作用的即时早期反应基因。

Nuclear receptor signaling Pub Date : 2006-01-01 Epub Date: 2006-02-08 DOI: 10.1621/nrs.04002

Megan A Maxwell, George E O Muscat

{"title":"The NR4A subgroup: immediate early response genes with pleiotropic physiological roles.","authors":"Megan A Maxwell, George E O Muscat","doi":"10.1621/nrs.04002","DOIUrl":"https://doi.org/10.1621/nrs.04002","url":null,"abstract":"The nuclear hormone receptor (NR) superfamily includes the orphan NR4A subgroup, comprised of Nur77 (NR4A1), Nurr1 (NR4A2) and NOR-1 (NR4A3). These NRs are classified as early response genes, are induced by a diverse range of signals, including fatty acids, stress, growth factors, cytokines, peptide hormones, phorbol esters, neurotransmitters, and physical stimuli (for example magnetic fields, shear stress). The ability to sense and rapidly respond to changes in the cellular environment thus appears to be a hallmark of this subfamily. The members of the NR4A subgroup are well conserved in the DNA binding domain (approximately 91-95%) and the C-terminal ligand-binding domain (approximately 60%), but are divergent in the N-terminal AB region. These receptors bind as monomers, homodimers and heterodimers with RXRs (to mediate retinoid signaling) to different permutations of the canonical NR binding motif. The NR4A subgroup activates gene expression in a constitutive ligand-independent manner. NR4A-mediated trans-activation (LBD) involves unusually active N-terminal AF-1 domains that mediate coactivator recruitment. Moreover, the NR4A receptors encode atypical LBDs and AF-2 domains. For example, the LBDs contain no cavity due to bulky hydrophobic residue side chains, and lack the classical coactivator-binding cleft constituted by helices 3, 4 and 12. However, a hydrophobic patch exists between helices 11 and 12, that encodes a novel cofactor interface that modulates transcriptional activity. In line with the pleiotropic physiological stimuli that induce the NR4A subgroup, these orphan NRs have been implicated in cell cycle regulation (and apoptosis), neurological disease, steroidogenesis, inflammation, carcinogenesis and atherogenesis.","PeriodicalId":87415,"journal":{"name":"Nuclear receptor signaling","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1621/nrs.04002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25964260","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: 403

Single-step purification of full-length human androgen receptor. 人雄激素受体全长单步纯化。

Nuclear receptor signaling Pub Date : 2005-01-01 Epub Date: 2005-10-21 DOI: 10.1621/nrs.03001

Dalia Juzumiene, Ching-yi Chang, Daju Fan, Tanya Hartney, John D Norris, Donald P McDonnell

引用次数: 17

Detection of designer steroids. 设计类固醇的检测。

Nuclear receptor signaling Pub Date : 2005-01-01 Epub Date: 2005-10-21 DOI: 10.1621/nrs.03002

Xiaohui Yuan, Barry Marc Forman

引用次数: 13

Corepressors: custom tailoring and alterations while you wait. 协阻遏器:定制剪裁和改变，而你等待。

Nuclear receptor signaling Pub Date : 2005-01-01 Epub Date: 2005-10-21 DOI: 10.1621/nrs.03003

Michael Goodson, Brian A Jonas, Martin A Privalsky

{"title":"Corepressors: custom tailoring and alterations while you wait.","authors":"Michael Goodson, Brian A Jonas, Martin A Privalsky","doi":"10.1621/nrs.03003","DOIUrl":"https://doi.org/10.1621/nrs.03003","url":null,"abstract":"A diverse cadre of metazoan transcription factors mediate repression by recruiting protein complexes containing the SMRT (silencing mediator of retinoid and thyroid hormone receptor) or N-CoR (nuclear receptor corepressor) corepressors. SMRT and N-CoR nucleate the assembly of still larger corepressor complexes that perform the specific molecular incantations necessary to confer transcriptional repression. Although SMRT and N-CoR are paralogs and possess similar molecular architectures and mechanistic strategies, they nonetheless exhibit distinct molecular and biological properties. It is now clear that the functions of both SMRT and N-CoR are further diversified through alternative mRNA splicing, yielding a series of corepressor protein variants that participate in distinctive transcription factor partnerships and display distinguishable repression properties. This review will discuss what is known about the structure and actions of SMRT, N-CoR, and their splicing variants, and how alternative splicing may allow the functions of these corepressors to be adapted and tailored to different cells and to different developmental stages.","PeriodicalId":87415,"journal":{"name":"Nuclear receptor signaling","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2005-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1621/nrs.03003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25964266","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: 72