DOCSLIB.ORG

Transducin Β-Like 1, X-Linked and Nuclear Receptor Co-Repressor

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Transducin Β-Like 1, X-Linked and Nuclear Receptor Co-Repressor doi:10.1507/endocrj.EJ17-0384 ORIGINAL Transducin β-like 1, X-linked and nuclear receptor co-repressor cooperatively augment the ligand- independent stimulation of TRH and TSHβ gene promoters by thyroid hormone receptors Tetsuya Takamizawa *, Tetsurou Satoh *, Tomoko Miyamoto, Yasuyo Nakajima, Takahiro Ishizuka, Takuya Tomaru, Satoshi Yoshino, Akiko Katano-Toki, Ayaka Nishikido, Santosh Sapkota, Takuya Watanabe, Takashi Okamura, Emi Ishida, Kazuhiko Horiguchi, Syunichi Matsumoto, Sumiyasu Ishii, Atsushi Ozawa, Nobuyuki Shibusawa, Shuichi Okada and Masanobu Yamada Division of Endocrinology and Metabolism, Department of Internal Medicine, Gunma University Graduate School of Medicine, Maebashi, Japan Abstract. Mutations in TBL1X, a component of the nuclear receptor co-repressor (N-CoR) and silencing mediator of retinoic acid and thyroid hormone receptor co-repressor complexes, have recently been implicated in isolated central hypothyroidism (CeH). However, the mechanisms by which TBL1X mutations affect negative feedback regulation in the hypothalamus- pituitary-thyroid axis remain unclear. N-CoR was previously reported to paradoxically enhance the ligand-independent stimulation of TRH and TSHβ gene promoters by thyroid hormone receptors (TR) in cell culture systems. We herein investigated whether TBL1X affects the unliganded TR-mediated stimulation of the promoter activities of genes negatively regulated by T3 in cooperation with N-CoR. In a hypothalamic neuronal cell line, the unliganded TR-mediated stimulation of the TRH gene promoter was significantly enhanced by co-transfected TBL1X, and the co-transfection of TBL1X with N-CoR further enhanced promoter activity. In contrast, the knockdown of endogenous Tbl1x using short interfering RNA significantly attenuated the N-CoR-mediated enhancement of promoter activity in the presence of unliganded TR. The co-transfection of N365Y or Y458C, TBL1X mutants identified in CeH patients, showed impaired co-activation with N-CoR for the ligand- independent stimulation of the TRH promoter by TR. In the absence of T3, similar or impaired enhancement of the TSHβ gene promoter by the wild type or TBL1X mutants, respectively, was observed in the presence of co-transfected TR and N- CoR in CV-1 cells. These results suggest that TBL1X is needed for the full activation of TRH and TSHβ gene promoters by unliganded TR. Mutations in TBL1X may cause CeH due to the impaired up-regulation of TRH and/or TSHβ gene transcription despite low T3 levels. Key words: Central hypothyroidism, Transducin β-like 1, X-linked, Co-repressor, TRH, TSHβ CENTRAL HYPOTHYROIDISM (CeH) is diagnosed conditions including pituitary and hypothalamic tumors, based on plasma free T4 levels less than the reference brain surgery and irradiation, granulomatous diseases, range in combination with inappropriately normal TSH vascular diseases, infection, and trauma as well as sev- levels [1]. Acquired CeH may be caused by a number of eral drugs such as glucocorticoids, dopamine, somato- statin analogs, and a retinoid X receptor agonist [1]. On Submitted Aug. 31, 2017; Accepted Apr. 20, 2018 as EJ17-0384 the other hand, isolated congenital CeH is known to be Released online in J-STAGE as advance publication May 23, 2018 caused by mutations in TSHβ, TRHR, and IGSF1 [1-3]. Correspondence to: Tetsurou Satoh, MD, PhD, Division of Endo- In a mouse model, we previously showed that the knock- crinology and Metabolism, Department of Internal Medicine, out of Trh resulted in isolated congenital CeH [4, 5]. Gunma University Graduate School of Medicine, 3-39-15 Showa- machi, Maebashi 371-8511, Japan. Missense mutations in transducin β-like 1, X-linked E-mail: [email protected] (TBL1X), which is located on human chromosome *These authors contributed equally to this manuscript. Xp22.3-22.2, were recently shown to cause isolated CeH ©The Japan Endocrine Society 2 Takamizawa et al. frequently complicated by hearing disturbances in Dutch mechanisms by which wild-type TBL1X and mutated patients [6]. TBL1X identified in CeH patients affect the ligand- TBL1X was identified as one of the core components independent stimulation of TRH and TSHβ gene promot- in nuclear receptor co-repressor (N-CoR)/silencing medi- ers by TR in cooperation with N-CoR. ator of retinoic acid and thyroid hormone receptors (SMRT) co-repressor complexes [7, 8]. In the absence of Materials and Methods T3, the co-repressor complexes associate with DNA- bound thyroid hormone receptors (TR) in order to Cell culture actively repress the transcription of positively regulated N-1, a mouse embryonic hypothalamic cell line genes by thyroid hormone (TH) through tightly packag- immortalized by the retroviral transfer of the SV40 large ing the surrounding chromatin structure via the deacety- T-antigen, was obtained from CELLutions BIOSYSTEMS lation of histone tails [9]. The human TBL1X protein, (Westbury, NY). CV-1 cells were kindly provided by Dr. consisting of 526 amino acids, belongs to the F-box/ Shigekazu Sasaki (Hamamatsu Medical University, WD40 domain protein family [6] and is expressed in Hamamatsu, Japan). These cells were cultured in DMEM several hypothalamic nuclei including the paraventricu- supplemented with 10% FBS (Biowest, Nuaillé, France) lar nucleus and pituitary gland [6]. TBL1X was previ- and ampicillin/streptomycin (GIBCO by Life Technology). ously reported to function as a specific adaptor that recruits the ubiquitin-conjugating/19S proteasome com- Plasmids plex, which mediates the exchange of co-repressors for Firefly luciferase reporter vectors driven by the mouse co-activators in vitro [10] and also interacts with the TRH gene promoter (–256/+83 pA3Luc), human TSHβ hypoacetylated histones H2 and H4 [8]. Two mutant gene promoter (–1,192/+38 pA3Luc), and Herpes TBL1X proteins, N365Y and H453Y identified in CeH Simplex virus thymidine kinase gene promoter patients were found to be poorly expressed when tran- (TK109-pA3Luc) were described previously [11, 13, 14]. siently transfected into culture cells, and this was sugges- Expression vectors for mouse TRα1 (pRSV-TRα1), ted to be due to aberrant protein folding or stability. human TRβ1 (pKCR2-TRβ1), mouse TRβ2 (pRSV- In addition, the Y458C mutant TBL1X protein was TRβ2), and mouse N-CoR (pCMX-FLAG-mN-CoR) expressed at a similar level to the wild-type protein in were described previously [11, 13, 15]. Expression vec- transient transfection, but showed reduced thermal stabil- tors for human TBL1X (pCMV6-Entry-TBL1X) were ity in vitro [6]. This biochemical characterization of obtained from OriGene Technologies (Rockville, MD). mutated TBL1X proteins identified in CeH patients sug- Plasmids expressing GATA2 (pcDNA2.1TOPO-GATA2) gests that the instability of mutant proteins is responsible and Pit-1 (pBKCMV-Pit-1) were described previously for impaired increases in serum TSH levels in these [14]. patients; however, the molecular mechanisms by which mutant TBL1X proteins functionally disturb the nega- Total RNA isolation and RT-PCR analysis tive feedback regulation of hypothalamic TRH and/or Total RNA was isolated from N-1 and CV-1 cells pituitary TSHβ gene transcription by TH have not yet using Isogen (NIPPON GENE, Tokyo, Japan) according been elucidated. to the manufacturer ’ s protocol. Five micrograms of Previous studies and our group demonstrated that the total RNA was subjected to first-strand cDNA synthesis promoter activities of the TRH and TSHβ genes were using Superscript III reverse transcriptase (Invitrogen). stimulated or repressed by co-transfected TR in the One microliter of cDNA was amplified by PCR using absence or presence of T3, respectively, using transient AmpliTaq DNA polymerase (Thermo Fisher transfection assays [11-13] and also that the co- SCIENTIFIC). The nucleotide sequences of the PCR transfection of N-CoR/SMRT paradoxically augmented primers used were as follows: Ncor sense GTCA the ligand-independent stimulation of TRH and TSHβ CAGCCCATTTGATCCT, Ncor antisense CCTGCATC gene promoters by TR [12, 13]. However, it currently TGCTGTGAGGTA; Tbl1x sense ATCAAGTGGAGT remains unclear whether core components other than N- CCCACAGG, Tbl1x antisense TCCACTGGCCAAA CoR/SMRT in co-repressor complexes affect the unli- TACTTCC; Glyceraldehyde-3-phosphate dehydrogenase ganded TR-mediated activation of TRH and TSHβ gene (GAPDH) sense ACCACAGTCCATGCCATCAC, anti- promoters. In the present study, we investigated the sense TCCACCACCCTGTTGCTGTA. All PCR primers Endocrine Journal Advance Publication Endocrine Journal Advance Publication Regulation of TRH and TSHβ promoters by TBL1X 3 were designed from different exons of each gene in order using pCMV6-entry-TBL1X as the template. The proper to avoid genomic DNA amplification. Predicted PCR introduction of mutations was verified by nucleotide product sizes were 243 base pairs (bp) for Ncor, 192 bp sequencing. for Tbl1x, and 462 bp for Gapdh. PCR was performed under the following conditions for 35 cycles: denaturing Preparation of whole cell lysates (WCL) and at 94°C for 30 sec, annealing at 56°C for 30 sec, and immunoblotting extension at 72°C for 1 min. PCR products were separa- N-1 cells were split onto 100-mm dishes and trans- ted by agarose gel electrophoresis and stained with ethi- fected with the wild-type or mutant TBL1X expression dium bromide. Proper amplification was verified by the vector using Lipofectamine 2000 reagent (Thermo Fisher direct sequencing of PCR products. SCIENTIFIC). Media were changed after 16 hours of transfection and WCL were prepared
Load more

Recommended publications
  • A Strategic Research Alliance: Turner Syndrome and Sex Differences
    A strategic research alliance: Turner syndrome and sex differences The MIT Faculty has made this article openly available. Please share how this access benefits you. Your story matters. Citation Roman, Adrianna K. San and David C. Page. “A strategic research alliance: Turner syndrome and sex differences.” American journal of medical genetics. Part C, Seminars in medical genetics 181 (2019): 59-67 © 2019 The Author(s) As Published 10.1002/AJMG.C.31677 Publisher Wiley Version Author's final manuscript Citable link https://hdl.handle.net/1721.1/125103 Terms of Use Creative Commons Attribution-Noncommercial-Share Alike Detailed Terms http://creativecommons.org/licenses/by-nc-sa/4.0/ HHS Public Access Author manuscript Author ManuscriptAuthor Manuscript Author Am J Med Manuscript Author Genet C Semin Manuscript Author Med Genet. Author manuscript; available in PMC 2019 March 12. Published in final edited form as: Am J Med Genet C Semin Med Genet. 2019 March ; 181(1): 59–67. doi:10.1002/ajmg.c.31677. A strategic research alliance: Turner syndrome and sex differences Adrianna K. San Roman1 and David C. Page1,2,3 1Whitehead Institute, Cambridge, MA 02142, USA 2Howard Hughes Medical Institute, Whitehead Institute, Cambridge, MA 02142 3Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139 Abstract Sex chromosome constitution varies in the human population, both between the sexes (46,XX females and 46,XY males), and within the sexes (for example, 45,X and 46,XX females, and 47,XXY and 46,XY males). Coincident with this genetic variation are numerous phenotypic differences between males and females, and individuals with sex chromosome aneuploidy.
    [Show full text]
  • Central Hypothyroidism and Novel Clinical Phenotypes in Hemizygous Truncation of TBL1X
    ISSN 2472-1972 Central Hypothyroidism and Novel Clinical Phenotypes in Hemizygous Truncation of TBL1X Marta García,1 Ana C. Barreda-Bonis,2 Paula Jiménez,1 Ignacio Rabanal,3 Arancha Ortiz,4 Elena Vallespín,5 Angela´ del Pozo,6 Juan Martínez-San Millan, ´ 7 Isabel Gonzalez-Casado, ´ 2 and José C. Moreno1 1Thyroid Molecular Laboratory, Institute for Medical and Molecular Genetics (INGEMM), La Paz University Hospital, Autonomous University of Madrid, 28046 Madrid, Spain; 2Pediatric Endocrinology, La Paz University Hospital, 28046 Madrid, Spain; 3Pediatric Otorhinolaryngology, La Paz University Hospital, 28046 Madrid, Spain; 4Child and Adolescent Psychiatry, La Paz University Hospital, 28046 Madrid, Spain; 5Functional and Structural Genomics, Institute for Medical and Molecular Genetics (INGEMM), La Paz University Hospital, 28046 Madrid, Spain; 6Bioinformatics Unit, Institute for Medical and Molecular Genetics (INGEMM), La Paz University Hospital, 28046 Madrid, Spain; and 7Department of Radiology, Ram´on y Cajal Hospital, 28039 Madrid, Spain ORCiD numbers: 0000-0003-0427-2751 (M. Garcı´a); 0000-0001-5664-5308 (J. C. Moreno). Transducin b-like 1 X-linked (TBL1X) gene encodes a subunit of the nuclear corepressor-silencing mediator for retinoid and thyroid hormone receptor complex (NCoR-SMRT) involved in repression of thyroid hormone action in the pituitary and hypothalamus. TBL1X defects were recently associated with central hypo- thyroidism and hearing loss. The current study aims to describe the clinical and genetic characterization of a male diagnosed with central hypothyroidism through thyroid hormone profiling, TRH test, brain MRI, audiometry, and psychological evaluation. Next-generation sequencing of known genes involved in thyroid disorders was implemented. The 6-year-old boy was diagnosed with central hypothyroidism [free T4: 10.42 pmol/L (normal: 12 to 22 pmol/L); TSH: 1.57 mIU/L (normal: 0.7 to 5.7 mIU/L)], with a mildly reduced TSH response to TRH.
    [Show full text]
  • The Inactive X Chromosome Is Epigenetically Unstable and Transcriptionally Labile in Breast Cancer
    Downloaded from genome.cshlp.org on October 3, 2021 - Published by Cold Spring Harbor Laboratory Press Research The inactive X chromosome is epigenetically unstable and transcriptionally labile in breast cancer Ronan Chaligné,1,2,3,4 Tatiana Popova,1,5 Marco-Antonio Mendoza-Parra,6 Mohamed-Ashick M. Saleem,6 David Gentien,1,7 Kristen Ban,1,2,3,4 Tristan Piolot,1,8 Olivier Leroy,1,8 Odette Mariani,7 Hinrich Gronemeyer,6 Anne Vincent-Salomon,1,4,5,7 Marc-Henri Stern,1,5,7 and Edith Heard1,2,3,4 1Centre de Recherche, Institut Curie, 75248 Paris Cedex 05, France; 2Centre National de la Recherche Scientifique, Unité Mixte de Recherche 3215, Institut Curie, 75248 Paris Cedex 05, France; 3Institut National de la Santé et de la Recherche Médicale U934, Institut Curie, 75248 Paris Cedex 05, France; 4Equipe Labellisée Ligue Contre le Cancer, UMR3215, 75248 Paris Cedex 05, France; 5Institut National de la Santé et de la Recherche Médicale U830, Institut Curie, 75248 Paris Cedex 05, France; 6Institut de Génétique et de Biologie Moléculaire et Cellulaire, Equipe Labellisée Ligue Contre le Cancer, Centre National de la Recherche Scientifique UMR 7104, Institut National de la Santé et de la Recherche Médicale U964, University of Strasbourg, 67404 Illkirch Cedex, France; 7Department of Tumor Biology, Institut Curie, 75248 Paris Cedex 05, France; 8Plate-forme d’Imagerie Cellulaire et Tissulaire at BDD (Pict@BDD), Institut Curie, 75248 Paris Cedex 05, France Disappearance of the Barr body is considered a hallmark of cancer, although whether this corresponds to genetic loss or to epigenetic instability and transcriptional reactivation is unclear.
    [Show full text]
  • Integrative Analysis of Disease Signatures Shows Inflammation Disrupts Juvenile Experience-Dependent Cortical Plasticity
    New Research Development Integrative Analysis of Disease Signatures Shows Inflammation Disrupts Juvenile Experience- Dependent Cortical Plasticity Milo R. Smith1,2,3,4,5,6,7,8, Poromendro Burman1,3,4,5,8, Masato Sadahiro1,3,4,5,6,8, Brian A. Kidd,2,7 Joel T. Dudley,2,7 and Hirofumi Morishita1,3,4,5,8 DOI:http://dx.doi.org/10.1523/ENEURO.0240-16.2016 1Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York 10029, 2Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029, 3Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York 10029, 4Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York, New York 10029, 5Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, 6Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029, 7Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York 10029, and 8Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029 Visual Abstract Throughout childhood and adolescence, periods of heightened neuroplasticity are critical for the development of healthy brain function and behavior. Given the high prevalence of neurodevelopmental disorders, such as autism, identifying disruptors of developmental plasticity represents an essential step for developing strategies for prevention and intervention. Applying a novel computational approach that systematically assessed connections between 436 transcriptional signatures of disease and multiple signatures of neuroplasticity, we identified inflammation as a common pathological process central to a diverse set of diseases predicted to dysregulate Significance Statement During childhood and adolescence, heightened neuroplasticity allows the brain to reorganize and adapt to its environment.
    [Show full text]
  • TBL1 Antibody Purified Mouse Monoclonal Antibody (Mab) Catalog # AP53272
    10320 Camino Santa Fe, Suite G San Diego, CA 92121 Tel: 858.875.1900 Fax: 858.622.0609 TBL1 Antibody Purified Mouse Monoclonal Antibody (Mab) Catalog # AP53272 Specification TBL1 Antibody - Product Information Application WB, ICC Primary Accession O60907 Reactivity Human Host Mouse Clonality Monoclonal Isotype IgG2b Calculated MW 58 KDa TBL1 Antibody - Additional Information Gene ID 6907 Other Names EBI;F box like/WD repeat protein TBL1X;F-box-like/WD repeat-containing protein TBL1X; SMAP 55;SMAP55;TBL 1;TBL Western blot detection of TBL1X in SW480 1X;TBL1;TBL1X; TBL1X_HUMAN;Transducin cell lysates using TBL1X mouse mAb (1:1000 (beta) like 1;Transducin (beta) like 1 X diluted).Predicted band size:58KDa.Observed linked;Transducin (beta) like 1X band size:58KDa. linked;Transducin beta like 1 X linked; Transducin beta like 1X;Transducin beta like 1X protein;Transducin beta like protein 1, X linked;Transducin beta-like protein 1X;Transducin-beta-like protein 1;X-linked. Dilution WB~~1:1000 ICC~~1:100 Format Purified mouse monoclonal antibody in PBS(pH 7.4) containing with 0.02% sodium azide and 50% glycerol. Storage Store at -20 °C.Stable for 12 months from Immunocytochemistry staining of HeLa cells date of receipt fixed with 4% Paraformaldehyde and using anti-TBL1X mouse mAb (dilution 1:100). TBL1 Antibody - Protein Information TBL1 Antibody - Background Name TBL1X F-box-like protein involved in the recruitment of the ubiquitin/19S proteasome complex to Synonyms TBL1 nuclear receptor-regulated transcription units. Page 1/2 10320 Camino Santa Fe, Suite G San Diego, CA 92121 Tel: 858.875.1900 Fax: 858.622.0609 Function Plays an essential role in transcription F-box-like protein involved in the activation mediated by nuclear receptors.
    [Show full text]
  • TBL1 (TBL1X) (NM 005647) Human Recombinant Protein Product Data
    OriGene Technologies, Inc. 9620 Medical Center Drive, Ste 200 Rockville, MD 20850, US Phone: +1-888-267-4436 [email protected] EU: [email protected] CN: [email protected] Product datasheet for TP750166 TBL1 (TBL1X) (NM_005647) Human Recombinant Protein Product data: Product Type: Recombinant Proteins Description: Purified recombinant protein of Human transducin (beta)-like 1X-linked (TBL1X), transcript variant 1, full length, Tag free, expressed in E.coli, 50ug Species: Human Expression Host: E. coli Tag: Tag-free Predicted MW: 62.3 kDa Concentration: >50 ug/mL as determined by microplate BCA method Purity: > 80% as determined by SDS-PAGE and Coomassie blue staining Buffer: 50mM Tris, 500mM NaCl, 10% Glycerine,pH8.0. Storage: Store at +4°C. Stability: Stable for 12 months from the date of receipt of the product under proper storage and handling conditions. Avoid repeated freeze-thaw cycles. RefSeq: NP_005638 Locus ID: 6907 UniProt ID: O60907, A0A024RBV9 RefSeq Size: 5886 Cytogenetics: Xp22.31-p22.2 RefSeq ORF: 1731 Synonyms: CHNG8; EBI; SMAP55; TBL1 This product is to be used for laboratory only. Not for diagnostic or therapeutic use. View online » ©2021 OriGene Technologies, Inc., 9620 Medical Center Drive, Ste 200, Rockville, MD 20850, US 1 / 2 TBL1 (TBL1X) (NM_005647) Human Recombinant Protein – TP750166 Summary: The protein encoded by this gene has sequence similarity with members of the WD40 repeat- containing protein family. The WD40 group is a large family of proteins, which appear to have a regulatory function. It is believed that the WD40 repeats mediate protein-protein interactions and members of the family are involved in signal transduction, RNA processing, gene regulation, vesicular trafficking, cytoskeletal assembly and may play a role in the control of cytotypic differentiation.
    [Show full text]
  • A Scalable Random Walk with Restart on Heterogeneous Networks with Apache Spark for Ranking Disease-Causing Genes Using Type-2 Fuzzy Data Fusion
    bioRxiv preprint doi: https://doi.org/10.1101/844159; this version posted November 16, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. A scalable random walk with restart on heterogeneous networks with Apache Spark for ranking disease-causing genes using type-2 fuzzy data fusion Mehdi Joodaki, Nasser Ghadiri, Zeinab Maleki, Maryam Lotfi Shahreza Department of Electrical and Computer Engineering, Isfahan University of Technology, Isfahan 84156-83111, Iran [email protected], [email protected], [email protected], [email protected] Abstract Prediction and discovery of disease-causing genes are among the main missions of biology and medicine. In recent years, researchers have developed several methods based on gene/protein networks for the detection of causative genes. However, because of the presence of false positives in these networks, the results of these methods often lack accuracy and reliability. This problem can be solved by using multiple genomic sources to reduce noise in data. However, network integration can also affect the quality of the integrated network. In this paper, we present a method named RWRHN (random walk with restart on a heterogeneous network) with fuzzy fusion or RWRHN-FF. In this method, first, four gene-gene similarity networks are constructed based on different genomic sources and then integrated using the type-II fuzzy voter scheme. The resulting gene-gene network is then linked to a disease-disease similarity network, which itself is constructed by the integration of four sources, through a two-part disease-gene network.
    [Show full text]
  • Table S1. 103 Ferroptosis-Related Genes Retrieved from the Genecards
    Table S1. 103 ferroptosis-related genes retrieved from the GeneCards. Gene Symbol Description Category GPX4 Glutathione Peroxidase 4 Protein Coding AIFM2 Apoptosis Inducing Factor Mitochondria Associated 2 Protein Coding TP53 Tumor Protein P53 Protein Coding ACSL4 Acyl-CoA Synthetase Long Chain Family Member 4 Protein Coding SLC7A11 Solute Carrier Family 7 Member 11 Protein Coding VDAC2 Voltage Dependent Anion Channel 2 Protein Coding VDAC3 Voltage Dependent Anion Channel 3 Protein Coding ATG5 Autophagy Related 5 Protein Coding ATG7 Autophagy Related 7 Protein Coding NCOA4 Nuclear Receptor Coactivator 4 Protein Coding HMOX1 Heme Oxygenase 1 Protein Coding SLC3A2 Solute Carrier Family 3 Member 2 Protein Coding ALOX15 Arachidonate 15-Lipoxygenase Protein Coding BECN1 Beclin 1 Protein Coding PRKAA1 Protein Kinase AMP-Activated Catalytic Subunit Alpha 1 Protein Coding SAT1 Spermidine/Spermine N1-Acetyltransferase 1 Protein Coding NF2 Neurofibromin 2 Protein Coding YAP1 Yes1 Associated Transcriptional Regulator Protein Coding FTH1 Ferritin Heavy Chain 1 Protein Coding TF Transferrin Protein Coding TFRC Transferrin Receptor Protein Coding FTL Ferritin Light Chain Protein Coding CYBB Cytochrome B-245 Beta Chain Protein Coding GSS Glutathione Synthetase Protein Coding CP Ceruloplasmin Protein Coding PRNP Prion Protein Protein Coding SLC11A2 Solute Carrier Family 11 Member 2 Protein Coding SLC40A1 Solute Carrier Family 40 Member 1 Protein Coding STEAP3 STEAP3 Metalloreductase Protein Coding ACSL1 Acyl-CoA Synthetase Long Chain Family Member 1 Protein
    [Show full text]
  • TBL1 (TBL1X) (NM 001139468) Human Tagged ORF Clone Product Data
    OriGene Technologies, Inc. 9620 Medical Center Drive, Ste 200 Rockville, MD 20850, US Phone: +1-888-267-4436 [email protected] EU: [email protected] CN: [email protected] Product datasheet for RC226934 TBL1 (TBL1X) (NM_001139468) Human Tagged ORF Clone Product data: Product Type: Expression Plasmids Product Name: TBL1 (TBL1X) (NM_001139468) Human Tagged ORF Clone Tag: Myc-DDK Symbol: TBL1X Synonyms: CHNG8; EBI; SMAP55; TBL1 Vector: pCMV6-Entry (PS100001) E. coli Selection: Kanamycin (25 ug/mL) Cell Selection: Neomycin This product is to be used for laboratory only. Not for diagnostic or therapeutic use. View online » ©2021 OriGene Technologies, Inc., 9620 Medical Center Drive, Ste 200, Rockville, MD 20850, US 1 / 4 TBL1 (TBL1X) (NM_001139468) Human Tagged ORF Clone – RC226934 ORF Nucleotide >RC226934 representing NM_001139468 Sequence: Red=Cloning site Blue=ORF Green=Tags(s) TTTTGTAATACGACTCACTATAGGGCGGCCGGGAATTCGTCGACTGGATCCGGTACCGAGGAGATCTGCC GCCGCGATCGCC ATGAGCATAACCAGTGACGAGGTGAACTTTCTGGTGTATCGGTATCTCCAGGAGTCAGGTTTTTCCCACT CGGCTTTCACGTTTGGGATTGAGAGCCACATCAGCCAGTCCAACATCAATGGGACGCTAGTGCCACCGGC CGCCCTCATCTCCATTCTCCAGAAGGGCCTGCAGTATGTAGAGGCCGAGATCAGTATCAACGAGGATGGC ACAGTGTTCGACGGCCGCCCCATAGAGTCCCTGTCACTGATAGACGCCGTGATGCCCGACGTGGTGCAGA CGCGGCAGCAGGCATTCCGAGAGAAGCTCGCTCAGCAGCAAGCCAGTGCGGCGGCGGCGGCGGCTGCGGC CACGGCAGCAGCGACAGCAGCCACCACGACCTCAGCCGGCGTTTCCCACCAAAATCCATCGAAGAACAGA GAGGCCACGGTGAATGGGGAAGAGAACAGAGCACATTCAGTCAATAATCACGCGAAGCCAATGGAAATAG ATGGAGAGGTTGAGATTCCATCCAGCAAAGCCACAGTCCTTCGGGGCCATGAGTCTGAGGTGTTCATTTG TGCCTGGAATCCTGTCAGTGATTTGCTAGCCTCCGGATCCGGAGACTCAACTGCAAGGATATGGAACCTG
    [Show full text]
  • TBL1X Antibody Cat
    TBL1X Antibody Cat. No.: 15-880 TBL1X Antibody Specifications HOST SPECIES: Rabbit SPECIES REACTIVITY: Human, Mouse, Rat A synthetic peptide corresponding to a sequence within amino acids 100-200 of human IMMUNOGEN: TBL1X (NP_005638.1). TESTED APPLICATIONS: WB APPLICATIONS: WB: ,1:500 - 1:2000 POSITIVE CONTROL: 1) BxPC-3 2) HeLa 3) mouse brain 4) mouse lung PREDICTED MOLECULAR Observed: 60kDa WEIGHT: Properties PURIFICATION: Affinity purification CLONALITY: Polyclonal October 2, 2021 1 https://www.prosci-inc.com/tbl1x-antibody-15-880.html ISOTYPE: IgG CONJUGATE: Unconjugated PHYSICAL STATE: Liquid BUFFER: PBS with 0.02% sodium azide, 50% glycerol, pH7.3. STORAGE CONDITIONS: Store at -20˚C. Avoid freeze / thaw cycles. Additional Info OFFICIAL SYMBOL: TBL1X TBL1X, EBI, TBL1, transducin (beta)-like 1X-linked, transducin (beta)-like 1, transducin ALTERNATE NAMES: (beta)-like 1 X-linked, TBL1XR1, transducin (beta)-like 1X-linked receptor 1, C21, DC42, FLJ12894, IRA1, TBLR1, TBL1-related protein 1, nuclear receptor co-repressor GENE ID: 6907 USER NOTE: Optimal dilutions for each application to be determined by the researcher. Background and References The protein encoded by this gene has sequence similarity with members of the WD40 repeat-containing protein family. The WD40 group is a large family of proteins, which appear to have a regulatory function. It is believed that the WD40 repeats mediate protein-protein interactions and members of the family are involved in signal transduction, RNA processing, gene regulation, vesicular trafficking, cytoskeletal assembly and may play a role in the control of cytotypic differentiation. This encoded protein is BACKGROUND: found as a subunit in corepressor SMRT (silencing mediator for retinoid and thyroid receptors) complex along with histone deacetylase 3 protein.
    [Show full text]
  • Role of GPS2 in the Regulation of Adipocyte Fate and Function: a Multi-Omics Approach
    From the Department of Biosciences and Nutrition Karolinska Institutet, Stockholm, Sweden Role of GPS2 in the regulation of adipocyte fate and function: a multi-omics approach Serena Barilla Stockholm 2020 Cover illustration: microscopy pictures of mature adipocytes (pink) in a GPS2 mask All previously published papers were reproduced with permission from the publisher. Published by Karolinska Institutet. Printed by US-AB © Serena Barilla, 2020 ISBN 978-91-7831-960-2 Role of GPS2 in the regulation of adipocyte fate and function: a multi-omics approach Thesis for Doctoral Degree (Ph.D.) By Serena Barilla Principal Supervisor: Opponent: Professor Eckardt Treuter Professor Christian Wolfrum Karolinska Institutet ETH Zurich Department of Biosciences and Nutrition Department of Health Sciences and Technology Co-supervisor(s): Examination Board: Dr. Marco Giudici Professor Ewa Ehrenborg KTH Karolinska Institutet School of Engineering Sciences in Department of Medicine Chemistry, Biotechnology and Health Associate Professor Andreas Lennartsson Dr. Hui Gao Karolinska Institutet Karolinska Institutet Department of Biosciences and Nutrition Department of Biosciences and Nutrition Dr. Natasa Petrovic Stockholm University Department of Molecular Biosciences To my beloved parents Rosella & Giuseppe ABSTRACT The escalating prevalence of obesity and its association with comorbidities like insulin resistance and type 2 diabetes have raised the interest in adipose tissue biology and its therapeutic potential. Adipose tissue remodeling during the development of obesity is an important regulator of systemic metabolic homeostasis, and dysfunctional adipose tissue is linked to the risk of developing type 2 diabetes. Adipocyte differentiation and function are orchestrated by a complex network of transcription factors and coregulators that transduce regulatory signals into epigenome alterations and transcriptional responses.
    [Show full text]
  • Review Article TBL1XR1 in Physiological and Pathological States
    Am J Clin Exp Urol 2015;3(1):13-23 www.ajceu.us /ISSN:2330-1910/AJCEU0008636 Review Article TBL1XR1 in physiological and pathological states Jian Yi Li1, Garrett Daniels2, Jing Wang1, Xinmin Zhang1 1Department of Pathology and Laboratory Medicine, Hofstra North Shore-LIJ School of Medicine, New York, USA; 2Department of Pathology, New York University School of Medicine, New York, USA Received March 31, 2015; Accepted April 1, 2015; Epub April 25, 2015; Published April 30, 2015 Abstract: Transducin (beta)-like 1X related protein 1 (TBL1XR1/TBLR1) is an integral subunit of the NCoR (nuclear receptor corepressor) and SMRT (silencing mediator of retinoic acid and thyroid hormone receptors) repressor com- plexes. It is an evolutionally conserved protein that shares high similarity across all species. TBL1XR1 is essential for transcriptional repression mediated by unliganded nuclear receptors (NRs) and othe regulated transcription factors (TFs). However, it can also act as a transcription activator through the recruitment of the ubiquitin-conjugating/19S proteasome complex that mediates the exchange of corepressors for coactivators. TBL1XR1 is required for the activation of multiple intracellular signaling pathways. TBL1XR1 germline mutations and recurrent mutations are linked to intellectual disability. Upregulation of TBL1XR1 is observed in a variety of solid tumors, which is associated with advanced tumor stage, metastasis and poor prognosis. A variety of genomic alterations, such as translocation, deletion and mutation have been identified in many types of neoplasms. Loss of TBL1XR1 in B-lymphoblastic leuke- mia disrupts glucocorticoid receptor recruitment to chromatin and results in glucocorticoid resistance. However, the mechanisms of other types of genomic changes in tumorogenesis are still not clear.
    [Show full text]