Distinct Ranbp1 Nuclear Export and Cargo Dissociation Mechanisms
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XPO1E571K Mutation Modifies Exportin 1 Localisation And
cancers Article XPO1E571K Mutation Modifies Exportin 1 Localisation and Interactome in B-Cell Lymphoma Hadjer Miloudi 1, Élodie Bohers 1,2, François Guillonneau 3 , Antoine Taly 4,5 , Vincent Cabaud Gibouin 6,7 , Pierre-Julien Viailly 1,2 , Gaëtan Jego 6,7 , Luca Grumolato 8 , Fabrice Jardin 1,2 and Brigitte Sola 1,* 1 INSERM U1245, Unicaen, Normandie University, F-14000 Caen, France; [email protected] (H.M.); [email protected] (E.B.); [email protected] (P.-J.V.); [email protected] (F.J.) 2 Centre de lutte contre le Cancer Henri Becquerel, F-76000 Rouen, France 3 Plateforme Protéomique 3P5, Université de Paris, Institut Cochin, INSERM, CNRS, F-75014 Paris, France; [email protected] 4 Laboratoire de Biochimie Théorique, CNRS UPR 9030, Université de Paris, F-75005 Paris, France; [email protected] 5 Institut de Biologie Physico-Chimique, Fondation Edmond de Rothschild, PSL Research University, F-75005 Paris, France 6 INSERM, LNC UMR1231, F-21000 Dijon, France; [email protected] (V.C.G.); [email protected] (G.J.) 7 Team HSP-Pathies, University of Burgundy and Franche-Comtée, F-21000 Dijon, France 8 INSERM U1239, Unirouen, Normandie University, F-76130 Mont-Saint-Aignan, France; [email protected] * Correspondence: [email protected]; Tel.: +33-2-3156-8210 Received: 11 September 2020; Accepted: 28 September 2020; Published: 30 September 2020 Simple Summary: Almost 25% of patients with either primary mediastinal B-cell lymphoma (PMBL) or classical Hodgkin lymphoma (cHL) possess a recurrent mutation of the XPO1 gene encoding the major nuclear export protein. -
Targeting the Nuclear Import Receptor Kpnb1 As an Anticancer Therapeutic
Published OnlineFirst February 1, 2016; DOI: 10.1158/1535-7163.MCT-15-0052 Small Molecule Therapeutics Molecular Cancer Therapeutics Targeting the Nuclear Import Receptor Kpnb1as an Anticancer Therapeutic Pauline J. van der Watt1, Alicia Chi1, Tamara Stelma1, Catherine Stowell1, Erin Strydom1, Sarah Carden1, Liselotte Angus1, Kate Hadley1, Dirk Lang2, Wei Wei3, Michael J. Birrer3, John O. Trent4, and Virna D. Leaner1 Abstract Karyopherin beta 1 (Kpnb1) is a nuclear transport receptor tissue origins. Minimum effect on the proliferation of non- that imports cargoes into the nucleus. Recently, elevated Kpnb1 cancer cells was observed at the concentration of INI-43 that expression was found in certain cancers and Kpnb1silencing showed a significant cytotoxic effect on various cervical and with siRNA was shown to induce cancer cell death. This study esophageal cancer cell lines. A rescue experiment confirmed aimed to identify novel small molecule inhibitors of Kpnb1, that INI-43 exerted its cell killing effects, in part, by targeting and determine their anticancer activity. An in silico screen Kpnb1. INI-43 treatment elicited a G2–M cell-cycle arrest in identified molecules that potentially bind Kpnb1 and Inhibitor cancer cells and induced the intrinsic apoptotic pathway. Intra- of Nuclear Import-43, INI-43 (3-(1H-benzimidazol-2-yl)-1-(3- peritoneal administration of INI-43 significantly inhibited the dimethylaminopropyl)pyrrolo[5,4-b]quinoxalin-2-amine) was growth of subcutaneously xenografted esophageal and cervical investigated further as it interfered with the nuclear localization tumor cells. We propose that Kpnb1 inhibitors could have of Kpnb1andknownKpnb1cargoesNFAT,NFkB, AP-1, and therapeutic potential for the treatment of cancer. -
UNIVERSITY of CALIFORNIA, SAN DIEGO Functional Analysis of Sall4
UNIVERSITY OF CALIFORNIA, SAN DIEGO Functional analysis of Sall4 in modulating embryonic stem cell fate A dissertation submitted in partial satisfaction of the requirements for the degree Doctor of Philosophy in Molecular Pathology by Pei Jen A. Lee Committee in charge: Professor Steven Briggs, Chair Professor Geoff Rosenfeld, Co-Chair Professor Alexander Hoffmann Professor Randall Johnson Professor Mark Mercola 2009 Copyright Pei Jen A. Lee, 2009 All rights reserved. The dissertation of Pei Jen A. Lee is approved, and it is acceptable in quality and form for publication on microfilm and electronically: ______________________________________________________________ ______________________________________________________________ ______________________________________________________________ ______________________________________________________________ Co-Chair ______________________________________________________________ Chair University of California, San Diego 2009 iii Dedicated to my parents, my brother ,and my husband for their love and support iv Table of Contents Signature Page……………………………………………………………………….…iii Dedication…...…………………………………………………………………………..iv Table of Contents……………………………………………………………………….v List of Figures…………………………………………………………………………...vi List of Tables………………………………………………….………………………...ix Curriculum vitae…………………………………………………………………………x Acknowledgement………………………………………………….……….……..…...xi Abstract………………………………………………………………..…………….....xiii Chapter 1 Introduction ..…………………………………………………………………………….1 Chapter 2 Materials and Methods……………………………………………………………..…12 -
Distinct Basket Nucleoporins Roles in Nuclear Pore Function and Gene Expression
bioRxiv preprint doi: https://doi.org/10.1101/685263; this version posted June 28, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. Distinct Basket Nucleoporins roles in Nuclear Pore Function and Gene Expression: Tpr is an integral component of the TREX-2 mRNA export pathway Vasilisa Aksenova1, Hang Noh Lee1, †, Alexandra Smith1, †, Shane Chen1, †, Prasanna Bhat3, †, James Iben2, Carlos Echeverria1, Beatriz Fontoura3, Alexei Arnaoutov1 and Mary Dasso1, * 1Division of Molecular and Cellular Biology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. 2Molecular Genomics Core, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20879 3Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. † These authors contributed equally to this work. *Correspondence: [email protected]. Acronyms: NPC – nuclear pore complex; BSK-NUPs – basket nucleoporins; NG – NeonGreen; AID - Auxin Inducible Degron 1 bioRxiv preprint doi: https://doi.org/10.1101/685263; this version posted June 28, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. Abstract Nuclear pore complexes (NPCs) are important for many processes beyond nucleocytoplasmic trafficking, including protein modification, chromatin remodeling, transcription, mRNA processing and mRNA export. -
Goat Anti-RCBTB2 Antibody Size: 100Μg Specific Antibody in 200Μl
EB09067 - Goat Anti-RCBTB2 Antibody Size: 100µg specific antibody in 200µl Target Protein Principal Names: RCBTB2, regulator of chromosome condensation (RCC1) and BTB (POZ) domain containing protein 2, CHC1L, OTTHUMP00000018399, RCC1-like G UK Office exchanging factor RLG, chromosome condensation 1-like, regulator of chromosome condensation and BTB domain containing protein 2 Everest Biotech Ltd Official Symbol: RCBTB2 Cherwell Innovation Centre Accession Number(s): NP_001259.1 77 Heyford Park Human GeneID(s): 1102 Upper Heyford Non-Human GeneID(s): 105670 (mouse), 290363 (rat) Oxfordshire Important Comments: This antibody is not expected to cross-react with RCBTB1. OX25 5HD UK Immunogen Peptide with sequence CEHFRSSLEDNEDD, from the internal region of the protein Enquiries: sequence according to NP_001259.1. [email protected] Sales: Please note the peptide is available for sale. [email protected] Tech support: Purification and Storage [email protected] Purified from goat serum by ammonium sulphate precipitation followed by antigen affinity chromatography using the immunizing peptide. Tel: +44 (0)1869 238326 Supplied at 0.5 mg/ml in Tris saline, 0.02% sodium azide, pH7.3 with 0.5% bovine serum Fax: +44 (0)1869 238327 albumin. Aliquot and store at -20°C. Minimize freezing and thawing. US Office Everest Biotech c/o Abcore Applications Tested 405 Maple Street, Suite A106 Peptide ELISA: antibody detection limit dilution 1:2000. Ramona, Western blot: Preliminary experiments gave an approx. 30kDa band in Human Liver, CA 92065 Lung and Tonsil lysates after 1µg/ml antibody staining. Please note that currently we USA cannot find an explanation in the literature for the band we observe given the calculated size of 60.3kDa according to NP_001259.1. -
1 Supporting Information for a Microrna Network Regulates
Supporting Information for A microRNA Network Regulates Expression and Biosynthesis of CFTR and CFTR-ΔF508 Shyam Ramachandrana,b, Philip H. Karpc, Peng Jiangc, Lynda S. Ostedgaardc, Amy E. Walza, John T. Fishere, Shaf Keshavjeeh, Kim A. Lennoxi, Ashley M. Jacobii, Scott D. Rosei, Mark A. Behlkei, Michael J. Welshb,c,d,g, Yi Xingb,c,f, Paul B. McCray Jr.a,b,c Author Affiliations: Department of Pediatricsa, Interdisciplinary Program in Geneticsb, Departments of Internal Medicinec, Molecular Physiology and Biophysicsd, Anatomy and Cell Biologye, Biomedical Engineeringf, Howard Hughes Medical Instituteg, Carver College of Medicine, University of Iowa, Iowa City, IA-52242 Division of Thoracic Surgeryh, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Canada-M5G 2C4 Integrated DNA Technologiesi, Coralville, IA-52241 To whom correspondence should be addressed: Email: [email protected] (M.J.W.); yi- [email protected] (Y.X.); Email: [email protected] (P.B.M.) This PDF file includes: Materials and Methods References Fig. S1. miR-138 regulates SIN3A in a dose-dependent and site-specific manner. Fig. S2. miR-138 regulates endogenous SIN3A protein expression. Fig. S3. miR-138 regulates endogenous CFTR protein expression in Calu-3 cells. Fig. S4. miR-138 regulates endogenous CFTR protein expression in primary human airway epithelia. Fig. S5. miR-138 regulates CFTR expression in HeLa cells. Fig. S6. miR-138 regulates CFTR expression in HEK293T cells. Fig. S7. HeLa cells exhibit CFTR channel activity. Fig. S8. miR-138 improves CFTR processing. Fig. S9. miR-138 improves CFTR-ΔF508 processing. Fig. S10. SIN3A inhibition yields partial rescue of Cl- transport in CF epithelia. -
Rangap1 Induces Gtpase Activity of Nuclear Ras-Related Ran (Gtpase-Activating Protein/Rccl/TC4/G2 Checkpoint) F
Proc. Nati. Acad. Sci. USA Vol. 91, pp. 2587-2591, March 1994 Biochemistry RanGAP1 induces GTPase activity of nuclear Ras-related Ran (GTPase-activating protein/RCCl/TC4/G2 checkpoint) F. RALF BISCHOFF*t, CHRISTIAN KLEBEt, JURGEN KRETSCHMER*, ALFRED WITrINGHOFERt, AND HERWIG PONSTINGL* *Division for Molecular Biology of Mitosis, German Cancer Research Center, D-69120 Heidelberg, Federal Republic of Germany; and *Abteilung Strukturelle Biologie, Max-Planck-Institut ffr Molekulare Physiologie, D-44139 Dortmund, Federal Republic of Germany Communicated by Hans Neurath, December 3, 1993 ABSTRACT The nuclear Ras-related protein Ran binds DMAE-650/M (Merck; Superformance, 26 x 115 mm) in 20 guanine nucleotide and is involved in cell cycle regulation. mM Bis-Tris-propane HCl, pH 7.0/1 mM DTT with a linear Models of the signal pathway predict Ran to be active as gradient of NaCl from 0.05 M to 1 M at a flow rate of 5 Ran GTP at the initiation of S phase upon activation by the ml/min. Fractions containing RanGAP were pooled and nucleotide exchange factor RCC1 and to be inactivated for the immediately applied to a hydroxylapatite column (Merck; onset of mitosis by hydrolysis of bound GTP. Here a nuclear Superformance, 10 x 150 mm) in 20 mM potassium phos- homodimeric 65-kDa protein, RanGAPl, is described, which phate, pH 7.0/1 mM DTT, with a linear gradient from 20 mM we believe to be the immediate antagonist of RCC1. It was to 1 M phosphate at a flow rate of 2 ml/min. To fractions purified from HeLa cell lysates and induces GTPase activity of containing RanGAP, ammonium sulfate in 20 mM Bis-Tris- Ran, but not Ras, by more than 3 orders of magnitude. -
T-Cell Receptor (TCR) Signaling Promotes the Assembly of Ranbp2
RESEARCH ARTICLE T-cell receptor (TCR) signaling promotes the assembly of RanBP2/RanGAP1- SUMO1/Ubc9 nuclear pore subcomplex via PKC--mediated phosphorylation of RanGAP1 Yujiao He1, Zhiguo Yang1†, Chen-si Zhao1†, Zhihui Xiao1†, Yu Gong1, Yun-Yi Li1, Yiqi Chen1, Yunting Du1, Dianying Feng1, Amnon Altman2, Yingqiu Li1* 1MOE Key Laboratory of Gene Function and Regulation, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China; 2Center for Cancer Immunotherapy, La Jolla Institute for Immunology, La Jolla, United States Abstract The nuclear pore complex (NPC) is the sole and selective gateway for nuclear transport, and its dysfunction has been associated with many diseases. The metazoan NPC subcomplex RanBP2, which consists of RanBP2 (Nup358), RanGAP1-SUMO1, and Ubc9, regulates the assembly and function of the NPC. The roles of immune signaling in regulation of NPC remain poorly understood. Here, we show that in human and murine T cells, following T-cell receptor (TCR) stimulation, protein kinase C-q (PKC-q) directly phosphorylates RanGAP1 to facilitate RanBP2 subcomplex assembly and nuclear import and, thus, the nuclear translocation of AP-1 transcription *For correspondence: factor. Mechanistically, TCR stimulation induces the translocation of activated PKC-q to the NPC, 504 506 [email protected] where it interacts with and phosphorylates RanGAP1 on Ser and Ser . RanGAP1 phosphorylation increases its binding affinity for Ubc9, thereby promoting sumoylation of RanGAP1 †These authors contributed and, finally, assembly of the RanBP2 subcomplex. Our findings reveal an unexpected role of PKC-q equally to this work as a direct regulator of nuclear import and uncover a phosphorylation-dependent sumoylation of Competing interests: The RanGAP1, delineating a novel link between TCR signaling and assembly of the RanBP2 NPC authors declare that no subcomplex. -
Association of Gene Ontology Categories with Decay Rate for Hepg2 Experiments These Tables Show Details for All Gene Ontology Categories
Supplementary Table 1: Association of Gene Ontology Categories with Decay Rate for HepG2 Experiments These tables show details for all Gene Ontology categories. Inferences for manual classification scheme shown at the bottom. Those categories used in Figure 1A are highlighted in bold. Standard Deviations are shown in parentheses. P-values less than 1E-20 are indicated with a "0". Rate r (hour^-1) Half-life < 2hr. Decay % GO Number Category Name Probe Sets Group Non-Group Distribution p-value In-Group Non-Group Representation p-value GO:0006350 transcription 1523 0.221 (0.009) 0.127 (0.002) FASTER 0 13.1 (0.4) 4.5 (0.1) OVER 0 GO:0006351 transcription, DNA-dependent 1498 0.220 (0.009) 0.127 (0.002) FASTER 0 13.0 (0.4) 4.5 (0.1) OVER 0 GO:0006355 regulation of transcription, DNA-dependent 1163 0.230 (0.011) 0.128 (0.002) FASTER 5.00E-21 14.2 (0.5) 4.6 (0.1) OVER 0 GO:0006366 transcription from Pol II promoter 845 0.225 (0.012) 0.130 (0.002) FASTER 1.88E-14 13.0 (0.5) 4.8 (0.1) OVER 0 GO:0006139 nucleobase, nucleoside, nucleotide and nucleic acid metabolism3004 0.173 (0.006) 0.127 (0.002) FASTER 1.28E-12 8.4 (0.2) 4.5 (0.1) OVER 0 GO:0006357 regulation of transcription from Pol II promoter 487 0.231 (0.016) 0.132 (0.002) FASTER 6.05E-10 13.5 (0.6) 4.9 (0.1) OVER 0 GO:0008283 cell proliferation 625 0.189 (0.014) 0.132 (0.002) FASTER 1.95E-05 10.1 (0.6) 5.0 (0.1) OVER 1.50E-20 GO:0006513 monoubiquitination 36 0.305 (0.049) 0.134 (0.002) FASTER 2.69E-04 25.4 (4.4) 5.1 (0.1) OVER 2.04E-06 GO:0007050 cell cycle arrest 57 0.311 (0.054) 0.133 (0.002) -
Gene Section Review
Atlas of Genetics and Cytogenetics in Oncology and Haematology OPEN ACCESS JOURNAL INIST-CNRS Gene Section Review RANBP2 (RAN binding protein 2) Erica Di Cesare, Patrizia Lavia Institute of Biology, Molecular Medicine and NanoBiotechnology (IBMN), National Research Council (CNR), c/o La Sapienza University, via degli Apuli 4, 00185 Rome, Italy (ED, PL) Published in Atlas Database: August 2014 Online updated version : http://AtlasGeneticsOncology.org/Genes/RANBP2ID483.html Printable original version : http://documents.irevues.inist.fr/bitstream/handle/2042/62145/08-2014-RANBP2ID483.pdf DOI: 10.4267/2042/62145 This article is an update of : Di Cesare E, Lavia P. RANBP2 (RAN binding protein 2). Atlas Genet Cytogenet Oncol Haematol 2015;19(6) Huret JL, Senon S. RANBP2 (RAN binding protein). Atlas Genet Cytogenet Oncol Haematol 2003;7(4) This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence. © 2015 Atlas of Genetics and Cytogenetics in Oncology and Haematology alternative splicing variants (AceView; NCBI; Abstract GeneCards). Review on RANBP2, with data on DNA/RNA, on Transcription the protein encoded and where the gene is implicated. RANBP2 mRNA transcription is widespread in many though not all tissues (Fauser et al., 2001). In the mouse genome, the Ranbp2 promoter region lies Identity in a CpG island, typical of "housekeeping" gene Other names: ADANE, ANE1, NUP358 promoters and potentially subjected to epigenetic regulation. In silico analysis of the human RANBP2 HGNC (Hugo): RANBP2 gene promoter has identified potential binding sites Location: 2q12.3 for cell cycle- and cell proliferation-dependent Note transcription factors, some validated in chromatin The human RANBP2 gene lies within a immunoprecipitation (ChIP) assays (e.g., c-Fos, AP1 recombination "hot spot" genomic region on Chr and others) (GeneCards). -
In Vivo Loss-Of-Function Screens Identify KPNB1 As a New Druggable
In vivo loss-of-function screens identify KPNB1 as a PNAS PLUS new druggable oncogene in epithelial ovarian cancer Michiko Kodamaa,b,1, Takahiro Kodamaa,c,1,2, Justin Y. Newberga,d, Hiroyuki Katayamae, Makoto Kobayashie, Samir M. Hanashe, Kosuke Yoshiharaf, Zhubo Weia, Jean C. Tiena,g, Roberto Rangela,h, Kae Hashimotob, Seiji Mabuchib, Kenjiro Sawadab, Tadashi Kimurab, Neal G. Copelanda,i, and Nancy A. Jenkinsa,i,2 aCancer Research Program, Houston Methodist Research Institute, Houston, TX 77030; bDepartment of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Osaka 5650871, Japan; cDepartment of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka 5650871, Japan; dDepartment of Molecular Oncology, Moffitt Cancer Center, Tampa, FL 33612; eDepartment of Clinical Cancer Prevention, University of Texas MD Anderson Cancer Center, Houston, TX 77030; fDepartment of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 9518510, Japan; gDepartment of Pathology, Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109; hDepartment of Immunology, University of Texas MD Anderson Cancer Center, Houston, TX 77030; and iDepartment of Genetics, University of Texas MD Anderson Cancer Center, Houston, TX 77030 Contributed by Nancy A. Jenkins, July 23, 2017 (sent for review April 3, 2017; reviewed by Roland Rad and Kosuke Yusa) Epithelial ovarian cancer (EOC) is a deadly cancer, and its prognosis has To overcome this problem, several alternative methods have re- not been changed significantly during several decades. To seek new cently been used for cancer gene discovery, including insertional therapeutic targets for EOC, we performed an in vivo dropout screen mutagenesis and RNAi/shRNA/CRISPR/Cas9-based screens. -
RANBP1 (NM 002882) Human Recombinant Protein – TP323305 | Origene
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 TP323305 RANBP1 (NM_002882) Human Recombinant Protein Product data: Product Type: Recombinant Proteins Description: Recombinant protein of human RAN binding protein 1 (RANBP1) Species: Human Expression Host: HEK293T Tag: C-Myc/DDK Predicted MW: 23.1 kDa Concentration: >50 ug/mL as determined by microplate BCA method Purity: > 80% as determined by SDS-PAGE and Coomassie blue staining Buffer: 25 mM Tris.HCl, pH 7.3, 100 mM glycine, 10% glycerol Preparation: Recombinant protein was captured through anti-DDK affinity column followed by conventional chromatography steps. Storage: Store at -80°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_002873 Locus ID: 5902 UniProt ID: P04049, P43487, L7RRS6, A0A140VK94 RefSeq Size: 884 Cytogenetics: 22q11.21 RefSeq ORF: 603 Synonyms: HTF9A Summary: This gene encodes a protein that forms a complex with Ras-related nuclear protein (Ran) and metabolizes guanoside triphosphate (GTP). This complex participates in the regulation of the cell cycle by controlling transport of proteins and nucleic acids into the nucleus. There are multiple pseudogenes for this gene on chromosomes 9, 12, 17, and X. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013] 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 RANBP1 (NM_002882) Human Recombinant Protein – TP323305 Product images: Coomassie blue staining of purified RANBP1 protein (Cat# TP323305).