T-Cell Receptor (TCR) Signaling Promotes the Assembly of Ranbp2
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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. -
SUMO-1 Regulates the Conformational Dynamics of Thymine-DNA
Smet-Nocca et al. BMC Biochemistry 2011, 12:4 http://www.biomedcentral.com/1471-2091/12/4 RESEARCHARTICLE Open Access SUMO-1 regulates the conformational dynamics of Thymine-DNA Glycosylase regulatory domain and competes with its DNA binding activity Caroline Smet-Nocca1, Jean-Michel Wieruszeski2, Hélène Léger1,3, Sebastian Eilebrecht1,3, Arndt Benecke1,3* Abstract Background: The human thymine-DNA glycosylase (TDG) plays a dual role in base excision repair of G:U/T mismatches and in transcription. Regulation of TDG activity by SUMO-1 conjugation was shown to act on both functions. Furthermore, TDG can interact with SUMO-1 in a non-covalent manner. Results: Using NMR spectroscopy we have determined distinct conformational changes in TDG upon either covalent sumoylation on lysine 330 or intermolecular SUMO-1 binding through a unique SUMO-binding motif (SBM) localized in the C-terminal region of TDG. The non-covalent SUMO-1 binding induces a conformational change of the TDG amino-terminal regulatory domain (RD). Such conformational dynamics do not exist with covalent SUMO-1 attachment and could potentially play a broader role in the regulation of TDG functions for instance during transcription. Both covalent and non-covalent processes activate TDG G:U repair similarly. Surprisingly, despite a dissociation of the SBM/SUMO-1 complex in presence of a DNA substrate, SUMO-1 preserves its ability to stimulate TDG activity indicating that the non-covalent interactions are not directly involved in the regulation of TDG activity. SUMO-1 instead acts, as demonstrated here, indirectly by competing with the regulatory domain of TDG for DNA binding. -
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. -
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. -
The Nuclear Export Factor CRM1 Controls Juxta-Nuclear Microtubule-Dependent Virus Transport I-Hsuan Wang1,*,‡, Christoph J
© 2017. Published by The Company of Biologists Ltd | Journal of Cell Science (2017) 130, 2185-2195 doi:10.1242/jcs.203794 RESEARCH ARTICLE The nuclear export factor CRM1 controls juxta-nuclear microtubule-dependent virus transport I-Hsuan Wang1,*,‡, Christoph J. Burckhardt1,2,‡, Artur Yakimovich1,‡, Matthias K. Morf1,3 and Urs F. Greber1,§ ABSTRACT directly bind to virions, or move virions in endocytic or secretory Transport of large cargo through the cytoplasm requires motor vesicles (Greber and Way, 2006; Marsh and Helenius, 2006; proteins and polarized filaments. Viruses that replicate in the nucleus Yamauchi and Greber, 2016). While short-range transport of virions of post-mitotic cells use microtubules and the dynein–dynactin motor often depends on actin and myosin motors (Taylor et al., 2011), to traffic to the nuclear membrane and deliver their genome through long-range cytoplasmic transport requires microtubules, and, in the nuclear pore complexes (NPCs) into the nucleus. How virus particles case of incoming virions, the minus-end-directed motor complex – (virions) or cellular cargo are transferred from microtubules to the dynein dynactin (Dodding and Way, 2011; Hsieh et al., 2010). NPC is unknown. Here, we analyzed trafficking of incoming Like cellular cargo, viruses engage in bidirectional motor- cytoplasmic adenoviruses by single-particle tracking and super- dependent motility by recruiting cytoskeletal motors of opposite resolution microscopy. We provide evidence for a regulatory role of directionality (Greber and Way, 2006; Scherer and Vallee, 2011; CRM1 (chromosome-region-maintenance-1; also known as XPO1, Welte, 2004). The net transport balance of a cargo is determined at exportin-1) in juxta-nuclear microtubule-dependent adenovirus the level of motor recruitment, motor coordination and the tug-of- transport. -
Original Article Epithelioid Inflammatory Myofibroblastic Sarcoma of Stomach: Diagnostic Pitfalls and Clinical Characteristics
Int J Clin Exp Pathol 2019;12(5):1738-1744 www.ijcep.com /ISSN:1936-2625/IJCEP0092254 Original Article Epithelioid inflammatory myofibroblastic sarcoma of stomach: diagnostic pitfalls and clinical characteristics Pei Xu1, Pingping Shen2, Yangli Jin3, Li Wang4, Weiwei Wu1 1Department of Burns, Ningbo Huamei Hospital, University of Chinese Academy of Science (Ningbo No. 2 Hospital), Ningbo, China; Departments of 2Gastroenterology, 3Ultrasonography, Yinzhou Second Hospital, Ningbo, China; 4Department of Pathology, Clinical Pathological Diagnosis Center, Ningbo, China Received February 3, 2019; Accepted February 26, 2019; Epub May 1, 2019; Published May 15, 2019 Abstract: Inflammatory myofibroblastic tumor (IMT) is a neoplasm composed of spindled neoplastic myofibroblasts admixed with reactive lymphoplasmacytic cells, plasma cells, and/or eosinophils, which has an intermediate bio- logical behavior. An IMT variant with plump round epithelioid or histiocytoid tumor cells, recognized as epithelioid inflammatory myofibroblastic sarcoma (EIMS), has a more clinically aggressive progression. To the best of our knowl- edge, only about 40 cases of EIMS have previously been reported in limited literature. Here, we report here a case of unusual EIMS with a relative indolent clinical behavior. We reviewed the literature for 18 similar cases. The patients present with a highly aggressive inflammatory myofibroblastic tumor characterized by round or epithelioid morphol- ogy, prominent neutrophilic infiltrate, and positive staining of ALK with RANBP2-ALK gene fusion or RANBP1-ALK gene fusion, or EML4-ALK gene fusion. Our case is the first case of primary stomach EIMS. Moreover, the mecha- nisms of the rare entity have not been widely recognized and require further study. Early accurate diagnosis and complete resection of this tumor is necessary. -
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. -
Atlas of Genetics and Cytogenetics in Oncology and Haematology
Atlas of Genetics and Cytogenetics in Oncology and Haematology The nuclear pore complex becomes alive: new insights into its dynamics and involvement in different cellular processes Joachim Köser*, Bohumil Maco*, Ueli Aebi, and Birthe Fahrenkrog M.E. Müller Institute for Structural Biology, Biozentrum, University of Basel, Klingelbergstr. 70, CH-4056 Basel, Switzerland Running title: NPC becomes alive * authors contributed equally corresponding author: [email protected]; phone: +41 61 267 2255; fax: +41 61 267 2109 Atlas Genet Cytogenet Oncol Haematol 2005; 2 -347- Abstract In this review we summarize the structure and function of the nuclear pore complex (NPC). Special emphasis is put on recent findings which reveal the NPC as a dynamic structure in the context of cellular events like nucleocytoplasmic transport, cell division and differentiation, stress response and apoptosis. Evidence for the involvement of nucleoporins in transcription and oncogenesis is discussed, and evolutionary strategies developed by viruses to cross the nuclear envelope are presented. Keywords: nucleus; nuclear pore complex; nucleocytoplasmic transport; nuclear assembly; apoptosis; rheumatoid arthritis; primary biliary cirrhosis (PBC); systemic lupus erythematosus; cancer 1. Introduction Eukaryotic cells in interphase are characterized by distinct nuclear and cytoplasmic compartments separated by the nuclear envelope (NE), a double membrane that is continuous with the endoplasmic reticulum (ER). Nuclear pore complexes (NPCs) are large supramolecular assemblies embedded in the NE and they provide the sole gateways for molecular trafficking between the cytoplasm and nucleus of interphase eukaryotic cells. They allow passive diffusion of ions and small molecules, and facilitate receptor-mediated transport of signal bearing cargoes, such as proteins, RNAs and ribonucleoprotein (RNP) particles (Görlich and Kutay, 1999; Conti and Izaurralde, 2001; Macara, 2001; Fried and Kutay, 2003). -
UBC9 (UBE2I) Antibody (N-Term) Purified Rabbit Polyclonal Antibody (Pab) Catalog # Ap1064a
10320 Camino Santa Fe, Suite G San Diego, CA 92121 Tel: 858.875.1900 Fax: 858.622.0609 UBC9 (UBE2I) Antibody (N-term) Purified Rabbit Polyclonal Antibody (Pab) Catalog # AP1064a Specification UBC9 (UBE2I) Antibody (N-term) - Product Information Application WB, IHC-P,E Primary Accession P63279 Other Accession P63282, P63281, P63280, P63283, Q9DDJ0, Q9W6H5 Reactivity Human Predicted Zebrafish, Chicken, Mouse, Rat, Xenopus Host Rabbit Clonality Polyclonal Isotype Rabbit Ig Antigen Region 1-30 Western blot analysis of anti-UBE2I Antibody (N-term) (Cat.#AP1064a) in A2058 cell line UBC9 (UBE2I) Antibody (N-term) - Additional lysates (35ug/lane). UBE2I(arrow) was Information detected using the purified Pab. Gene ID 7329 Other Names SUMO-conjugating enzyme UBC9, 632-, SUMO-protein ligase, Ubiquitin carrier protein 9, Ubiquitin carrier protein I, Ubiquitin-conjugating enzyme E2 I, Ubiquitin-protein ligase I, p18, UBE2I, UBC9, UBCE9 Target/Specificity This UBC9 (UBE2I) antibody is generated from rabbits immunized with a KLH conjugated synthetic peptide between 1-30 amino acids from the N-terminal region of Western blot analysis of UBE2I (arrow) using human UBC9 (UBE2I). rabbit polyclonal UBE2I Antibody (S7) (Cat.#AP1064a). 293 cell lysates (2 ug/lane) Dilution either nontransfected (Lane 1) or transiently WB~~1:1000 transfected (Lane 2) with the UBE2I gene. IHC-P~~1:50~100 Format Purified polyclonal antibody supplied in PBS with 0.09% (W/V) sodium azide. This antibody is prepared by Saturated Ammonium Sulfate (SAS) precipitation followed by dialysis against PBS. Page 1/3 10320 Camino Santa Fe, Suite G San Diego, CA 92121 Tel: 858.875.1900 Fax: 858.622.0609 Storage Maintain refrigerated at 2-8°C for up to 2 weeks. -
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. -
The E3 Ligase PIAS1 Regulates P53 Sumoylation to Control Stress-Induced Apoptosis of Lens
fcell-09-660494 June 14, 2021 Time: 13:5 # 1 ORIGINAL RESEARCH published: 14 June 2021 doi: 10.3389/fcell.2021.660494 The E3 Ligase PIAS1 Regulates p53 Sumoylation to Control Stress-Induced Apoptosis of Lens Edited by: Wolfgang Knabe, Epithelial Cells Through the Universität Münster, Germany Proapoptotic Regulator Bax Reviewed by: Guillaume Bossis, † † † † † Centre National de la Recherche Qian Nie , Huimin Chen , Ming Zou , Ling Wang , Min Hou , Jia-Wen Xiang, Scientifique (CNRS), France Zhongwen Luo, Xiao-Dong Gong, Jia-Ling Fu, Yan Wang, Shu-Yu Zheng, Yuan Xiao, Stefan Müller, Yu-Wen Gan, Qian Gao, Yue-Yue Bai, Jing-Miao Wang, Lan Zhang, Xiang-Cheng Tang, Goethe University Frankfurt, Germany Xuebin Hu, Lili Gong, Yizhi Liu* and David Wan-Cheng Li*‡ Leena Latonen, University of Eastern Finland, Finland State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China *Correspondence: David Wan-Cheng Li Protein sumoylation is one of the most important post-translational modifications [email protected] Yizhi Liu regulating many biological processes (Flotho A & Melchior F. 2013. Ann Rev. Biochem. [email protected] 82:357–85). Our previous studies have shown that sumoylation plays a fundamental †These authors have contributed role in regulating lens differentiation (Yan et al., 2010. PNAS, 107(49):21034-9.; equally to this work Gong et al., 2014. PNAS. 111(15):5574–9). Whether sumoylation is implicated in lens ‡ ORCID: David Wan-Cheng Li pathogenesis remains elusive. Here, we present evidence to show that the protein orcid.org/0000-0002-7398-7630 inhibitor of activated STAT-1 (PIAS1), a E3 ligase for sumoylation, is implicated in regulating stress-induced lens pathogenesis.