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Steroid receptor coactivator

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https://www.readbyqxmd.com/read/28890360/synergistic-regulation-of-coregulator-nuclear-receptor-interaction-by-ligand-and-dna
#1
Ian Mitchelle S de Vera, Jie Zheng, Scott Novick, Jinsai Shang, Travis S Hughes, Richard Brust, Paola Munoz-Tello, William J Gardner, David P Marciano, Xiangming Kong, Patrick R Griffin, Douglas J Kojetin
Nuclear receptor (NR) transcription factors bind various coreceptors, small-molecule ligands, DNA response element sequences, and transcriptional coregulator proteins to affect gene transcription. Small-molecule ligands and DNA are known to influence receptor structure, coregulator protein interaction, and function; however, little is known on the mechanism of synergy between ligand and DNA. Using quantitative biochemical, biophysical, and solution structural methods, including (13)C-detected nuclear magnetic resonance and hydrogen/deuterium exchange (HDX) mass spectrometry, we show that ligand and DNA cooperatively recruit the intrinsically disordered steroid receptor coactivator-2 (SRC-2/TIF2/GRIP1/NCoA-2) receptor interaction domain to peroxisome proliferator-activated receptor gamma-retinoid X receptor alpha (PPARγ-RXRα) heterodimer and reveal the binding determinants of the complex...
August 23, 2017: Structure
https://www.readbyqxmd.com/read/28844863/structural-and-functional-impacts-of-er-coactivator-sequential-recruitment
#2
Ping Yi, Zhao Wang, Qin Feng, Chao-Kai Chou, Grigore D Pintilie, Hong Shen, Charles E Foulds, Guizhen Fan, Irina Serysheva, Steven J Ludtke, Michael F Schmid, Mien-Chie Hung, Wah Chiu, Bert W O'Malley
Nuclear receptors recruit multiple coactivators sequentially to activate transcription. This "ordered" recruitment allows different coactivator activities to engage the nuclear receptor complex at different steps of transcription. Estrogen receptor (ER) recruits steroid receptor coactivator-3 (SRC-3) primary coactivator and secondary coactivators, p300/CBP and CARM1. CARM1 recruitment lags behind the binding of SRC-3 and p300 to ER. Combining cryo-electron microscopy (cryo-EM) structure analysis and biochemical approaches, we demonstrate that there is a close crosstalk between early- and late-recruited coactivators...
September 7, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28826365/src-3-plays-a-critical-role-in-human-umbilical-vein-endothelial-cells-by-regulating-the-pi3k-akt-mtor-pathway-in-preeclampsia
#3
Yu Yuan, Nan Shan, Bin Tan, Qinyin Deng, Yangming Liu, Hanbin Wang, Xiaofang Luo, Chengjin He, Xin Luo, Hua Zhang, Philip N Baker, David M Olson, Hongbo Qi
Preeclampsia (PE) is currently thought to be characterized by oxidative stress which may lead to endothelial dysfunction. The normal function of vascular endothelium is essential to vascular homeostasis. Previous studies have shown that steroid receptor coactivator 3 (SRC-3) interacts with estrogen receptors (ERs) which are involved in the vasoprotective effects of estrogen and is also associated with cell migration, invasion, and inflammation; however, its role in PE remains unclear. The main purpose of this study is to identify the role of SRC-3 in the function of human umbilical vein endothelial cells (HUVECs) during the development of PE...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28816099/sex-differences-of-steroid-receptor-coactivator-1-expression-after-spinal-cord-injury-in-mice
#4
Jiayu Xiao, Jiqiang Zhang, Yangang Zhao, Wenjie Huang, Zhikai Guo, Bingyin Su, Qiang Guo
OBJECTIVE: The neural functional recovery of female is often better than that of male after spinal cord injury (SCI). Evidences show that estrogen can attenuate inflammation and promote the neural survival and regeneration after SCI. SRC-1 is an essential initiation factor for the estrogen-regulated target gene transcription and plays a key role in regulating estrogen activity. However, it is not known whether and how SRC-1 mediates the neural regeneration promoted by estrogen after SCI...
August 17, 2017: Neurological Research
https://www.readbyqxmd.com/read/28768874/pgc1%C3%AE-transcriptional-adaptor-function-governs-hepatitis-b-virus-replication-by-controlling-hbcag-p21-protein-mediated-capsid-formation
#5
Rasha E Shalaby, Saira Iram, Bülent Çakal, Claudia E Oropeza, Alan McLachlan
In the human hepatoma cell line, Huh7, co-expression of the coactivators, peroxisome proliferator-activated receptor gamma coactivator 1α (PGC1α), cAMP responsive element binding protein binding protein (CBP), steroid receptor coactivator 1 (SRC1) and protein arginine methyltransferase 1 (PRMT1) only modestly increase HBV biosynthesis. However, utilizing the human embryonic kidney cell line, HEK293T, it was possible to demonstrate that PGC1α alone can support viral biosynthesis independently of additional coactivator or transcription factor expression...
August 2, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28674826/conifer-diterpene-resin-acids-disrupt-juvenile-hormone-mediated-endocrine-regulation-in-the-indian-meal-moth-plodia-interpunctella
#6
Hyun-Woo Oh, Chan-Seok Yun, Jun Hyoung Jeon, Ji-Ae Kim, Doo-Sang Park, Hyung Won Ryu, Sei-Ryang Oh, Hyuk-Hwan Song, Yunhee Shin, Chan Sik Jung, Sang Woon Shin
Diterpene resin acids (DRAs) are important components of oleoresin and greatly contribute to the defense strategies of conifers against herbivorous insects. In the present study, we determined that DRAs function as insect juvenile hormone (JH) antagonists that interfere with the juvenile hormone-mediated binding of the JH receptor Methoprene-tolerant (Met) and steroid receptor coactivator (SRC). Using a yeast two-hybrid system transformed with Met and SRC from the Indian meal moth Plodia interpunctella, we tested the interfering activity of 3704 plant extracts against JH III-mediated Met-SRC binding...
July 3, 2017: Journal of Chemical Ecology
https://www.readbyqxmd.com/read/28645579/anti-androgenic-mechanisms-of-bisphenol-a-involve-androgen-receptor-signaling-pathway
#7
Hui Wang, Zhen Ding, Qiao-Mei Shi, Xing Ge, Heng-Xue Wang, Meng-Xue Li, Gang Chen, Qi Wang, Qiang Ju, Jin-Peng Zhang, Mei-Rong Zhang, Li-Chun Xu
We have shown Bisphenol A (BPA) acts as an androgen receptor (AR) antagonist in the previous study. However, the mechanisms underlying anti-androgenic effects of BPA remain unclear. The objective of this study was to explore whether the AR signaling was involved in AR antagonism of BPA. The Cell Counting Kit-8 (CCK-8) assay and Real-Time Cell Analysis (RTCA) iCELLigence system were applied to analyze the mouse Sertoli cell TM4 proliferation. The mammalian two-hybrid assays were performed to investigate the effects of BPA on the AR amino- and carboxyl-terminal regions (N/C) interaction and the interactions of the AR with steroid receptor coactivator-1 (SRC-1), co-repressors including silencing mediator for thyroid hormone receptors (SMRT) and nuclear receptor co-repressor (NCoR)...
July 15, 2017: Toxicology
https://www.readbyqxmd.com/read/28645352/r%C3%A3-sistances-aux-hormones-st%C3%A3-ro%C3%A3-des-physiologie-et-pathologie-pathophysiology-of-steroid-resistance-syndrome
#8
N Ramos, M Lombès
Steroid resistance syndrome (mineralocorticoids, glucocorticoids, estrogens, androgens) is a rare clinical disorder, androgen insensitivity syndrome being the most commonly described. Resistance syndromes are characterized by elevated steroid hormone levels, secondary to an impaired signal transduction and a lack of negative feedback, without any specific clinical signs of steroid excess. In most cases, steroid hormone resistance is generally caused by steroid receptor mutations. Several nonsense and missense mutations or deletions have already been described for all steroid receptors, except for the progesterone receptor...
October 2016: Annales D'endocrinologie
https://www.readbyqxmd.com/read/28631712/-the-molecular-mechanisms-and-morphological-manifestations-of-leiomyoma-reduction-induced-by-selective-progesterone-receptor-modulators
#9
T A Demura, Z V Revazova, E A Kogan, L V Adamyan
AIM: to investigate the molecular mechanisms and morphological substrate of reduced uterine leiomyoma in patients receiving the selective progesterone receptor modulator (SPRM) ulipristal acetate for 3 months, by estimating the immunohistochemical expression of the markers steroid receptor coactivator 1 (SRC-1), nuclear receptor corepressor 1 (NCoR-1), ER, PgR, Ki-67, p16, TGF-β, and VEGF in tumor tissue. SUBJECTS AND METHODS: The investigation enrolled 75 women with uterine leiomyoma, menorrhagias, and anemia...
2017: Arkhiv Patologii
https://www.readbyqxmd.com/read/28611094/agonist-specific-protein-interactomes-of-glucocorticoid-and-androgen-receptor-as-revealed-by-proximity-mapping
#10
Joanna K Lempiäinen, Einari A Niskanen, Kaisa-Mari Vuoti, Riikka E Lampinen, Helka Göös, Markku Varjosalo, Jorma J Palvimo
Glucocorticoid receptor (GR) and androgen receptor (AR) are steroid-inducible transcription factors (TFs). The GR and the AR are central regulators of various metabolic, homeostatic and differentiation processes and hence important therapeutic targets, especially in inflammation and prostate cancer, respectively. Hormone binding to these steroid receptors (SRs) leads to DNA binding and activation or repression of their target genes with the aid of interacting proteins, coregulators. However, protein interactomes of these important drug targets have remained poorly defined...
August 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28611048/targeting-src-coactivators-blocks-the-tumor-initiating-capacity-of-cancer-stem-like-cells
#11
Aarti D Rohira, Fei Yan, Lei Wang, Jin Wang, Suoling Zhou, Andrew Lu, Yang Yu, Jianming Xu, David M Lonard, Bert W O'Malley
Tumor-initiating cells (TIC) represent cancer stem-like cell (CSC) subpopulations within tumors that are thought to give rise to recurrent cancer after therapy. Identifying key regulators of TIC/CSC maintenance is essential for the development of therapeutics designed to limit recurrence. The steroid receptor coactivator 3 (SRC-3) is overexpressed in a wide range of cancers, driving tumor initiation, cell proliferation, and metastasis. Here we report that SRC-3 supports the TIC/CSC state and induces an epithelial-to-mesenchymal transition (EMT) by driving expression of the master EMT regulators and stem cell markers...
August 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28610887/a-hormonal-cue-promotes-timely-follicle-cell-migration-by-modulating-transcription-profiles
#12
Lathiena Manning, Jinal Sheth, Stacey Bridges, Afsoon Saadin, Kamsi Odinammadu, Deborah Andrew, Susan Spencer, Denise Montell, Michelle Starz-Gaiano
Cell migration is essential during animal development. In the Drosophila ovary, the steroid hormone ecdysone coordinates nutrient sensing, growth, and the timing of morphogenesis events including border cell migration. To identify downstream effectors of ecdysone signaling, we profiled gene expression in wild-type follicle cells compared to cells expressing a dominant negative Ecdysone receptor or its coactivator Taiman. Of approximately 400 genes that showed differences in expression, we validated 16 candidate genes for expression in border and centripetal cells, and demonstrated that seven responded to ectopic ecdysone activation by changing their transcriptional levels...
June 10, 2017: Mechanisms of Development
https://www.readbyqxmd.com/read/28589840/characterization-of-a-sea-urchin-iq-motif-containing-protein-d-as-a-coactivator-of-nuclear-receptors
#13
Mi Ae Kim, Young Chang Sohn
Nuclear receptor (NR) interacting proteins, such as coactivators and corepressors, play a crucial role in specifying the transcriptional activity of the receptor. However, little is known about the functional features of the NR coregulators in marine invertebrates. Using the yeast two-hybrid screening method, a sea urchin oocyte cDNA library was screened for proteins that interact with the ligand-binding domain of human RXRα (hRXRα) as the bait protein in the presence of 9-cis retinoic acid. Here, we describe IQ motif containing protein D (IQCD) as an RXR-interacting coactivator...
June 2017: Zoological Science
https://www.readbyqxmd.com/read/28521488/mir-137-inhibits-the-proliferation-of-human-non-small-cell-lung-cancer-cells-by-targeting-src3
#14
Ruilin Chen, Yongqing Zhang, Chengcheng Zhang, Hua Wu, Shumei Yang
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. The results of the present study demonstrate that high expression of microRNA (miR)-137 and low expression of steroid receptor coactivator-3 (SRC3) had a significant negative correlation in 40 NSCLC tissue samples. In addition, cell colony formation and proliferation was significantly reduced in miR-137-transfected A549 and NCI-H838 cells compared with scramble-transfected NSCLC cell lines. miR-137 was identified to induce G1/S cell cycle arrest and dysregulate the mRNA expression of cell cycle-associated proteins (proliferating cell nuclear antigen, cyclin E, cyclin A1, cyclin A2 and p21) in NSCLC cells...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28521442/mrna-expression-of-steroidogenic-enzymes-steroid-hormone-receptors-and-their-coregulators-in-gastric-cancer
#15
Bartosz Adam Frycz, Dawid Murawa, Maciej Borejsza-Wysocki, Mateusz Wichtowski, Arkadiusz Spychała, Ryszard Marciniak, Paweł Murawa, Michał Drews, Paweł Piotr Jagodziński
Epidemiological and experimental findings suggest that the development of gastric cancer (GC) is regulated by steroid hormones. In postmenopausal women and older men, the majority of steroid hormones are produced locally in peripheral tissue through the enzymatic conversion of steroid precursors. Therefore, using reverse transcription-quantitative polymerase chain reaction analysis, the mRNA expression of genes encoding steroidogenic enzymes, including steroid sulfatase (STS), hydroxy-delta-5-steroid dehydrogenase 3 beta- and steroid delta-isomerase 1 (HSD3B1), 17β-hydroxysteroid dehydrogenase type 7 and aromatase (CYP19A1), was investigated in primary tumoral and adjacent healthy gastric mucosa from 60 patients with GC...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28468300/nobiletin-inhibits-angiogenesis-by-regulating-src-fak-stat3-mediated-signaling-through-pxn-in-er%C3%A2-%C2%BA-breast-cancer-cells
#16
Nipin Sp, Dong Young Kang, Youn Hee Joung, Jong Hwan Park, Wan Seop Kim, Hak Kyo Lee, Ki-Duk Song, Yeong-Min Park, Young Mok Yang
Tumor angiogenesis is one of the major hallmarks of tumor progression. Nobiletin is a natural flavonoid isolated from citrus peel that has anti-angiogenic activity. Steroid receptor coactivator (Src) is an intracellular tyrosine kinase so that focal adhesion kinase (FAK) binds to Src to play a role in tumor angiogenesis. Signal transducer and activator of transcription 3 (STAT3) is a marker for tumor angiogenesis which interacts with Src. Paxillin (PXN) acts as a downstream target for both FAK and STAT3. The main goal of this study was to assess inhibition of tumor angiogenesis by nobiletin in estrogen receptor positive (ER⁺) breast cancer cells via Src, FAK, and STAT3-mediated signaling through PXN...
April 30, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28396297/the-co-regulators-src-1-and-smrt-are-involved-in-interleukin-6-induced-androgen-receptor-activation
#17
Qi Wang, Hui Wang, Qiang Ju, Zhen Ding, Xing Ge, Qiao-Mei Shi, Ji-Long Zhou, Xiao-Long Zhou, Jin-Peng Zhang, Mei-Rong Zhang, Hong-Min Yu, Li-Chun Xu
BACKGROUND: The androgen receptor (AR) can be stimulated by interleukin-6 (IL-6) in the absence of androgens to induce prostate cancer progression. The purpose of this study was to investigate whether the co-activator steroid receptor coactivator-1 (SRC-1) and co-repressor silencing mediator for retinoid and thyroid hormone receptors (SMRT) are involved in IL-6-induced AR activation. METHODS: The effects of IL-6 on LNCaP cell proliferation were monitored using real-time cell analysis (RTCA) iCELLigence system...
November 1, 2016: European Cytokine Network
https://www.readbyqxmd.com/read/28390937/steroid-receptor-coactivators-present-a-unique-opportunity-for-drug-development-in-hormone-dependent-cancers
#18
REVIEW
Aarti D Rohira, David M Lonard
Steroid receptor coactivators (SRCs) are essential regulators of nuclear hormone receptor function. SRCs coactivate transcription mediated by hormone stimulation of nuclear receptors and other transcription factors and have essential functions in human physiology and health. The SRCs are over expressed in a number of cancers such as breast, prostate, endometrial and pancreatic cancers where they promote tumor growth, invasion, metastasis and chemo-resistance. With their multiple roles in cancer, the SRCs are promising targets for the development of small molecule agents that can interfere with their function...
September 15, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28378812/ecr-recruits-dmi-2-and-increases-efficiency-of-dmi-2-mediated-remodelling-to-constrain-transcription-of-hormone-regulated-genes
#19
Judith Kreher, Kristina Kovač, Karim Bouazoune, Igor Mačinković, Anna Luise Ernst, Erik Engelen, Roman Pahl, Florian Finkernagel, Magdalena Murawska, Ikram Ullah, Alexander Brehm
Gene regulation by steroid hormones plays important roles in health and disease. In Drosophila, the hormone ecdysone governs transitions between key developmental stages. Ecdysone-regulated genes are bound by a heterodimer of ecdysone receptor (EcR) and Ultraspiracle. According to the bimodal switch model, steroid hormone receptors recruit corepressors in the absence of hormone and coactivators in its presence. Here we show that the nucleosome remodeller dMi-2 is recruited to ecdysone-regulated genes to limit transcription...
April 5, 2017: Nature Communications
https://www.readbyqxmd.com/read/28322350/agonist-mediated-assembly-of-the-crustacean-methyl-farnesoate-receptor
#20
Elizabeth K Medlock Kakaley, Helen Y Wang, Gerald A LeBlanc
The methyl farnesoate receptor (MfR) orchestrates aspects of reproduction and development such as male sex determination in branchiopod crustaceans. Phenotypic endpoints regulated by the receptor have been well-documented, but molecular interactions involved in receptor activation remain elusive. We hypothesized that the MfR subunits, methoprene-tolerant transcription factor (Met) and steroid receptor coactivator (SRC), would be expressed coincident with the timing of sex programming of developing oocytes by methyl farnesoate in daphnids...
March 21, 2017: Scientific Reports
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