DOCSLIB.ORG

Mass Destruction Prediction Power

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Mass Destruction Prediction Power HIGHLIGHTS PROGNOSIS Wouldn’t we all like the power to pre- good-prognosis groups. The progno- dict the future? For breast cancer sis signature assigned 115 tumours to patients, the accuracy with which the the good-prognosis category and 180 progress of their disease can be to the poor-prognosis category. There Prediction power mapped can make the difference was a strong correlation between the between whether they are overtreated probability of remaining free of or undertreated and can also affect metastases and of surviving, and the predictions of their survival. Current good-prognosis signature. criteria used for prognosis in breast Interestingly, the prognostic profile cancer include age, the size of the was independent of lymph-node sta- tumour, axillary-node status, histo- tus, but was also highly predictive of logical type, pathological grade and the risk of distant metastases in the hormone-receptor status. van de lymph-node-positive subgroup. This Vijver and colleagues now add a could be useful for identifying patients gene-expression profile to the list of with lymph-node-positive disease useful prognostic indicators, as they who have an unexpectedly good prog- report in the 19 December issue of nosis and indicates that lymph-node New England Journal of Medicine. metastases develop independently of The authors used a 70-gene prog- distant metastases. nosis profile that was first described The gene-expression profile was by the same research team earlier in also predictive of overall survival — 2002 to classify 295 patients with pri- 94.5% of patients in the good-prog- mary breast cancer — which nosis group survived for 10 years included 61 of the 78 patients, all compared with 54.6% in the poor- lymph-node negative, from the first prognosis group. The hazard ratio study — into poor-prognosis and for distant metastases in the poor- THERAPEUTICS Mass destruction The urokinase pathway is involved in So, how toxic are these toxins? When just the size of the tumours by more than 85%, physiological and pathological tissue 2 µg of the native anthrax toxin, PrAg, was and completely eradicated all remodelling processes, including cancer given to mice with FB59, extreme toxicity was fibrosarcomas in 67% of mice after only invasion and metastasis. Both urokinase observed — widespread organ damage and one treatment. No increase in apoptosis plasminogen activator (uPA) and its death occurred within a few hours. By was seen, indicating that the toxin triggered receptor (uPAR) are overexpressed in contrast, up to 30 µg of the modified toxin, necrotic cell death. nearly all human cancers, but are only PrAg-U2, resulted in no toxicity. Next, the The engineered toxin suppressed tumour expressed at very low levels in normal authors used mice with complete deficiencies growth and destroyed established tumours tissues, except as a rapid response to tissue in key components of the urokinase pathway with no toxicity to normal tissues. Because injury. Bugge, Leppla and colleagues have — including plasminogen (Plg), which is uPA is overexpressed on epithelial, exploited this tumour-associated uPA activated by urokinase — to show that the mesenchymal and haematopoietic tumours, system to activate a targeted immunotoxin, uPA system is crucial in activation of PrAg- this strategy has promise as a broad-acting based on anthrax, which causes potent U2. Whereas wild-type mice died when given antitumour therapy. The authors suggest destruction of tumours. 40−200 µg PrAg-U2 plus FP59, uPA–/–, that modifications could be made to Anthrax toxin is secreted by bacteria as uPAR–/– and Plg–/– mice remained healthy, increase protease specificity or to use other three antigens and is activated when the and mice null for uPA inhibitor were toxin proteins instead of anthrax. The protective antigen (PrAg) binds to a hypersensitive to the toxin. This shows that therapeutic index of immunotoxins already ubiquitously expressed cell-surface receptor the components of the uPA pathway are in clinical use might also be improved by (tumour endothelium marker 8), is cleaved crucial to the activation of PrAg-U2 in vivo. adapting this strategy. by furin proteases and forms a complex The authors now knew that PrAg-U2 was Ezzie Hutchinson with the two other antigens. Binding of the specifically activated by the tumour- active part of the complex with fusion associated urokinase system, so they next References and links ORIGINAL RESEARCH PAPER Liu, S. et al. Potent protein 59 (FP59) kills the cell by inhibiting tested the tumoricidal activity of the toxin antitumour activity of a urokinase-activated engineered translation elongation factor 2. The authors in mice bearing established fibrosarcomas, anthrax toxin. Proc. Natl Acad. Sci. 13 Jan 2003 modified PrAg so that it is cleaved by uPA melano-mas and lung carcinomas — (doi:10.1073/pnas.0236849100) WEB SITE and not by furin, so that only cancer cells tumours that have a poor response to Thomas Bugge’s lab: would be targeted. conventional treatment. PrAg-U2 reduced http://wwwdir.nidcr.nih.gov/dirweb/opcb/ptru.asp 82 | FEBRUARY 2003 | VOLUME 3 www.nature.com/reviews/cancer © 2003 Nature Publishing Group.
Load more

Recommended publications
  • A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
    Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated.
    [Show full text]
  • TMPRSS2 and Furin Are Both Essential for Proteolytic Activation of SARS-Cov-2 in Human Airway Cells
    Research Article TMPRSS2 and furin are both essential for proteolytic activation of SARS-CoV-2 in human airway cells Dorothea Bestle1,*, Miriam Ruth Heindl1,*, Hannah Limburg1,*, Thuy Van Lam van2 , Oliver Pilgram2, Hong Moulton3, David A Stein3 , Kornelia Hardes2,4, Markus Eickmann1,5, Olga Dolnik1,5 , Cornelius Rohde1,5, Hans-Dieter Klenk1, Wolfgang Garten1, Torsten Steinmetzer2, Eva Bottcher-Friebertsh¨ auser¨ 1 The novel emerged SARS-CoV-2 has rapidly spread around the broad range of mammalian and avian species, causing respiratory world causing acute infection of the respiratory tract (COVID-19) or enteric diseases. CoVs have a major surface protein, the spike (S) that can result in severe disease and lethality. For SARS-CoV-2 to protein, which initiates infection by receptor binding and fusion of enter cells, its surface glycoprotein spike (S) must be cleaved at the viral lipid envelope with cellular membranes. Like fusion two different sites by host cell proteases, which therefore rep- proteins of many other viruses, the S protein is activated by cellular resent potential drug targets. In the present study, we show that S proteases. Activation of CoV S is a complex process that requires can be cleaved by the proprotein convertase furin at the S1/S2 proteolytic cleavage of S at two distinct sites, S1/S2 and S29 (Fig 1), site and the transmembrane serine protease 2 (TMPRSS2) at the generating the subunits S1 and S2 that remain non-covalently S29 site. We demonstrate that TMPRSS2 is essential for activation linked (1, 2, 3). The S1 subunit contains the receptor binding do- of SARS-CoV-2 S in Calu-3 human airway epithelial cells through main, whereas the S2 subunit is membrane-anchored and harbors antisense-mediated knockdown of TMPRSS2 expression.
    [Show full text]
  • Coagulation Factors Directly Cleave SARS-Cov-2 Spike and Enhance Viral Entry
    bioRxiv preprint doi: https://doi.org/10.1101/2021.03.31.437960; this version posted April 1, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Coagulation factors directly cleave SARS-CoV-2 spike and enhance viral entry. Edward R. Kastenhuber1, Javier A. Jaimes2, Jared L. Johnson1, Marisa Mercadante1, Frauke Muecksch3, Yiska Weisblum3, Yaron Bram4, Robert E. Schwartz4,5, Gary R. Whittaker2 and Lewis C. Cantley1,* Affiliations 1. Meyer Cancer Center, Department of Medicine, Weill Cornell Medical College, New York, NY, USA. 2. Department of Microbiology and Immunology, Cornell University, Ithaca, New York, USA. 3. Laboratory of Retrovirology, The Rockefeller University, New York, NY, USA. 4. Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medicine, New York, NY, USA. 5. Department of Physiology, Biophysics and Systems Biology, Weill Cornell Medicine, New York, NY, USA. *Correspondence: [email protected] bioRxiv preprint doi: https://doi.org/10.1101/2021.03.31.437960; this version posted April 1, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Summary Coagulopathy is recognized as a significant aspect of morbidity in COVID-19 patients. The clotting cascade is propagated by a series of proteases, including factor Xa and thrombin. Other host proteases, including TMPRSS2, are recognized to be important for cleavage activation of SARS-CoV-2 spike to promote viral entry. Using biochemical and cell-based assays, we demonstrate that factor Xa and thrombin can also directly cleave SARS-CoV-2 spike, enhancing viral entry.
    [Show full text]
  • Demonstration of Proteolytic Activation of the Epithelial Sodium Channel (Enac) by Combining Current Measurements with Detection of Cleavage Fragments
    Journal of Visualized Experiments www.jove.com Video Article Demonstration of Proteolytic Activation of the Epithelial Sodium Channel (ENaC) by Combining Current Measurements with Detection of Cleavage Fragments Matteus Krappitz1, Christoph Korbmacher1, Silke Haerteis1 1 Institut für Zelluläre und Molekulare Physiologie, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) Correspondence to: Silke Haerteis at [email protected] URL: http://www.jove.com/video/51582 DOI: doi:10.3791/51582 Keywords: Biochemistry, Issue 89, two-electrode voltage-clamp, electrophysiology, biotinylation, Xenopus laevis oocytes, epithelial sodium channel, ENaC, proteases, proteolytic channel activation, ion channel, cleavage sites, cleavage fragments Date Published: 7/5/2014 Citation: Krappitz, M., Korbmacher, C., Haerteis, S. Demonstration of Proteolytic Activation of the Epithelial Sodium Channel (ENaC) by Combining Current Measurements with Detection of Cleavage Fragments. J. Vis. Exp. (89), e51582, doi:10.3791/51582 (2014). Abstract The described methods can be used to investigate the effect of proteases on ion channels, receptors, and other plasma membrane proteins heterologously expressed in Xenopus laevis oocytes. In combination with site-directed mutagenesis, this approach provides a powerful tool to identify functionally relevant cleavage sites. Proteolytic activation is a characteristic feature of the amiloride-sensitive epithelial sodium channel (ENaC). The final activating step involves cleavage of the channel’s γ-subunit in a critical region potentially targeted by several proteases including chymotrypsin and plasmin. To determine the stimulatory effect of these serine proteases on ENaC, the amiloride-sensitive whole- cell current (ΔIami) was measured twice in the same oocyte before and after exposure to the protease using the two-electrode voltage-clamp technique.
    [Show full text]
  • Fibrinolysis Influences SARS-Cov-2 Infection in Ciliated Cells
    bioRxiv preprint doi: https://doi.org/10.1101/2021.01.07.425801; this version posted January 8, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 1 Fibrinolysis influences SARS-CoV-2 infection in ciliated cells 2 3 Yapeng Hou1, Yan Ding1, Hongguang Nie1, *, Hong-Long Ji2 4 5 1Department of Stem Cells and Regenerative Medicine, College of Basic Medical Science, China Medical 6 University, Shenyang, Liaoning 110122, China. 2Department of Cellular and Molecular Biology, University 7 of Texas Health Science Center at Tyler, Tyler, TX 75708, USA. 8 9 *Address correspondence to [email protected] 10 11 bioRxiv preprint doi: https://doi.org/10.1101/2021.01.07.425801; this version posted January 8, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 12 Abstract 13 Rapid spread of COVID-19 has caused an unprecedented pandemic worldwide, and an inserted furin site 14 in SARS-CoV-2 spike protein (S) may account for increased transmissibility. Plasmin, and other host 15 proteases, may cleave the furin site of SARS-CoV-2 S protein and subunits of epithelial sodium channels ( 16 ENaC), resulting in an increment in virus infectivity and channel activity. As for the importance of ENaC in 17 the regulation of airway surface and alveolar fluid homeostasis, whether SARS-CoV-2 will share and 18 strengthen the cleavage network with ENaC proteins at the single-cell level is urgently worthy of consideration.
    [Show full text]
  • Importance of Reelin C-Terminal Region in the Development and Maintenance of the Postnatal Cerebral Cortex and Its Regulation by Specific Proteolysis
    4776 • The Journal of Neuroscience, March 18, 2015 • 35(11):4776–4787 Cellular/Molecular Importance of Reelin C-Terminal Region in the Development and Maintenance of the Postnatal Cerebral Cortex and Its Regulation by Specific Proteolysis Takao Kohno,1* Takao Honda,2* Ken-ichiro Kubo,2* Yoshimi Nakano,1 Ayaka Tsuchiya,1 Tatsuro Murakami,1 Hideyuki Banno,1 Kazunori Nakajima,2† and Mitsuharu Hattori1† 1Department of Biomedical Science, Graduate School of Pharmaceutical Sciences, Nagoya City University, Aichi 467-8603, Japan, and 2Department of Anatomy, Keio University School of Medicine, Tokyo 160-8582, Japan During brain development, Reelin exerts a variety of effects in a context-dependent manner, whereas its underlying molecular mecha- nisms remain poorly understood. We previously showed that the C-terminal region (CTR) of Reelin is required for efficient induction of phosphorylation of Dab1, an essential adaptor protein for canonical Reelin signaling. However, the physiological significance of the Reelin CTR in vivo remains unexplored. To dissect out Reelin functions, we made a knock-in (KI) mouse in which the Reelin CTR is deleted. The amount of Dab1, an indication of canonical Reelin signaling strength, is increased in the KI mouse, indicating that the CTR is necessary for efficient induction of Dab1 phosphorylation in vivo. Formation of layer structures during embryonic development is normal in the KI mouse. Intriguingly, the marginal zone (MZ) of the cerebral cortex becomes narrower at postnatal stages because upper-layer neurons invade the MZ and their apical dendrites are misoriented and poorly branched. Furthermore, Reelin undergoes proteolytic cleavage by proprotein convertases at a site located 6 residues from the C terminus, and it was suggested that this cleavage abrogates the Reelin binding to the neuronal cell membrane.
    [Show full text]
  • TMPRSS2 and Furin Are Both Essential for Proteolytic Activation and Spread of SARS-Cov-2 in Human Airway Epithelial Cells and Pr
    bioRxiv preprint doi: https://doi.org/10.1101/2020.04.15.042085; this version posted April 15, 2020. 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 TMPRSS2 and furin are both essential for proteolytic activation and spread of SARS- 2 CoV-2 in human airway epithelial cells and provide promising drug targets 3 4 5 Dorothea Bestle1#, Miriam Ruth Heindl1#, Hannah Limburg1#, Thuy Van Lam van2, Oliver 6 Pilgram2, Hong Moulton3, David A. Stein3, Kornelia Hardes2,4, Markus Eickmann1,5, Olga 7 Dolnik1,5, Cornelius Rohde1,5, Stephan Becker1,5, Hans-Dieter Klenk1, Wolfgang Garten1, 8 Torsten Steinmetzer2, and Eva Böttcher-Friebertshäuser1* 9 10 1) Institute of Virology, Philipps-University, Marburg, Germany 11 2) Institute of Pharmaceutical Chemistry, Philipps-University, Marburg, Germany 12 3) Department of Biomedical Sciences, Carlson College of Veterinary Medicine, Oregon 13 State University, Corvallis, USA 14 4) Fraunhofer Institute for Molecular Biology and Applied Ecology, Gießen, Germany 15 5) German Center for Infection Research (DZIF), Marburg-Gießen-Langen Site, Emerging 16 Infections Unit, Philipps-University, Marburg, Germany 17 18 #These authors contributed equally to this work. 19 20 *Corresponding author: Eva Böttcher-Friebertshäuser 21 Institute of Virology, Philipps-University Marburg 22 Hans-Meerwein-Straße 2, 35043 Marburg, Germany 23 Tel: 0049-6421-2866019 24 E-mail: [email protected] 25 26 Short title: TMPRSS2 and furin activate SARS-CoV-2 spike protein 27 28 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.04.15.042085; this version posted April 15, 2020.
    [Show full text]
  • Engineered Type 1 Regulatory T Cells Designed for Clinical Use Kill Primary
    ARTICLE Acute Myeloid Leukemia Engineered type 1 regulatory T cells designed Ferrata Storti Foundation for clinical use kill primary pediatric acute myeloid leukemia cells Brandon Cieniewicz,1* Molly Javier Uyeda,1,2* Ping (Pauline) Chen,1 Ece Canan Sayitoglu,1 Jeffrey Mao-Hwa Liu,1 Grazia Andolfi,3 Katharine Greenthal,1 Alice Bertaina,1,4 Silvia Gregori,3 Rosa Bacchetta,1,4 Norman James Lacayo,1 Alma-Martina Cepika1,4# and Maria Grazia Roncarolo1,2,4# Haematologica 2021 Volume 106(10):2588-2597 1Department of Pediatrics, Division of Stem Cell Transplantation and Regenerative Medicine, Stanford School of Medicine, Stanford, CA, USA; 2Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford School of Medicine, Stanford, CA, USA; 3San Raffaele Telethon Institute for Gene Therapy, Milan, Italy and 4Center for Definitive and Curative Medicine, Stanford School of Medicine, Stanford, CA, USA *BC and MJU contributed equally as co-first authors #AMC and MGR contributed equally as co-senior authors ABSTRACT ype 1 regulatory (Tr1) T cells induced by enforced expression of interleukin-10 (LV-10) are being developed as a novel treatment for Tchemotherapy-resistant myeloid leukemias. In vivo, LV-10 cells do not cause graft-versus-host disease while mediating graft-versus-leukemia effect against adult acute myeloid leukemia (AML). Since pediatric AML (pAML) and adult AML are different on a genetic and epigenetic level, we investigate herein whether LV-10 cells also efficiently kill pAML cells. We show that the majority of primary pAML are killed by LV-10 cells, with different levels of sensitivity to killing. Transcriptionally, pAML sensitive to LV-10 killing expressed a myeloid maturation signature.
    [Show full text]
  • (Tpa) Signal Sequence Enhances Immunogenicity of MVA-Based
    Immunology Letters 190 (2017) 51–57 Contents lists available at ScienceDirect Immunology Letters journal homepage: www.elsevier.com/locate/immlet Tissue plasminogen activator (tPA) signal sequence enhances MARK immunogenicity of MVA-based vaccine against tuberculosis Yiming Koua, Yongqing Xua, Zhilei Zhaoa, Jie Liua, Yang Wua, Qingrui Youa, Linli Wanga, ⁎ ⁎ Feng Gaoa,b, Linjun Caia,b, , Chunlai Jianga,b, a National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University, Changchun 130012, PR China b Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, School of Life Science, Jilin University, Changchun 130012, PR China ARTICLE INFO ABSTRACT Keywords: Tuberculosis (TB) remains a serious health problem worldwide, and the only available vaccine, bacillus Tuberculosis Calmette-Guérin (BCG), has shown highly variable efficacy in adults against TB. New vaccines are urgently Tissue plasminogen activator signal sequence needed, and the modified vaccinia virus Ankara (MVA)-based vaccine has emerged as one of the most promising fi Modi ed vaccinia virus Ankara candidates based on many preclinical and early clinical studies over the past few years. However, the maximum Ag85B tolerable dose and strength of induced immune responses have limited the protective effect of MVA-based TB10.4 prophylactic vaccines. To improve the immunogenicity of MVA-based vaccines, we introduced the tPA signal sequence in order to increase the antigen expression and secretion. Two recombinant MVA vectors expressing the Ag85B-TB10.4 fusion protein with or without tPA signal sequence were constructed and verified. Following the homologous prime-boost administration regimen in mice, levels of antigen-specific antibodies and cytokines (e.g., IFN-γ, TNF-α, IL-5, IL-6) and the percent of activated T cells were found to be significantly increased by the tPA signal sequence.
    [Show full text]
  • And VLDL Receptor
    International Journal of Molecular Sciences Review The Reelin Receptors Apolipoprotein E receptor 2 (ApoER2) and VLDL Receptor Paula Dlugosz and Johannes Nimpf * Department of Medical Biochemistry, Max F. Perutz Laboratories, Medical University Vienna, 1030 Vienna, Austria; [email protected] * Correspondence: [email protected], Tel.: +43-1-4277-61808, Fax: +43-1-4277-9618 Received: 28 August 2018; Accepted: 3 October 2018; Published: 9 October 2018 Abstract: Apolipoprotein E receptor 2 (ApoER2) and VLDL receptor belong to the low density lipoprotein receptor family and bind apolipoprotein E. These receptors interact with the clathrin machinery to mediate endocytosis of macromolecules but also interact with other adapter proteins to perform as signal transduction receptors. The best characterized signaling pathway in which ApoER2 and VLDL receptor (VLDLR) are involved is the Reelin pathway. This pathway plays a pivotal role in the development of laminated structures of the brain and in synaptic plasticity of the adult brain. Since Reelin and apolipoprotein E, are ligands of ApoER2 and VLDLR, these receptors are of interest with respect to Alzheimer’s disease. We will focus this review on the complex structure of ApoER2 and VLDLR and a recently characterized ligand, namely clusterin. Keywords: apolipoprotein E receptor 2; VLDL receptor; reelin; clusterin; Alzheimer’s disease 1. Introduction Apolipoprotein E receptor 2 (ApoER2) and VLDL receptor (VLDLR) belong to the low density lipoprotein receptor (LDLR) family, a class of type-I transmembrane receptors with high homology to their name-giving member the LDL receptor. Besides more distant members of this family, such as LRP 1, 1b, 2, 5, and 6; ApoER2, VLDLR, and LDLR have a superimposable structure indicating that the corresponding genes may have evolved from one single ancestor by gene duplication events and minor exon rearrangements.
    [Show full text]
  • ACE2 and FURIN Supplemental Figure S1
    ACE2 and FURIN Supplemental Figure S1. Expression in human cells, tissues, and organs RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors) RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors) RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors) RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors) Jensen TISSUES ARCHS4 Human Tissues ACE2 and FURIN Supplemental Figure S2. Effects of viral challenges on expression Virus Perturbations from GEO up Profile: FURIN expression in peripheral blood mononuclear cells (PBMCs) GDS1028 / 201945_at Title Severe acute respiratory syndrome expression profile Organism Homo sapiens FURIN expression in peripheral blood mononuclear cells (PBMCs) p = 0.002 Sample Title Value GSM30361 N1 264.2 GSM30362 N2 241.7 GSM30363 N3 298.1 GSM30364 N4 268.5 GSM30365 S1 295.5 GSM30366 S2 464 GSM30367 S3 309.7 GSM30368 S4 564.1 GSM30369 S5 674.4 GSM30370 S6 588 GSM30371 S7 830.2 GSM30372 S8 818.8 GSM30373 S9 385.1 GSM30374 S10 771.2 ACE2 and FURIN Supplemental Figure S3. Effects of common human diseases on expression changes Distinct patterns of diseases associated with increased expression of the ACE2 and FURIN genes Disease Perturbations from GEO up Distinct patterns of diseases associated with expression changes of the ACE2 and FURIN genes DisGeNET Profile: ACE2 expression GDS4855 / 222257_s_at Title Pandemic and seasonal H1N1 influenza virus infections of bronchial epithelial cells in vitro Organism Homo sapiens Effects of pandemic and seasonal H1N1 influenza virus infections on ACE2 expression
    [Show full text]
  • Myeloid Cell Expressed Proprotein Convertase FURIN Attenuates Inflammation
    www.impactjournals.com/oncotarget/ Oncotarget, Vol. 7, No. 34 Research Paper: Immunology Myeloid cell expressed proprotein convertase FURIN attenuates inflammation Zuzet Martinez Cordova1, Anna Grönholm1, Ville Kytölä2, Valentina Taverniti3, Sanna Hämäläinen1, Saara Aittomäki1, Wilhelmiina Niininen1, Ilkka Junttila4,5, Antti Ylipää2, Matti Nykter2 and Marko Pesu1,6 1 Team Immunoregulation, Institute of Biosciences and Medical Technology (BioMediTech), University of Tampere, Tampere, Finland 2 Team Computational Biology, Institute of Biosciences and Medical Technology (BioMediTech), University of Tampere, Tampere, Finland 3 Department of Food, Environmental and Nutritional Sciences (DeFENS), Division of Food Microbiology and Bioprocessing, Università degli Studi di Milano, Milan, Italy 4 School of Medicine, University of Tampere, Tampere, Finland 5 Fimlab Laboratories, Pirkanmaa Hospital District, Tampere, Finland 6 Department of Dermatology, Tampere University Hospital, Tampere, Finland Correspondence to: Marko Pesu, email: [email protected] Keywords: cytokine, FURIN, LysM, macrophage, TGF-β1, Immunology and Microbiology Section, Immune response, Immunity Received: February 25, 2016 Accepted: July 22, 2016 Published: August 05, 2016 ABSTRACT The proprotein convertase enzyme FURIN processes immature pro-proteins into functional end- products. FURIN is upregulated in activated immune cells and it regulates T-cell dependent peripheral tolerance and the Th1/Th2 balance. FURIN also promotes the infectivity of pathogens by activating bacterial toxins and by processing viral proteins. Here, we evaluated the role of FURIN in LysM+ myeloid cells in vivo. Mice with a conditional deletion of FURIN in their myeloid cells (LysMCre-fur(fl/fl)) were healthy and showed unchanged proportions of neutrophils and macrophages. Instead, LysMCre-fur(fl/fl) mice had elevated serum IL-1β levels and reduced numbers of splenocytes.
    [Show full text]