Predicting High-Impact Pharmacological Targets by Integrating Transcriptome and Text-Mining Features
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The International Journal of Biochemistry & Cell Biology
The International Journal of Biochemistry & Cell Biology 41 (2009) 1685–1696 Contents lists available at ScienceDirect The International Journal of Biochemistry & Cell Biology journal homepage: www.elsevier.com/locate/biocel Cathepsin X cleaves the C-terminal dipeptide of alpha- and gamma-enolase and impairs survival and neuritogenesis of neuronal cells Natasaˇ Obermajer a,b,∗, Bojan Doljak a, Polona Jamnik c,Ursaˇ Pecarˇ Fonovic´ a, Janko Kos a,b a University of Ljubljana, Faculty of Pharmacy, Askerceva 7, 1000 Ljubljana, Slovenia b Jozef Stefan Institute, Department of Biotechnology, Jamova 39, 1000 Ljubljana, Slovenia c University of Ljubljana, Biotechnical Faculty, Jamnikarjeva 101, 1000 Ljubljana, Slovenia article info abstract Article history: The cysteine carboxypeptidase cathepsin X has been recognized as an important player in degenerative Received 22 January 2009 processes during normal aging and in pathological conditions. In this study we identify isozymes alpha- Received in revised form 17 February 2009 and gamma-enolases as targets for cathepsin X. Cathepsin X sequentially cleaves C-terminal amino acids Accepted 18 February 2009 of both isozymes, abolishing their neurotrophic activity. Neuronal cell survival and neuritogenesis are, Available online 6 March 2009 in this way, regulated, as shown on pheochromocytoma cell line PC12. Inhibition of cathepsin X activity increases generation of plasmin, essential for neuronal differentiation and changes the length distribution Keywords: of neurites, especially in the early phase of neurite outgrowth. Moreover, cathepsin X inhibition increases Cathepsin X Enolase neuronal survival and reduces serum deprivation induced apoptosis, particularly in the absence of nerve Neuritogenesis growth factor. On the other hand, the proliferation of cells is decreased, indicating induction of differ- Neuronal cell survival entiation. -
Gentaur Products List
Chapter 2 : Gentaur Products List • Rabbit Anti LAMR1 Polyclonal Antibody Cy5 Conjugated Conjugated • Rabbit Anti Podoplanin gp36 Polyclonal Antibody Cy5 • Rabbit Anti LAMR1 CT Polyclonal Antibody Cy5 • Rabbit Anti phospho NFKB p65 Ser536 Polyclonal Conjugated Conjugated Antibody Cy5 Conjugated • Rabbit Anti CHRNA7 Polyclonal Antibody Cy5 Conjugated • Rat Anti IAA Monoclonal Antibody Cy5 Conjugated • Rabbit Anti EV71 VP1 CT Polyclonal Antibody Cy5 • Rabbit Anti Connexin 40 Polyclonal Antibody Cy5 • Rabbit Anti IAA Indole 3 Acetic Acid Polyclonal Antibody Conjugated Conjugated Cy5 Conjugated • Rabbit Anti LHR CGR Polyclonal Antibody Cy5 Conjugated • Rabbit Anti Integrin beta 7 Polyclonal Antibody Cy5 • Rabbit Anti Natrexone Polyclonal Antibody Cy5 Conjugated • Rabbit Anti MMP 20 Polyclonal Antibody Cy5 Conjugated Conjugated • Rabbit Anti Melamine Polyclonal Antibody Cy5 Conjugated • Rabbit Anti BCHE NT Polyclonal Antibody Cy5 Conjugated • Rabbit Anti NAP1 NAP1L1 Polyclonal Antibody Cy5 • Rabbit Anti Acetyl p53 K382 Polyclonal Antibody Cy5 • Rabbit Anti BCHE CT Polyclonal Antibody Cy5 Conjugated Conjugated Conjugated • Rabbit Anti HPV16 E6 Polyclonal Antibody Cy5 Conjugated • Rabbit Anti CCP Polyclonal Antibody Cy5 Conjugated • Rabbit Anti JAK2 Polyclonal Antibody Cy5 Conjugated • Rabbit Anti HPV18 E6 Polyclonal Antibody Cy5 Conjugated • Rabbit Anti HDC Polyclonal Antibody Cy5 Conjugated • Rabbit Anti Microsporidia protien Polyclonal Antibody Cy5 • Rabbit Anti HPV16 E7 Polyclonal Antibody Cy5 Conjugated • Rabbit Anti Neurocan Polyclonal -
Environmental Influences on Endothelial Gene Expression
ENDOTHELIAL CELL GENE EXPRESSION John Matthew Jeff Herbert Supervisors: Prof. Roy Bicknell and Dr. Victoria Heath PhD thesis University of Birmingham August 2012 University of Birmingham Research Archive e-theses repository This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder. ABSTRACT Tumour angiogenesis is a vital process in the pathology of tumour development and metastasis. Targeting markers of tumour endothelium provide a means of targeted destruction of a tumours oxygen and nutrient supply via destruction of tumour vasculature, which in turn ultimately leads to beneficial consequences to patients. Although current anti -angiogenic and vascular targeting strategies help patients, more potently in combination with chemo therapy, there is still a need for more tumour endothelial marker discoveries as current treatments have cardiovascular and other side effects. For the first time, the analyses of in-vivo biotinylation of an embryonic system is performed to obtain putative vascular targets. Also for the first time, deep sequencing is applied to freshly isolated tumour and normal endothelial cells from lung, colon and bladder tissues for the identification of pan-vascular-targets. Integration of the proteomic, deep sequencing, public cDNA libraries and microarrays, delivers 5,892 putative vascular targets to the science community. -
1 ICR-Geneset Gene List
ICR-geneset Gene List. IMAGE ID UniGene Locus Name Cluster 20115 Hs.62185 SLC9A6 solute carrier family 9 (sodium/hydrogen exchanger), isoform 6 21738 21899 Hs.78353 SRPK2 SFRS protein kinase 2 21908 Hs.79133 CDH8 cadherin 8, type 2 22040 Hs.151738 MMP9 matrix metalloproteinase 9 (gelatinase B, 92kD gelatinase, 92kD type IV collagenase) 22411 Hs.183 FY Duffy blood group 22731 Hs.1787 PHRET1 PH domain containing protein in retina 1 22859 Hs.356487 ESTs 22883 Hs.150926 FPGT fucose-1-phosphate guanylyltransferase 22918 Hs.346868 EBNA1BP2 EBNA1 binding protein 2 23012 Hs.158205 BLZF1 basic leucine zipper nuclear factor 1 (JEM-1) 23073 Hs.284244 FGF2 fibroblast growth factor 2 (basic) 23173 Hs.151051 MAPK10 mitogen-activated protein kinase 10 23185 Hs.289114 TNC tenascin C (hexabrachion) 23282 Hs.8024 IK IK cytokine, down-regulator of HLA II 23353 23431 Hs.50421 RB1CC1 RB1-inducible coiled-coil 1 23514 23548 Hs.71848 Human clone 23548 mRNA sequence 23629 Hs.135587 Human clone 23629 mRNA sequence 23658 Hs.265855 SETMAR SET domain and mariner transposase fusion gene 23676 Hs.100841 Homo sapiens clone 23676 mRNA sequence 23772 Hs.78788 LZTR1 leucine-zipper-like transcriptional regulator, 1 23776 Hs.75438 QDPR quinoid dihydropteridine reductase 23804 Hs.343586 ZFP36 zinc finger protein 36, C3H type, homolog (mouse) 23831 Hs.155247 ALDOC aldolase C, fructose-bisphosphate 23878 Hs.99902 OPCML opioid binding protein/cell adhesion molecule-like 23903 Hs.12526 Homo sapiens clone 23903 mRNA sequence 23932 Hs.368063 Human clone 23932 mRNA sequence 24004 -
Phylogenetic Analysis, Subcellular Localization, and Expression
BMC Plant Biology BioMed Central Research article Open Access Phylogenetic analysis, subcellular localization, and expression patterns of RPD3/HDA1 family histone deacetylases in plants Malona V Alinsug, Chun-Wei Yu and Keqiang Wu* Address: Institute of Plant Biology, College of Life Science, National Taiwan University, Taipei, Taiwan Email: Malona V Alinsug - [email protected]; Chun-Wei Yu - [email protected]; Keqiang Wu* - [email protected] * Corresponding author Published: 28 March 2009 Received: 26 November 2008 Accepted: 28 March 2009 BMC Plant Biology 2009, 9:37 doi:10.1186/1471-2229-9-37 This article is available from: http://www.biomedcentral.com/1471-2229/9/37 © 2009 Alinsug et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background: Although histone deacetylases from model organisms have been previously identified, there is no clear basis for the classification of histone deacetylases under the RPD3/ HDA1 superfamily, particularly on plants. Thus, this study aims to reconstruct a phylogenetic tree to determine evolutionary relationships between RPD3/HDA1 histone deacetylases from six different plants representing dicots with Arabidopsis thaliana, Populus trichocarpa, and Pinus taeda, monocots with Oryza sativa and Zea mays, and the lower plants with Physcomitrella patens. Results: Sixty two histone deacetylases of RPD3/HDA1 family from the six plant species were phylogenetically analyzed to determine corresponding orthologues. Three clusters were formed separating Class I, Class II, and Class IV. -
Serine Proteases with Altered Sensitivity to Activity-Modulating
(19) & (11) EP 2 045 321 A2 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: (51) Int Cl.: 08.04.2009 Bulletin 2009/15 C12N 9/00 (2006.01) C12N 15/00 (2006.01) C12Q 1/37 (2006.01) (21) Application number: 09150549.5 (22) Date of filing: 26.05.2006 (84) Designated Contracting States: • Haupts, Ulrich AT BE BG CH CY CZ DE DK EE ES FI FR GB GR 51519 Odenthal (DE) HU IE IS IT LI LT LU LV MC NL PL PT RO SE SI • Coco, Wayne SK TR 50737 Köln (DE) •Tebbe, Jan (30) Priority: 27.05.2005 EP 05104543 50733 Köln (DE) • Votsmeier, Christian (62) Document number(s) of the earlier application(s) in 50259 Pulheim (DE) accordance with Art. 76 EPC: • Scheidig, Andreas 06763303.2 / 1 883 696 50823 Köln (DE) (71) Applicant: Direvo Biotech AG (74) Representative: von Kreisler Selting Werner 50829 Köln (DE) Patentanwälte P.O. Box 10 22 41 (72) Inventors: 50462 Köln (DE) • Koltermann, André 82057 Icking (DE) Remarks: • Kettling, Ulrich This application was filed on 14-01-2009 as a 81477 München (DE) divisional application to the application mentioned under INID code 62. (54) Serine proteases with altered sensitivity to activity-modulating substances (57) The present invention provides variants of ser- screening of the library in the presence of one or several ine proteases of the S1 class with altered sensitivity to activity-modulating substances, selection of variants with one or more activity-modulating substances. A method altered sensitivity to one or several activity-modulating for the generation of such proteases is disclosed, com- substances and isolation of those polynucleotide se- prising the provision of a protease library encoding poly- quences that encode for the selected variants. -
The Use of Fluorescence Resonance Energy Transfer (FRET) Peptides for Measurement of Clinically Important Proteolytic Enzymes
“main” — 2009/7/27 — 13:55 — page 381 — #1 Anais da Academia Brasileira de Ciências (2009) 81(3): 381-392 (Annals of the Brazilian Academy of Sciences) ISSN 0001-3765 www.scielo.br/aabc The use of Fluorescence Resonance Energy Transfer (FRET) peptides for measurement of clinically important proteolytic enzymes ADRIANA K. CARMONA, MARIA APARECIDA JULIANO and LUIZ JULIANO Departamento de Biofísica, Escola Paulista de Medicina, Universidade Federal de São Paulo Rua 3 de Maio, 100, 04044-020 São Paulo, SP, Brasil Manuscript received on June 30, 2008; accepted for publication on September 9, 2008; contributed by LUIZ JULIANO* ABSTRACT Proteolytic enzymes have a fundamental role in many biological processes and are associated with multiple patholog- ical conditions. Therefore, targeting these enzymes may be important for a better understanding of their function and development of therapeutic inhibitors. Fluorescence Resonance Energy Transfer (FRET) peptides are convenient tools for the study of peptidases specificity as they allow monitoring of the reaction on a continuous basis, providing arapid method for the determination of enzymatic activity. Hydrolysis of a peptide bond between the donor/acceptor pair generates fluorescence that permits the measurement of the activity of nanomolar concentrations of the enzyme.The assays can be performed directly in a cuvette of the fluorimeter or adapted for determinations in a 96-well fluorescence plate reader. The synthesis of FRET peptides containing ortho-aminobenzoic acid (Abz) as fluorescent group and 2,4-dinitrophenyl (Dnp) or N-(2,4-dinitrophenyl)ethylenediamine (EDDnp) as quencher was optimized by our group and became an important line of research at the Department of Biophysics of the Federal University of São Paulo. -
Angiopoietin/Tek Interactions Regulate MMP-9 Expression and Retinal Neovascularization
0023-6837/03/8311-1637$03.00/0 LABORATORY INVESTIGATION Vol. 83, No. 11, p. 1637, 2003 Copyright © 2003 by The United States and Canadian Academy of Pathology, Inc. Printed in U.S.A. Angiopoietin/Tek Interactions Regulate MMP-9 Expression and Retinal Neovascularization Arup Das, William Fanslow, Douglas Cerretti, Erin Warren, Nicholas Talarico, and Paul McGuire Department of Surgery (AD, PM), Division of Ophthalmology, Cell Biology and Physiology (AD, EW, NT, PM), University of New Mexico School of Medicine, and New Mexico Veterans Health Care System (AD), Albuquerque, New Mexico; and Cancer Pharmacology Amgen Washington (WF, DC), Seattle, Washington SUMMARY: The objective of the study was to determine the role of the angiopoietins in the regulation of gelatinase expression during angiogenesis, and whether inhibition of the angiopoietin/Tek interaction in vivo can suppress the extent of retinal neovascularization. Retinal microvascular endothelial cells were treated with angiopoietins and examined for the production of gelatinases. The effects of inhibiting angiopoietin binding to the Tie-2 receptor was studied in newborn mice with experimentally induced retinal neovascularization. Animals were treated with an ip injection of the Tie-2 antagonist, muTek delta Fc, while oxygen-exposed mice treated with similar concentrations of murine IgG were used as controls. The effect of muTek delta Fc on the gelatinase expression in the retina was examined by real-time RT-PCR analysis. The stimulation of cultured retinal endothelial cells with Ang-1 and -2 resulted in the increased expression of matrix metalloproteinase (MMP)-9. Ang-2 expression was up-regulated in experimental animals during the period of angiogenesis and was the greatest on Day 17 (the time of maximal angiogenic response). -
Appendix Table A.2.3.1 Full Table of All Chicken Proteins and Human Orthologs Pool Accession Human Human Protein Human Product Cell Angios Log2( Endo Gene Comp
Appendix table A.2.3.1 Full table of all chicken proteins and human orthologs Pool Accession Human Human Protein Human Product Cell AngioS log2( Endo Gene comp. core FC) Specific CIKL F1NWM6 KDR NP_002244 kinase insert domain receptor (a type III receptor tyrosine M 94 4 kinase) CWT Q8AYD0 CDH5 NP_001786 cadherin 5, type 2 (vascular endothelium) M 90 8.45 specific CWT Q8AYD0 CDH5 NP_001786 cadherin 5, type 2 (vascular endothelium) M 90 8.45 specific CIKL F1P1Y9 CDH5 NP_001786 cadherin 5, type 2 (vascular endothelium) M 90 8.45 specific CIKL F1P1Y9 CDH5 NP_001786 cadherin 5, type 2 (vascular endothelium) M 90 8.45 specific CIKL F1N871 FLT4 NP_891555 fms-related tyrosine kinase 4 M 86 -1.71 CWT O73739 EDNRA NP_001948 endothelin receptor type A M 81 -8 CIKL O73739 EDNRA NP_001948 endothelin receptor type A M 81 -8 CWT Q4ADW2 PROCR NP_006395 protein C receptor, endothelial M 80 -0.36 CIKL Q4ADW2 PROCR NP_006395 protein C receptor, endothelial M 80 -0.36 CIKL F1NFQ9 TEK NP_000450 TEK tyrosine kinase, endothelial M 77 7.3 specific CWT Q9DGN6 ECE1 NP_001106819 endothelin converting enzyme 1 M 74 -0.31 CIKL Q9DGN6 ECE1 NP_001106819 endothelin converting enzyme 1 M 74 -0.31 CWT F1NIF0 CA9 NP_001207 carbonic anhydrase IX I 74 CIKL F1NIF0 CA9 NP_001207 carbonic anhydrase IX I 74 CWT E1BZU7 AOC3 NP_003725 amine oxidase, copper containing 3 (vascular adhesion protein M 70 1) CIKL E1BZU7 AOC3 NP_003725 amine oxidase, copper containing 3 (vascular adhesion protein M 70 1) CWT O93419 COL18A1 NP_569712 collagen, type XVIII, alpha 1 E 70 -2.13 CIKL O93419 -
Crystal Structure of Cathepsin X: a Flip–Flop of the Ring of His23
st8308.qxd 03/22/2000 11:36 Page 305 Research Article 305 Crystal structure of cathepsin X: a flip–flop of the ring of His23 allows carboxy-monopeptidase and carboxy-dipeptidase activity of the protease Gregor Guncar1, Ivica Klemencic1, Boris Turk1, Vito Turk1, Adriana Karaoglanovic-Carmona2, Luiz Juliano2 and Dušan Turk1* Background: Cathepsin X is a widespread, abundantly expressed papain-like Addresses: 1Department of Biochemistry and v mammalian lysosomal cysteine protease. It exhibits carboxy-monopeptidase as Molecular Biology, Jozef Stefan Institute, Jamova 39, 1000 Ljubljana, Slovenia and 2Departamento de well as carboxy-dipeptidase activity and shares a similar activity profile with Biofisica, Escola Paulista de Medicina, Rua Tres de cathepsin B. The latter has been implicated in normal physiological events as Maio 100, 04044-020 Sao Paulo, Brazil. well as in various pathological states such as rheumatoid arthritis, Alzheimer’s disease and cancer progression. Thus the question is raised as to which of the *Corresponding author. E-mail: [email protected] two enzyme activities has actually been monitored. Key words: Alzheimer’s disease, carboxypeptidase, Results: The crystal structure of human cathepsin X has been determined at cathepsin B, cathepsin X, papain-like cysteine 2.67 Å resolution. The structure shares the common features of a papain-like protease enzyme fold, but with a unique active site. The most pronounced feature of the Received: 1 November 1999 cathepsin X structure is the mini-loop that includes a short three-residue Revisions requested: 8 December 1999 insertion protruding into the active site of the protease. The residue Tyr27 on Revisions received: 6 January 2000 one side of the loop forms the surface of the S1 substrate-binding site, and Accepted: 7 January 2000 His23 on the other side modulates both carboxy-monopeptidase as well as Published: 29 February 2000 carboxy-dipeptidase activity of the enzyme by binding the C-terminal carboxyl group of a substrate in two different sidechain conformations. -
HCC and Cancer Mutated Genes Summarized in the Literature Gene Symbol Gene Name References*
HCC and cancer mutated genes summarized in the literature Gene symbol Gene name References* A2M Alpha-2-macroglobulin (4) ABL1 c-abl oncogene 1, receptor tyrosine kinase (4,5,22) ACBD7 Acyl-Coenzyme A binding domain containing 7 (23) ACTL6A Actin-like 6A (4,5) ACTL6B Actin-like 6B (4) ACVR1B Activin A receptor, type IB (21,22) ACVR2A Activin A receptor, type IIA (4,21) ADAM10 ADAM metallopeptidase domain 10 (5) ADAMTS9 ADAM metallopeptidase with thrombospondin type 1 motif, 9 (4) ADCY2 Adenylate cyclase 2 (brain) (26) AJUBA Ajuba LIM protein (21) AKAP9 A kinase (PRKA) anchor protein (yotiao) 9 (4) Akt AKT serine/threonine kinase (28) AKT1 v-akt murine thymoma viral oncogene homolog 1 (5,21,22) AKT2 v-akt murine thymoma viral oncogene homolog 2 (4) ALB Albumin (4) ALK Anaplastic lymphoma receptor tyrosine kinase (22) AMPH Amphiphysin (24) ANK3 Ankyrin 3, node of Ranvier (ankyrin G) (4) ANKRD12 Ankyrin repeat domain 12 (4) ANO1 Anoctamin 1, calcium activated chloride channel (4) APC Adenomatous polyposis coli (4,5,21,22,25,28) APOB Apolipoprotein B [including Ag(x) antigen] (4) AR Androgen receptor (5,21-23) ARAP1 ArfGAP with RhoGAP domain, ankyrin repeat and PH domain 1 (4) ARHGAP35 Rho GTPase activating protein 35 (21) ARID1A AT rich interactive domain 1A (SWI-like) (4,5,21,22,24,25,27,28) ARID1B AT rich interactive domain 1B (SWI1-like) (4,5,22) ARID2 AT rich interactive domain 2 (ARID, RFX-like) (4,5,22,24,25,27,28) ARID4A AT rich interactive domain 4A (RBP1-like) (28) ARID5B AT rich interactive domain 5B (MRF1-like) (21) ASPM Asp (abnormal -
Steroid Sulfatase of Human Leukocytes and Epidermis and the Diagnosis of Recessive X-Linked Ichthyosis
Steroid sulfatase of human leukocytes and epidermis and the diagnosis of recessive X-linked ichthyosis. E H Epstein Jr, M E Leventhal J Clin Invest. 1981;67(5):1257-1262. https://doi.org/10.1172/JCI110153. Research Article Patients with recessive X-linked ichthyosis, one of the inherited types of excessive stratum corneum cohesion, have deficient steroid sulfatase in fibroblasts grown from their dermis. Because of the expense and long period required to grow such cells, we have assayed this enzyme in peripheral blood leukocytes and found it to be undetectable in those from patients with this type of ichthyosis, but normal in those from patients with other hereditary or acquired types of ichthyosis. In addition, steroid sulfatase activity is less in leukocytes from women who are carriers of this disease than normal women, and this assay can be used to detect such carriers. Despite previous studies demonstrating that the gene for this enzyme escapes the inactivation of other x-chromosome genes, normal women have leukocyte steroid sulfatase activity only 1.3 times that of normal men, suggesting that some gene dosage compensation occurs. Normal human epidermis, the tissue most affected clinically, also expresses steroid sulfatase activity. The epidermal enzyme is similar in its subcellular localization, its molecular size, and kinetically to that of placenta, leukocytes, and fibroblasts. Find the latest version: https://jci.me/110153/pdf Steroid Sulfatase of Human Leukocytes and Epidermis and the Diagnosis of Recessive X-linked Ichthyosis ERVIN H. EPSTEIN, JR., and MARY E. LEVENTHAL, Dermatology Unit of the Medical Service, San Francisco General Hospital Medical Center, Department of Dermatology, University of California, San Francisco, California 94110 A B S T R A C T Patients with recessive X-linked pearance especially on the side of the neck, and the ichthyosis, one of the inherited types of excessive subsequently described comeal stippling (2).