共查询到20条相似文献,搜索用时 15 毫秒
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Structural analyses reveal phosphatidyl inositols as ligands for the NR5 orphan receptors SF-1 and LRH-1 总被引:32,自引:0,他引:32
Krylova IN Sablin EP Moore J Xu RX Waitt GM MacKay JA Juzumiene D Bynum JM Madauss K Montana V Lebedeva L Suzawa M Williams JD Williams SP Guy RK Thornton JW Fletterick RJ Willson TM Ingraham HA 《Cell》2005,120(3):343-355
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As the primary mediators of lipophilic and steroid hormone signalling, the family of nuclear receptors (NRs) plays a central role in the regulation of metazoan development. Lipophilic hormones are also thought to be important players in the molecular interaction between larval cestodes and their hosts but no member of the NR family has yet been characterised in this group of parasites. In this work, we provide for the first time evidence for the presence of NRs in cestodes of the genus Echinococcus. By bioinformatic analyses, we identified a set of 17 NRs in the genomes of E. multilocularis and E. granulosus which broadly overlapped with the set of NRs that is expressed by schistosomes, but also contained several members that are unique to cestodes. One of these receptors, EmNHR1, displayed structural homologies to the DAF-12/HR-96 subfamily of NRs that regulates cholesterol homeostasis and longevity in metazoans. By RT-PCR analyses, we demonstrate that the EmNHR1 encoding gene is expressed in all Echinococcus larval stages that are involved in the infection of the intermediate host. By yeast two-hybrid analyses, we further demonstrate cross-communication between EmNHR1 and TGF-β signalling pathways in Echinococcus and that mammalian serum contains a ligand that induces homodimerisation of the EmNHR1 ligand-binding domain. EmNHR1 could thus play an important role in hormonal host-parasite cross-communication mechanisms during an infection. On the basis of our results, further investigations into the role of NR signalling in cestode development and host-parasite interaction will be greatly facilitated. 相似文献
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Peninah M. Wairagu Kwang Hwa Park Jihye Kim Jong-Whan Choi Hyun-Won Kim Byung-Il Yeh Soon-Hee Jung Suk-Joong Yong Yangsik Jeong 《Biochemical and biophysical research communications》2014
Cancer heterogeneity is a big hurdle in achieving complete cancer treatment, which has led to the emergence of combinational therapy. In this study, we investigated the potential use of nuclear receptor (NR) ligands for combinational therapy with other anti-cancer drugs. We first profiled all 48 NRs and 48 biological anti-cancer targets in four pairs of lung cell lines, where each pair was obtained from the same patient. Two sets of cell lines were normal and the corresponding tumor cell lines while the other two sets consisted of primary versus metastatic tumor cell lines. Analysis of the expression profile revealed 11 NRs and 15 cancer targets from the two pairs of normal versus tumor cell lines, and 9 NRs and 9 cancer targets from the primary versus metastatic tumor cell lines had distinct expression patterns in each category. Finally, the evaluation of nuclear receptor ligand T0901317 for liver X receptor (LXR) demonstrated its combined therapeutic potential with tyrosine kinase inhibitors. The combined treatment of cMET inhibitor PHA665752 or EGFR inhibitor gefitinib with T0901317 showed additive growth inhibition in both H2073 and H1993 cells. Mechanistically, the combined treatment suppressed cell cycle progression by inhibiting cyclinD1 and cyclinB expression. Taken together, this study provides insight into the potential use of NR ligands in combined therapeutics with other biological anti-cancer drugs. 相似文献
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Nikolaos Volakakis Thomas Perlmann 《Biochemical and biophysical research communications》2009,390(4):1186-1191
The orphan nuclear receptor (NR) Nurr1 is expressed in the developing and adult nervous system and is also induced as an immediate early gene in a variety of cell types. In silico analysis of human promoters identified fatty acid binding protein 5 (FABP5), a protein shown to enhance retinoic acid-mediated PPARβ/δ signaling, as a potential Nurr1 target gene. Nurr1 has previously been implicated in retinoid signaling via its heterodimerization partner RXR. Since NRs are commonly involved in cross-regulatory control we decided to further investigate the regulatory relationship between Nurr1 and FABP5. FABP5 expression was up-regulated by Nurr1 and other NR4A NRs in HEK293 cells, and Nurr1 was shown to activate and bind to the FABP5 promoter, supporting that FABP5 is a direct downstream target of NR4A NRs. We also show that the RXR ligand docosahexaenoic acid (DHA) can induce nuclear translocation of FABP5. Moreover, via up-regulation of FABP5 Nurr1 can enhance retinoic acid-induced signaling of PPARβ/δ and DHA-induced activation of RXR. We also found that other members of the NR4A orphan NRs can up-regulate FABP5. Thus, our findings suggest that NR4A orphan NRs can influence signaling events of other NRs via control of FABP5 expression levels. 相似文献
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Gianpaolo RandoWalter Wahli 《生物化学与生物物理学报:疾病的分子基础》2011,1812(8):964-973
Liver metabolism is markedly sex-dimorphic; accordingly, the prevalence of liver diseases is different between sexes. The superfamily of nuclear receptors (NRs) governs the proper expression of key liver metabolism genes by sensing lipid-soluble hormones and dietary lipids. When the expression of those genes is deregulated, disease development is favored. However, we lack a comprehensive picture of the differences between NR actions in males and females. Here, we reviewed explorative studies that assessed NR functions in both sexes, and we propose a first map of sex-dimorphic NR expression in the liver. Our analysis suggested that NRs in the female liver exhibited cross-talk with more liver-protective potential than NRs in male liver. This study provides empirical support to the hypothesis that women are more resilient to some liver diseases than men, based on a more compensative NR network. This article is part of a Special Issue entitled: Translating nuclear receptors from health to disease. 相似文献
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Comparison of complete nuclear receptor sets from the human, Caenorhabditis elegans and Drosophila genomes 总被引:1,自引:0,他引:1
Maglich JM Sluder A Guan X Shi Y McKee DD Carrick K Kamdar K Willson TM Moore JT 《Genome biology》2001,2(8):research0029.1-research00297