Viral Subversion of the Nuclear Pore Complex
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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. -
Nuclear Pore Proteins and the Control of Genome Functions
Downloaded from genesdev.cshlp.org on September 30, 2021 - Published by Cold Spring Harbor Laboratory Press REVIEW Nuclear pore proteins and the control of genome functions Arkaitz Ibarra and Martin W. Hetzer Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037, USA Nuclear pore complexes (NPCs) are composed of several Cytoplasmic filaments are mainly formed by Nup358/ copies of ~30 different proteins called nucleoporins (Nups). RanBP2, Nup214, and Nup88, while the nuclear basket is NPCs penetrate the nuclear envelope (NE) and regulate the composed of Nup153 and Tpr (Fig. 1; for Nup othologs, see nucleocytoplasmic trafficking of macromolecules. Beyond Rothballer and Kutay 2012). this vital role, NPC components influence genome func- The selective access of regulatory factors into the tions in a transport-independent manner. Nups play an nucleus and export of specific RNA molecules mediated evolutionarily conserved role in gene expression regulation by the NPC is required for the accurate progression of most that, in metazoans, extends into the nuclear interior. major cellular processes. However, our perception of Additionally, in proliferative cells, Nups play a crucial role the NPC components is rapidly evolving, as accumulating in genome integrity maintenance and mitotic progression. evidence indicates that they can also directly impact Here we discuss genome-related functions of Nups and DNA metabolism by genome-related functions (Liang their impact on essential DNA metabolism processes such and Hetzer 2011). Among these, one of the most remark- as transcription, chromosome duplication, and segregation. able and well-conserved roles of Nups is to associate with specific target genes to regulate their transcriptional activity (Casolari et al. -
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. -
Supplemental Material
Supplemental Table B ARGs in alphabetical order Symbol Title 3 months 6 months 9 months 12 months 23 months ANOVA Direction Category 38597 septin 2 1557 ± 44 1555 ± 44 1579 ± 56 1655 ± 26 1691 ± 31 0.05219 up Intermediate 0610031j06rik kidney predominant protein NCU-G1 491 ± 6 504 ± 14 503 ± 11 527 ± 13 534 ± 12 0.04747 up Early Adult 1G5 vesicle-associated calmodulin-binding protein 662 ± 23 675 ± 17 629 ± 16 617 ± 20 583 ± 26 0.03129 down Intermediate A2m alpha-2-macroglobulin 262 ± 7 272 ± 8 244 ± 6 290 ± 7 353 ± 16 0.00000 up Midlife Aadat aminoadipate aminotransferase (synonym Kat2) 180 ± 5 201 ± 12 223 ± 7 244 ± 14 275 ± 7 0.00000 up Early Adult Abca2 ATP-binding cassette, sub-family A (ABC1), member 2 958 ± 28 1052 ± 58 1086 ± 36 1071 ± 44 1141 ± 41 0.05371 up Early Adult Abcb1a ATP-binding cassette, sub-family B (MDR/TAP), member 1A 136 ± 8 147 ± 6 147 ± 13 155 ± 9 185 ± 13 0.01272 up Midlife Acadl acetyl-Coenzyme A dehydrogenase, long-chain 423 ± 7 456 ± 11 478 ± 14 486 ± 13 512 ± 11 0.00003 up Early Adult Acadvl acyl-Coenzyme A dehydrogenase, very long chain 426 ± 14 414 ± 10 404 ± 13 411 ± 15 461 ± 10 0.01017 up Late Accn1 amiloride-sensitive cation channel 1, neuronal (degenerin) 242 ± 10 250 ± 9 237 ± 11 247 ± 14 212 ± 8 0.04972 down Late Actb actin, beta 12965 ± 310 13382 ± 170 13145 ± 273 13739 ± 303 14187 ± 269 0.01195 up Midlife Acvrinp1 activin receptor interacting protein 1 304 ± 18 285 ± 21 274 ± 13 297 ± 21 341 ± 14 0.03610 up Late Adk adenosine kinase 1828 ± 43 1920 ± 38 1922 ± 22 2048 ± 30 1949 ± 44 0.00797 up Early -
Product Data Sheet Purified Anti-NUP153
Version: 2 Revision Date: 2016-01-08 Product Data Sheet Purified anti-NUP153 Catalog # / Size: 906201 / 100 µl Previously: Covance Catalog# MMS-102P Clone: QE5 Isotype: Mouse IgG1 Immunogen: The QE5 monoclonal antibody was generated against rat liver nuclear envelope proteins. Reactivity: Eukaryote Preparation: The antibody was purified by affinity chromatography. Formulation: Phosphate-buffered solution + 0.03% thimerosal. Concentration: 1 mg/ml Storage: The antibody solution should be stored undiluted between 2°C and 8°C. Please note the storage condition for this antibody has been changed from -20°C to between 2°C and 8°C. You can also check your vial or your Methanol fixed HeLa stained with the CoA to find the most accurate storage condition for this antibody. antibody QE5. This antibody brilliantly highlights the nuclear membrane (green). The golgi is stained with the Applications: antibody to Giantin. Applications: ICC, WB, IF, IP IEM - Reported in literature Recommended Usage: Each lot of this antibody is quality control tested by Immunocytochemistry. The optimal working dilution should be determined for each specific assay condition. • WB: 1:500* • IF: 1:250 • IP: 1:50 Application Notes: This antibody is effective in immunoblotting, immunofluorescence (IF) and immunoprecipitation (IP). *Predicted MW = 250 kD This antibody recognizes NUP153 as well as two related nuclear pore complex proteins: NUP214 and p62. By immunofluorescence, QE5 labels the nuclear envelope of eukaryotic cells giving a punctate staining pattern. Application References: 1. Pare GC, Easlick JL, Mislow JM, McNally EM, Kapiloff MS. Nesprin-1alpha contributes to the targeting of mAKAP to the cardiac myocyte nuclear envelope. -
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. -
Antigen-Specific Memory CD4 T Cells Coordinated Changes in DNA
Downloaded from http://www.jimmunol.org/ by guest on September 24, 2021 is online at: average * The Journal of Immunology The Journal of Immunology published online 18 March 2013 from submission to initial decision 4 weeks from acceptance to publication http://www.jimmunol.org/content/early/2013/03/17/jimmun ol.1202267 Coordinated Changes in DNA Methylation in Antigen-Specific Memory CD4 T Cells Shin-ichi Hashimoto, Katsumi Ogoshi, Atsushi Sasaki, Jun Abe, Wei Qu, Yoichiro Nakatani, Budrul Ahsan, Kenshiro Oshima, Francis H. W. Shand, Akio Ametani, Yutaka Suzuki, Shuichi Kaneko, Takashi Wada, Masahira Hattori, Sumio Sugano, Shinichi Morishita and Kouji Matsushima J Immunol Submit online. Every submission reviewed by practicing scientists ? is published twice each month by Author Choice option Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts http://jimmunol.org/subscription Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Freely available online through http://www.jimmunol.org/content/suppl/2013/03/18/jimmunol.120226 7.DC1 Information about subscribing to The JI No Triage! Fast Publication! Rapid Reviews! 30 days* Why • • • Material Permissions Email Alerts Subscription Author Choice Supplementary The Journal of Immunology The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2013 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. This information is current as of September 24, 2021. Published March 18, 2013, doi:10.4049/jimmunol.1202267 The Journal of Immunology Coordinated Changes in DNA Methylation in Antigen-Specific Memory CD4 T Cells Shin-ichi Hashimoto,*,†,‡ Katsumi Ogoshi,* Atsushi Sasaki,† Jun Abe,* Wei Qu,† Yoichiro Nakatani,† Budrul Ahsan,x Kenshiro Oshima,† Francis H. -
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. -
Destabilization of Ran C-Terminus Promotes GTP Loading and Occurs
bioRxiv preprint doi: https://doi.org/10.1101/305177; this version posted April 20, 2018. 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-ND 4.0 International license. Destabilization of Ran C-terminus promotes GTP loading and occurs in multiple Ran cancer mutations Yuqing Zhang1#, Jinhan Zhou1#, Yuping Tan1, Qiao Zhou1, Aiping Tong1, Xiaofei Shen1,2, Da Jia1,2, Xiaodong Sun3, Qingxiang Sun1* 1Department of Pathology and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China 2Key Laboratory of Birth Defects and Related Diseases of Women and Children, Department of Paediatrics, Division of Neurology, West China Second University Hospital, Sichuan University, Chengdu 610041, China 3 Department of Pharmacology, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu 610041, China #Equal contribution *Corresponding author: [email protected] Abstract Ran (Ras-related nuclear protein) plays several important roles in nucleo-cytoplasmic transport, mitotic spindle formation, nuclear envelope/nuclear pore complex assembly, and other diverse functions in the cytoplasm, as well as in cellular transformation when activated. Unlike other Ras superfamily proteins, Ran contains an auto-inhibitory C-terminal tail, which packs against its G domain and bias Ran towards binding GDP over GTP. The biological importance of this C- terminal tail is not well understood. By disrupting the interaction between the C-terminus and the G domain, we were able to generate Ran mutants that are innately active and potently bind to RanBP1 (Ran Binding Protein 1), nuclear export factor CRM1 and nuclear import factor KPNB1. -
The Role of Nucleoporin Elys in Nuclear Pore Complex Assembly and Regulation of Genome Architecture
International Journal of Molecular Sciences Review The Role of Nucleoporin Elys in Nuclear Pore Complex Assembly and Regulation of Genome Architecture Yuri Y. Shevelyov Department of Molecular Genetics of Cell, Institute of Molecular Genetics of National Research Centre “Kurchatov Institute”, 123182 Moscow, Russia; [email protected]; Tel.: +7-499-196-0809 Received: 29 November 2020; Accepted: 11 December 2020; Published: 13 December 2020 Abstract: For a long time, the nuclear lamina was thought to be the sole scaffold for the attachment of chromosomes to the nuclear envelope (NE) in metazoans. However, accumulating evidence indicates that nuclear pore complexes (NPCs) comprised of nucleoporins (Nups) participate in this process as well. One of the Nups, Elys, initiates NPC reassembly at the end of mitosis. Elys directly binds the decondensing chromatin and interacts with the Nup107–160 subcomplex of NPCs, thus serving as a seeding point for the subsequent recruitment of other NPC subcomplexes and connecting chromatin with the re-forming NE. Recent studies also uncovered the important functions of Elys during interphase where it interacts with chromatin and affects its compactness. Therefore, Elys seems to be one of the key Nups regulating chromatin organization. This review summarizes the current state of our knowledge about the participation of Elys in the post-mitotic NPC reassembly as well as the role that Elys and other Nups play in the maintenance of genome architecture. Keywords: nucleoporin; Elys; Mel-28; NPC; nuclear envelope; genome architecture; chromatin 1. Introduction In eukaryotic cells, the nuclear-cytoplasmic transport of macromolecules occurs through channels in the nuclear envelope (NE) formed by nuclear pore complexes (NPCs). -
Autoantibodies and Anti-Microbial Antibodies
bioRxiv preprint doi: https://doi.org/10.1101/403519; this version posted August 29, 2018. 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 4.0 International license. Autoantibodies and anti-microbial antibodies: Homology of the protein sequences of human autoantigens and the microbes with implication of microbial etiology in autoimmune diseases Peilin Zhang, MD., Ph.D. PZM Diagnostics, LLC Charleston, WV 25301 Correspondence: Peilin Zhang, MD., Ph.D. PZM Diagnostics, LLC. 500 Donnally St., Suite 303 Charleston, WV 25301 Email: [email protected] Tel: 304 444 7505 1 bioRxiv preprint doi: https://doi.org/10.1101/403519; this version posted August 29, 2018. 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 4.0 International license. Abstract Autoimmune disease is a group of diverse clinical syndromes with defining autoantibodies within the circulation. The pathogenesis of autoantibodies in autoimmune disease is poorly understood. In this study, human autoantigens in all known autoimmune diseases were examined for the amino acid sequences in comparison to the microbial proteins including bacterial and fungal proteins by searching Genbank protein databases. Homologies between the human autoantigens and the microbial proteins were ranked high, medium, and low based on the default search parameters at the NCBI protein databases. Totally 64 human protein autoantigens important for a variety of autoimmune diseases were examined, and 26 autoantigens were ranked high, 19 ranked medium to bacterial proteins (69%) and 27 ranked high and 16 ranked medium to fungal proteins (66%) in their respective amino acid sequence homologies. -
Distinct Ranbp1 Nuclear Export and Cargo Dissociation Mechanisms
RESEARCH ARTICLE Distinct RanBP1 nuclear export and cargo dissociation mechanisms between fungi and animals Yuling Li1†, Jinhan Zhou1†, Sui Min1†, Yang Zhang2, Yuqing Zhang1, Qiao Zhou1, Xiaofei Shen3, Da Jia3, Junhong Han2, Qingxiang Sun1* 1Department of Pathology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Collaborative Innovation Centre of Biotherapy, Chengdu, China; 2Division of Abdominal Cancer, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Collaborative Innovation Centre for Biotherapy, Chengdu, China; 3Key Laboratory of Birth Defects and Related Diseases of Women and Children, Department of Paediatrics, Division of Neurology, West China Second University Hospital, Sichuan University, Chengdu, China Abstract Ran binding protein 1 (RanBP1) is a cytoplasmic-enriched and nuclear-cytoplasmic shuttling protein, playing important roles in nuclear transport. Much of what we know about RanBP1 is learned from fungi. Intrigued by the long-standing paradox of harboring an extra NES in animal RanBP1, we discovered utterly unexpected cargo dissociation and nuclear export mechanisms for animal RanBP1. In contrast to CRM1-RanGTP sequestration mechanism of cargo dissociation in fungi, animal RanBP1 solely sequestered RanGTP from nuclear export complexes. In fungi, RanBP1, CRM1 and RanGTP formed a 1:1:1 nuclear export complex; in contrast, animal RanBP1, CRM1 and RanGTP formed a 1:1:2 nuclear export complex. The key feature for the two mechanistic changes from fungi to animals was the loss of affinity between RanBP1-RanGTP and *For correspondence: CRM1, since residues mediating their interaction in fungi were not conserved in animals. The [email protected] biological significances of these different mechanisms in fungi and animals were also studied.