PP2A-Dependent Disruption of Centrosome Replication and Cytoskeleton Organization in Drosophila by SV40 Small Tumor Antigen
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Enhanced Expression of Vascular Endothelial Growth Factor (VEGF) Plays a Critical Role in the Tumor Progression Potential Induced by Simian Virus 40 Large T Antigen
Oncogene (2002) 21, 2896 ± 2900 ã 2002 Nature Publishing Group All rights reserved 0950 ± 9232/02 $25.00 www.nature.com/onc Enhanced expression of vascular endothelial growth factor (VEGF) plays a critical role in the tumor progression potential induced by simian virus 40 large T antigen Alfonso Catalano1, Mario Romano*,2, Stefano Martinotti3 and Antonio Procopio*,1 1Institute of Experimental Pathology, University of Ancona, Faculty of Medicine, Via Ranieri, 60131 Ancona, Italy; 2Department of Human Pathology, University of Messina, 98125 Messina, Italy; 3Department of Oncology and Neuroscience, `G. D'Annunzio' University, Chieti, Italy Vascular endothelial growth factor (VEGF), an impor- disorders, including mesotheliomas (Kumar-Singh et tant angiogenic factor, regulates cell proliferation, al., 1999). Among these, VEGF, whose crucial role in dierentiation, and apoptosis through activation of its tumor angiogenesis is well established (Hanahan and tyrosine-kinase receptors, such as Flt-1 and Flk-1/Kdr. Folkman., 1996), acts also as a potent mitogen and Human malignant mesothelioma cells (HMC), which survival factor for human malignant mesothelioma have wild-type p53, express VEGF and exhibit cell cells (HMC). In fact, VEGF regulates HMC prolifera- growth increased by VEGF. Here, we demonstrate that tion through its tyrosine-kinase receptors activation early transforming proteins of simian virus (SV) 40, large (i.e. Flt-1 and KDR/¯k-1) (Strizzi et al., 2001). In tumor antigen (Tag) and small tumor antigen (tag), addition, VEGF is the main eector of 5-lipoxygenase which have been associated with mesotheliomas, en- action on HMC survival (Romano et al., 2001). Thus, hanced HMC proliferation by inducing VEGF expres- VEGF plays a key role by regulating multiple sion. -
Oncogenes of DNA Tumor Viruses1
[CANCER RESEARCH 48. 493-496. February I. 1988] Perspectives in Cancer Research Oncogenes of DNA Tumor Viruses1 Arnold J. Levine Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544 Experiments carried out over the past 10-12 years have the cellular oncogenes. It will attempt to identify where more created a field or approach which may properly be termed the information is required or contradictions appear in the devel molecular basis of cancer. One of its major accomplishments oping concepts. Finally, this communication will examine ex has been the identification and understanding of some of the amples of cooperation between oncogenes and other gene prod functions of a group of cancer-causing genes, the oncogenes. ucts which modify the mode of action of the former. If we are The major path to the oncogenes came from the study of cancer- on the right track, then general principles may well emerge. causing viruses. The oncogenes have been recognized and stud Tumor formation in animals or transformation in cell culture ied by two separate but related groups of virologists focusing has been demonstrated with many different DNA-containing upon either the DNA (1) or RNA (2) tumor viruses (they even viruses (1). In most cases it has been possible to identify one or have separate meetings now that these fields have grown so a few viral genes and their products that are responsible for large). From their studies it has become clear that the oncogenes transformation or, in some cases, tumorigenesis. A list of these of each virus type have very different origins. -
Tätigkeitsbericht 2007/2008
Tätigkeitsbericht 2007/2008 8 200 / 7 0 20 Tätigkeitsbericht Stiftung bürgerlichen Rechts Martinistraße 52 · 20251 Hamburg Tel.: +49 (0) 40 480 51-0 · Fax: +49 (0) 40 480 51-103 [email protected] · www.hpi-hamburg.de Impressum Verantwortlich Prof. Dr. Thomas Dobner für den Inhalt Dr. Heinrich Hohenberg Redaktion Dr. Angela Homfeld Dr. Nicole Nolting Grafik & Layout AlsterWerk MedienService GmbH Hamburg Druck Hartung Druck + Medien GmbH Hamburg Titelbild Neu gestaltete Fassade des Seuchenlaborgebäudes Tätigkeitsbericht 2007/2008 Heinrich-Pette-Institut für Experimentelle Virologie und Immunologie an der Universität Hamburg Martinistraße 52 · 20251 Hamburg Postfach 201652 · 20206 Hamburg Telefon: +49-40/4 80 51-0 Telefax: +49-40/4 80 51-103 E-Mail: [email protected] Internet: www.hpi-hamburg.de Das Heinrich-Pette-Institut ist Mitglied der Leibniz-Gemeinschaft (WGL) Internet: www.wgl.de Inhaltsverzeichnis Allgemeiner Überblick Vorwort ................................................................................................... 1 Die Struktur des Heinrich-Pette-Instituts .............................................. 2 Modernisierung des HPI erfolgreich abgeschlossen ............................ 4 60 Jahre HPI .............................................................................................. 5 Offen für den Dialog .............................................................................. 6 Preisverleihungen und Ehrungen .......................................................... 8 Personelle Veränderungen in -
Inhibition of HIV-1 by an Anti-Integrase Single-Chain Variable
Gene Therapy (1999) 6, 660–666 1999 Stockton Press All rights reserved 0969-7128/99 $12.00 http://www.stockton-press.co.uk/gt Inhibition of HIV-1 by an anti-integrase single-chain variable fragment (SFv): delivery by SV40 provides durable protection against HIV-1 and does not require selection M BouHamdan1, L-X Duan1, RJ Pomerantz1 and DS Strayer1,2 1The Dorrance H Hamilton Laboratories, Center for Human Virology, Division of Infectious Diseases, Department of Medicine; and 2Department of Pathology, Anatomy and Cell Biology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA, USA Human immunodeficiency virus type I (HIV-1) encodes the SFv-IN was confirmed by Western blotting and several proteins that are packaged into virus particles. Inte- immunofluorescence staining, which showed that Ͼ90% of grase (IN) is an essential retroviral enzyme, which has SupT1 T-lymphocytic cells treated with SV(Aw) expressed been a target for developing agents to inhibit virus repli- the SFv-IN protein without selection. When challenged, cation. In previous studies, we showed that intracellular HIV-1 replication, as measured by HIV-1 p24 antigen expression of single-chain variable antibody fragments expression and syncytium formation, was potently inhibited (SFvs) that bind IN, delivered via retroviral expression vec- in cells expressing SV40-delivered SFv-IN. Levels of inhi- tors, provided resistance to productive HIV-1 infection in bition of HIV-1 infection achieved using this approach were T-lymphocytic cells. In the current studies, we evaluated comparable to those achieved using murine leukemia virus simian-virus 40 (SV40) as a delivery vehicle for anti-IN (MLV) as a transduction vector, the major difference being therapy of HIV-1 infection. -
A Polyoma Mutant That Encodessmall T Antigen but Not Middle T Antigen
MOLECULAR AND CELLULAR BIOLOGY, Dec. 1984, p. 2774-2783 Vol. 4, No. 12 0270-7306/84/122774-10$02.00/0 Copyright © 1984, American Society for Microbiology A Polyoma Mutant That Encodes Small T Antigen But Not Middle T Antigen Demonstrates Uncoupling of Cell Surface and Cytoskeletal Changes Associated with Cell Transformation T. JAKE LIANG, GORDON G. CARMICHAEL,t AND THOMAS L. BENJAMIN* Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115 Received 2 July 1984/Accepted 31 August 1984 The hr-t gene of polyoma virus encodes both the small and middle T (tumor) antigens and exerts pleiotropic effects on cells. By mutating the 3' splice site for middle T mRNA, we have constructed a virus mutant, Py8O8A, which fails to express middle T but encodes normal small and large T proteins. The mutant failed to induce morphological transformation or growth in soft agar, but did stimulate postconfluent growth of normal cells. Cells infected by Py8O8A became fully agglutinable by lectins while retaining normal actin cable architecture and normal levels of extracellular fibronectin. These properties of Py8O8A demonstrated the separability of structural changes at the cell surface from those in the cytoskeleton and extracellular matrix, parameters which have heretofore been linked in the action of the hr-t and other viral oncogenes. The early region of polyoma encodes three proteins de- substitution of phenylalanine for tyrosine at position 315 in tected as tumor (T) antigens. These polypeptides of 100,000 middle T has been made and studied in two laboratories, daltons (100K; large T), 56K (middle T), and 22K (small T) with different results. -
Hepatitis B Virus X Protein Inhibits P53 Sequence-Specific DNA Binding
Proc. Nati. Acad. Sci. USA Vol. 91, pp. 2230-2234, March 1994 Medical Sciences Hepatitis B virus X protein inhibits p53 sequence-specific DNA binding, transcriptional activity, and association with transcription factor ERCC3 XIN WEI WANG*, KATHLEEN FORRESTER*, HEIDI YEH*, MARK A. FEITELSONt, JEN-REN GUI, AND CURTIS C. HARRIS*§ *Laboratory of Human Carcinogenesis, Division of Cancer Etiology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; tDepartment of Pathology and Cell Biology, Jefferson Medical College, Philadelphia, PA 19107; and tDepartment of Molecular Biology and Biochemistry, Shanghai Cancer Institute, Shanghai, People's Republic of China. Communicated by Bert Vogelstein, December 27, 1993 (receivedfor review December 9, 1993) ABSTRACT Chronic active hepatitis caused by infection about the role of HBX in HCC development. In this report, with hepatitis B virus, a DNA virus, is a major risk factor for we present results consistent with the hypothesis that HBX human hepatocellular carcinoma. Since the oncogenicity of binds to p53 and abrogates its normal cellular functions. several DNA viruses is dependent on the interaction of their viral oncoproteins with cellular tumor-suppressor gene prod- MATERIAL AND METHODS ucts, we investigated the interaction between hepatitis B virus X protein (HBX) and human wild-type p53 protein. HBX Plasmids. Plasmid constructs encoding GST-p53-WT, con- complexes with the wild-type p53 protein and inhibits its taining glutathione S-transferase (GST) fused to human wild- sequence-specific DNA binding in vitro. HBX expresslin also type p53, and GST-p53-135Y, containing GST fused to the inhibits p53-mediated transcrptional activation in vivo and the mutant p53 containing a His -* Tyr mutation at codon 135, in vitro asoition of p53 and ERCC3, a general transcription were provided by Jon Huibregtse (National Cancer Institute) factor involved in nucleotide excision repair. -
Review Article Human Polyomaviruses in Skin Diseases
SAGE-Hindawi Access to Research Pathology Research International Volume 2011, Article ID 123491, 12 pages doi:10.4061/2011/123491 Review Article Human Polyomaviruses in Skin Diseases Ugo Moens,1 Maria Ludvigsen,1 and Marijke Van Ghelue2 1 Institute of Medical Biology, Faculty of Health Sciences, University of Tromsø, 9037 Tromsø, Norway 2 Department of Medical Genetics, University Hospital of Northern-Norway, 9038 Tromsø, Norway Correspondence should be addressed to Ugo Moens, [email protected] Received 28 February 2011; Accepted 29 June 2011 Academic Editor: Gerardo Ferrara Copyright © 2011 Ugo Moens et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Polyomaviruses are a family of small, nonenveloped viruses with a circular double-stranded DNA genome of ∼5,000 base pairs protected by an icosahedral protein structure. So far, members of this family have been identified in birds and mammals. Until 2006, BK virus (BKV), JC virus (JCV), and simian virus 40 (SV40) were the only polyomaviruses known to circulate in the human population. Their occurrence in individuals was mainly confirmed by PCR and the presence of virus-specific antibodies. Using the same methods, lymphotropic polyomavirus, originally isolated in monkeys, was recently shown to be present in healthy individuals although with much lower incidence than BKV, JCV, and SV40. The use of advanced high-throughput sequencing and improved rolling circle amplification techniques have identified the novel human polyomaviruses KI, WU, Merkel cell polyomavirus, HPyV6, HPyV7, trichodysplasia spinulosa-associated polyomavirus, and HPyV9. -
(12) Patent Application Publication (10) Pub. No.: US 2004/0023207 A1 Polansky (43) Pub
US 20040023207A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2004/0023207 A1 Polansky (43) Pub. Date: Feb. 5, 2004 (54) ASSAYS FOR DRUG DISCOVERY BASED ON Publication Classification MICROCOMPETITION WITH A FOREIGN POLYNUCLEOTIDE (51) Int. Cl." .............................. C12O 1/70; C12O 1/68; C12N 15/85; C12N 15/86 (52) U.S. Cl. .................. 435/5; 435/6; 435/455; 435/456 (76) Inventor: Hanan Polansky, Rochester, NY (US) (57) ABSTRACT Correspondence Address: A recent discovery showed that microcompetition between a Hanan Polansky foreign polynucleotide and a cellular polynucleotide is a risk 3159 S. Winton Rd. factor for Some of the major chronic diseases. The invention Rochester, NY 14623 (US) uses this novel discovery to present assays for Screening compounds based on their effectiveness in modulating Such microcompetition. The effective compounds can be used in (21) Appl. No.: 10/211,295 treatment of these chronic diseases. The invention also presents assays for Screening compounds that can be used in treatment of chronic diseaseS resulting from other foreign (22) Filed: Aug. 1, 2002 polynucleotide-type disruptions. Patent Application Publication Feb. 5, 2004 Sheet 1 of 6 US 2004/0023207 A1 s e 2 9 s H c 2 4 competitor plasmid/test plasmid Figure 1 1 O 09% 1 2 3 4 competitor plasmid/test plasmid -H Ltk- (pSV2Neo) -A-ML (pSV2neo) . A- - - Ltk- (pA1 Oneo) - - - - - - Mill (pA1 Oneo) Figure 2 Patent Application Publication Feb. 5, 2004 Sheet 2 of 6 US 2004/0023207 A1 e 2 r U H c O s S 2 3. Molar ratio (pSV2NeolhMT-ilA-CAT) Figure 3 Patent Application Publication Feb. -
Tumor Antigen (Hybrid Trp-Lac Promoter/Actin Cable Effect) ILAN BIKEL*, THOMAS M
Proc. NatL Acad. Sci. USA Vol. 80, pp. 906-910, February 1983 Biochemistry Purification of biologically active simian virus 40 small tumor antigen (hybrid trp-lac promoter/actin cable effect) ILAN BIKEL*, THOMAS M. ROBERTS*, MARILUCI T. BLADON*, ROBERT GREEN*, EGON AMANNt, AND DAVID M. LIVINGSTON* *The Sidney Farber Cancer Institute and The Departments of Medicine and Pathology, Harvard Medical School, Boston, Massachusetts 02115; and tDepartment of Biochemistry and Molecular Biology, Harvard University, Cambridge, Massachusetts 02138 Communicated by Morris Friedkin, October 29, 1982 The simian virus 40 small tumor antigen (t antigen) gene has been were grown in L broth containing ampicillin (40 Ag/ml) to an cloned downstream from a hybrid Escherichia coli trp-lac pro- ODW of0.7 and then incubated for 2 hr with 5 mM isopropyl moter anda suitable ribosome binding site. Abacterial clone (865i) f3-D-thiogalactopyranoside. Radiolabeling of proteins with transformed by such a plasmid (pTR865) expresses this gene and, [3S]methionine was performed as described (31). under optimal conditions, can produce .5% ofits total protein as t Antigen and Protein Assays. t antigen was detected by Na- t antigen. Soluble extracts ofsuch a clone were relatively depleted DodSO4/polyacrylamide slab gel electrophoresis (32) using 4% in t antigen, which was found in the initial pellet fraction. The stacking and 15% separating gels. Marker proteins were bovine protein was recovered from this fraction in a significantly purified serum albumin (Mr 68,000), carbonic anhydrase (29,000), form byextraction with urea-containing buffer. After gel filtration concentrations were deter- of such t antigen-enriched solutions, highly purified protein was and myoglobin (17,000). -
The Simian Virus 40 Large Tumor Antigen Activates Csrc and Requires Csrc for Full Neoplastic Transformation
ANTICANCER RESEARCH 30: 47-54 (2010) The Simian Virus 40 Large Tumor Antigen Activates cSrc and Requires cSrc for Full Neoplastic Transformation ROZANNE ARULANANDAM, MULU GELETU and LEDA RAPTIS Departments of Microbiology and Immunology and Pathology, Queen's University, Kingston, Ontario, K7L 3N6, Canada Abstract. Aim: To investigate the role of the cellular The effects of TAg on the Rb family proteins are thought to be protooncogene product, cSrc, in neoplastic transformation by exerted by regulating the activity of the E2F transcription factors. the large tumor antigen of simian virus 40 (TAg), the ability of There are eight known E2F proteins (E2F1-8), all of which TAg to increase cSrc activity was examined. Materials and possess a DNA-binding domain that governs their interactions Methods: cSrc activity was measured in cells expressing wild- with a common consensus sequence present in the promoters of type or mutant TAg and compared to the parental line. Results: a number of genes (reviewed in (4, 5)). In quiescent cells, E2F- The results indicated that TAg expression in mouse 3T3 regulated genes are not expressed because their promoters are fibroblasts causes a dramatic increase in cSrc activity, a finding occupied primarily by p130/E2F4 complexes which repress which establishes TAg as a cSrc activator. This ability transcription. Following receptor stimulation, Rb proteins are depended upon a TAg, intact retinoblastoma-susceptibility gene inactivated through phosphorylation by the cyclin-dependent product (Rb) family-binding site. In addition, genetic ablation kinases and this results in the replacement of the p130/E2F4 of pRb in mouse fibroblasts increased cSrc activity, suggesting complexes by the ‘activating’ E2F1-3. -
Identification of Rab18 As an Essential Host Factor for Bkpyv Infection Using a Whole Genome RNA 2 Interference Screen
bioRxiv preprint doi: https://doi.org/10.1101/157602; this version posted June 29, 2017. 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. 1 Identification of Rab18 as an Essential Host Factor for BKPyV Infection Using a Whole Genome RNA 2 Interference Screen 3 4 Linbo Zhaoa, Michael J. Imperialea,b,* 5 6 aDepartment of Microbiology and Immunology, bComprehensive Cancer Center, University of Michigan, 7 Ann Arbor, MI, 48109, USA 8 9 10 11 12 13 14 15 16 17 18 * Corresponding author. Department of Microbiology and Immunology, 1150 West Medical Center 19 Drive, 5724 Medical Science II, Ann Arbor, MI 48109-5620, USA. Tel. +1 (734) 763 9162. Fax: +1 (734) 20 764 3562. 21 E-mail addresses: [email protected] (L. Zhao); [email protected] (M.J. Imperiale). 22 23 24 1 bioRxiv preprint doi: https://doi.org/10.1101/157602; this version posted June 29, 2017. 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. 25 Abstract 26 27 BK polyomavirus (BKPyV) is a human pathogen first isolated in 1971. BKPyV infection is ubiquitous in the 28 human population, with over 80% of adults worldwide being seropositive for BKPyV. BKPyV infection is 29 usually asymptomatic; however, BKPyV reactivation in immunosuppressed transplant patients causes 30 two diseases, polyomavirus-associated nephropathy and hemorrhagic cystitis. -
Interactions Between Polyomavirus Large T Antigen and the Viral Replication Origin Dna: How and Why
INTERACTIONS BETWEEN POLYOMAVIRUS LARGE T ANTIGEN AND THE VIRAL REPLICATION ORIGIN DNA: HOW AND WHY by Yu-Cai Peng Department of Microbiology and Immunology McGill University, Montreal April, 1999 A thesis submitted to the Faculty of Craduate Studies and Re3earch in partial fulfullmeat of the requirements of the degree of doctor of philosophy @Yu-Cai Peng, 1999 National Library Biblioth ue nationale 1+1 of Canada du Cana7 a Acquisitions and Acquisitions et Bibliographie Srvices services bibliographiques 395 Wellmgton Street 395, nie Weliingîm Ottawa ON KIA ON4 OrtawaON K1AON4 Canada Canada The author has granted a non- L'auteur a accordé une licence non exclusive Licence ailowing the exclusive permettant à la National Library of Canada to Bibliothèque nationale du Canada de reproduce, loan, distribute or sell reproduire, prêter, distribuer ou copies of this thesis in microform, vendre des copies de cette thèse sous paper or electronic formats. la forme de microfichelfilm, de reproduction sur papier ou sur format électronique. The author retains ownership of the L'auteur conserve la propriété du copyright in this thesis. Neither the droit d'auteur qui protège cette thèse. thesis nor substantial extracts fkom it Ni la thèse ni des extraits substantiels may be printed or othenvise de celle-ci ne doivent être imprimés reproduced without the author's ou autrement reproduits sans son permission. autorisation. TABLE OF CONTENTS Page Tableofcontents................................................... I Abstract .......................................................... VI Resumé........................................................... VI11 Acknowledgements ................................................. X Claim of contribution to kaowledge ................................... XI Listoffigures ...................................................... XllI Guidelines regarding doctoral thesis ................................... XV CHAPTER 1. INTRODUCTION .................................... 1 1. Overview: Life cycle of polyomavirus and simian virus 40 ..........