Supplementary Table 4: the Association of the 26S Proteasome
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The Potential Role of Necroptosis in Clinical Diseases (Review)
INTERNATIONAL JOURNAL OF MOleCular meDICine 47: 89, 2021 The potential role of necroptosis in clinical diseases (Review) WENLI DAI1*, JIN CHENG1*, XI LENG2, XIAOQING HU1 and YINGFANG AO1 1Institute of Sports Medicine, Beijing Key Laboratory of Sports Injuries, Peking University Third Hospital, Beijing 100191; 2Medical Imaging Center, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China Received November 19, 2020; Accepted March 8, 2021 DOI: 10.3892/ijmm.2021.4922 Abstract. As an important type of programmed cell death in 1. Introduction addition to apoptosis, necroptosis occurs in a variety of patho‑ physiological processes, including infections, liver diseases, Necroptosis, an emerging field closely related to apoptosis, is a kidney injury, neurodegenerative diseases, cardiovascular non‑caspase‑dependent cell death that has been implicated in diseases, and human tumors. It can be triggered by a variety the pathological processes of various diseases. It is regulated of factors, such as tumor necrosis factor receptor and Toll‑like by various genes that cause regular and ordered cell death. receptor families, intracellular DNA and RNA sensors, and Through activating specific death signaling pathways, it shares interferon, and is mainly mediated by receptor‑interacting typical characteristics of necrosis, including loss of metabolic protein kinase 1 (RIP1), RIP3, and mixed lineage kinase function and subcellular changes (1,2). Receptor‑interacting domain‑like protein. A better understanding of the mechanism protein kinase 1 (RIP1) was the first signaling molecule of necroptosis may be useful in the development of novel drugs identified in the necrosome (3). RIP1 and RIP3 interact for necroptosis‑related diseases. -
Uncovering the Signaling Landscape Controlling Breast Cancer Cell Migration Identifies Novel Metastasis Driver Genes
ARTICLE https://doi.org/10.1038/s41467-019-11020-3 OPEN Uncovering the signaling landscape controlling breast cancer cell migration identifies novel metastasis driver genes Esmee Koedoot1,4, Michiel Fokkelman 1,4, Vasiliki-Maria Rogkoti1,4, Marcel Smid2, Iris van de Sandt1, Hans de Bont1, Chantal Pont1, Janna E. Klip1, Steven Wink 1, Mieke A. Timmermans2, Erik A.C. Wiemer2, Peter Stoilov3, John A. Foekens2, Sylvia E. Le Dévédec 1, John W.M. Martens 2 & Bob van de Water1 1234567890():,; Ttriple-negative breast cancer (TNBC) is an aggressive and highly metastatic breast cancer subtype. Enhanced TNBC cell motility is a prerequisite of TNBC cell dissemination. Here, we apply an imaging-based RNAi phenotypic cell migration screen using two highly motile TNBC cell lines (Hs578T and MDA-MB-231) to provide a repository of signaling determinants that functionally drive TNBC cell motility. We have screened ~4,200 target genes individually and discovered 133 and 113 migratory modulators of Hs578T and MDA-MB-231, respectively, which are linked to signaling networks predictive for breast cancer progression. The splicing factors PRPF4B and BUD31 and the transcription factor BPTF are essential for cancer cell migration, amplified in human primary breast tumors and associated with metastasis-free survival. Depletion of PRPF4B, BUD31 and BPTF causes primarily down regulation of genes involved in focal adhesion and ECM-interaction pathways. PRPF4B is essential for TNBC metastasis formation in vivo, making PRPF4B a candidate for further drug development. 1 Division of Drug Discovery and Safety, LACDR, Leiden University, Einsteinweg 55, Leiden 2333 CC, Netherlands. 2 Department of Medical Oncology and Cancer Genomics Netherlands, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam 3008 AE, Netherlands. -
Nuclear and Mitochondrial Genome Defects in Autisms
UC Irvine UC Irvine Previously Published Works Title Nuclear and mitochondrial genome defects in autisms. Permalink https://escholarship.org/uc/item/8vq3278q Journal Annals of the New York Academy of Sciences, 1151(1) ISSN 0077-8923 Authors Smith, Moyra Spence, M Anne Flodman, Pamela Publication Date 2009 DOI 10.1111/j.1749-6632.2008.03571.x License https://creativecommons.org/licenses/by/4.0/ 4.0 Peer reviewed eScholarship.org Powered by the California Digital Library University of California THE YEAR IN HUMAN AND MEDICAL GENETICS 2009 Nuclear and Mitochondrial Genome Defects in Autisms Moyra Smith, M. Anne Spence, and Pamela Flodman Department of Pediatrics, University of California, Irvine, California In this review we will evaluate evidence that altered gene dosage and structure im- pacts neurodevelopment and neural connectivity through deleterious effects on synap- tic structure and function, and evidence that the latter are key contributors to the risk for autism. We will review information on alterations of structure of mitochondrial DNA and abnormal mitochondrial function in autism and indications that interactions of the nuclear and mitochondrial genomes may play a role in autism pathogenesis. In a final section we will present data derived using Affymetrixtm SNP 6.0 microar- ray analysis of DNA of a number of subjects and parents recruited to our autism spectrum disorders project. We include data on two sets of monozygotic twins. Col- lectively these data provide additional evidence of nuclear and mitochondrial genome imbalance in autism and evidence of specific candidate genes in autism. We present data on dosage changes in genes that map on the X chromosomes and the Y chro- mosome. -
Genetic Variations in the PSMA6 and PSMC6 Proteasome Genes Are Associated with Multiple Sclerosis and Response to Interferon‑Β Therapy in Latvians
EXPERIMENTAL AND THERAPEUTIC MEDICINE 21: 478, 2021 Genetic variations in the PSMA6 and PSMC6 proteasome genes are associated with multiple sclerosis and response to interferon‑β therapy in Latvians NATALIA PARAMONOVA1, JOLANTA KALNINA1, KRISTINE DOKANE1, KRISTINE DISLERE1, ILVA TRAPINA1, TATJANA SJAKSTE1 and NIKOLAJS SJAKSTE1,2 1Genomics and Bioinformatics, Institute of Biology of The University of Latvia; 2Department of Medical Biochemistry of The University of Latvia, LV‑1004 Riga, Latvia Received July 8, 2020; Accepted December 8, 2020 DOI: 10.3892/etm.2021.9909 Abstract. Several polymorphisms in genes related to the Introduction ubiquitin‑proteasome system exhibit an association with pathogenesis and prognosis of various human autoimmune Multiple sclerosis (MS) is a lifelong demyelinating disease of diseases. Our previous study reported the association the central nervous system. The clinical onset of MS tends to between multiple sclerosis (MS) and the PSMA3‑rs2348071 be between the second and fourth decade of life. Similarly to polymorphism in the Latvian population. The current study other autoimmune diseases, women are affected 3‑4 times more aimed to evaluate the PSMA6 and PSMC6 genetic variations, frequently than men (1). About 10% of MS patients experience their interaction between each other and with the rs2348071, a primary progressive MS form characterized by the progres‑ on the susceptibility to MS risk and response to therapy in sion of neurological disability from the onset. In about 90% the Latvian population. PSMA6‑rs2277460, ‑rs1048990 and of MS patients, the disease undergoes the relapse‑remitting PSMC6‑rs2295826, ‑rs2295827 were genotyped in the MS MS course (RRMS); in most of these patients, the condition case/control study and analysed in terms of genotype‑protein acquires secondary progressive course (SPMS) (2). -
A Minimal Set of Internal Control Genes for Gene Expression Studies in Head
bioRxiv preprint doi: https://doi.org/10.1101/108381; this version posted February 14, 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 4.0 International license. 1 A minimal set of internal control genes for gene expression studies in head 2 and neck squamous cell carcinoma. 1 1 1 2 3 Vinayak Palve , Manisha Pareek , Neeraja M Krishnan , Gangotri Siddappa , 2 2 1,3* 4 Amritha Suresh , Moni Abraham Kuriakose and Binay Panda 5 1 6 Ganit Labs, Bio-IT Centre, Institute of Bioinformatics and Applied Biotechnology, 7 Bangalore 560100 2 8 Mazumdar Shaw Cancer Centre and Mazumdar Shaw Centre for Translational 9 Research, Bangalore 560096 3 10 Strand Life Sciences, Bangalore 560024 11 * Corresponding author: [email protected] 12 13 Abstract: 14 Background: Selection of the right reference gene(s) is crucial in the analysis and 15 interpretation of gene expression data. In head and neck cancer, studies evaluating 16 the efficacy of internal reference genes are rare. Here, we present data for a minimal 17 set of candidates as internal control genes for gene expression studies in head and 18 neck cancer. 19 Methods: We analyzed data from multiple sources (in house whole-genome gene 20 expression microarrays, n=21; TCGA RNA-seq, n=42, and published gene 21 expression studies in head and neck tumors from literature) to come up with a set of 22 genes (discovery set) for their stable expression across tumor and normal tissues. -
Mediator of DNA Damage Checkpoint 1 (MDC1) Is a Novel Estrogen Receptor Co-Regulator in Invasive 6 Lobular Carcinoma of the Breast 7 8 Evelyn K
bioRxiv preprint doi: https://doi.org/10.1101/2020.12.16.423142; this version posted December 16, 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 4.0 International license. 1 Running Title: MDC1 co-regulates ER in ILC 2 3 Research article 4 5 Mediator of DNA damage checkpoint 1 (MDC1) is a novel estrogen receptor co-regulator in invasive 6 lobular carcinoma of the breast 7 8 Evelyn K. Bordeaux1+, Joseph L. Sottnik1+, Sanjana Mehrotra1, Sarah E. Ferrara2, Andrew E. Goodspeed2,3, James 9 C. Costello2,3, Matthew J. Sikora1 10 11 +EKB and JLS contributed equally to this project. 12 13 Affiliations 14 1Dept. of Pathology, University of Colorado Anschutz Medical Campus 15 2Biostatistics and Bioinformatics Shared Resource, University of Colorado Comprehensive Cancer Center 16 3Dept. of Pharmacology, University of Colorado Anschutz Medical Campus 17 18 Corresponding author 19 Matthew J. Sikora, PhD.; Mail Stop 8104, Research Complex 1 South, Room 5117, 12801 E. 17th Ave.; Aurora, 20 CO 80045. Tel: (303)724-4301; Fax: (303)724-3712; email: [email protected]. Twitter: 21 @mjsikora 22 23 Authors' contributions 24 MJS conceived of the project. MJS, EKB, and JLS designed and performed experiments. JLS developed models 25 for the project. EKB, JLS, SM, and AEG contributed to data analysis and interpretation. SEF, AEG, and JCC 26 developed and performed informatics analyses. MJS wrote the draft manuscript; all authors read and revised the 27 manuscript and have read and approved of this version of the manuscript. -
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. -
Deubiquitinases in Cancer: New Functions and Therapeutic Options
Oncogene (2012) 31, 2373–2388 & 2012 Macmillan Publishers Limited All rights reserved 0950-9232/12 www.nature.com/onc REVIEW Deubiquitinases in cancer: new functions and therapeutic options JM Fraile1, V Quesada1, D Rodrı´guez, JMP Freije and C Lo´pez-Otı´n Departamento de Bioquı´mica y Biologı´a Molecular, Facultad de Medicina, Instituto Universitario de Oncologı´a, Universidad de Oviedo, Oviedo, Spain Deubiquitinases (DUBs) have fundamental roles in the Hunter, 2010). Consistent with the functional relevance ubiquitin system through their ability to specifically of proteases in these processes, alterations in their deconjugate ubiquitin from targeted proteins. The human structure or in the mechanisms controlling their genome encodes at least 98 DUBs, which can be grouped spatiotemporal expression patterns and activities cause into 6 families, reflecting the need for specificity in diverse pathologies such as arthritis, neurodegenerative their function. The activity of these enzymes affects the alterations, cardiovascular diseases and cancer. Accord- turnover rate, activation, recycling and localization ingly, many proteases are an important focus of of multiple proteins, which in turn is essential for attention for the pharmaceutical industry either as drug cell homeostasis, protein stability and a wide range of targets or as diagnostic and prognostic biomarkers signaling pathways. Consistent with this, altered DUB (Turk, 2006; Drag and Salvesen, 2010). function has been related to several diseases, including The recent availability of the genome sequence cancer. Thus, multiple DUBs have been classified as of different organisms has facilitated the identification oncogenes or tumor suppressors because of their regula- of their entire protease repertoire, which has been tory functions on the activity of other proteins involved in defined as degradome (Lopez-Otin and Overall, 2002). -
Selective Androgen Receptor Modulators (Sarms) And
(19) TZZ ¥6B_T (11) EP 2 222 636 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: C07D 207/08 (2006.01) C07D 207/09 (2006.01) 10.04.2013 Bulletin 2013/15 C07D 498/04 (2006.01) A61K 31/402 (2006.01) A61P 5/26 (2006.01) (21) Application number: 08865188.0 (86) International application number: (22) Date of filing: 12.12.2008 PCT/US2008/013657 (87) International publication number: WO 2009/082437 (02.07.2009 Gazette 2009/27) (54) SELECTIVE ANDROGEN RECEPTOR MODULATORS (SARMS) AND USES THEREOF SELEKTIVE ANDROGENREZEPTORMODULATOREN (SARMS) UND IHRE VERWENDUNG MODULATEURS SÉLECTIFS DU RÉCEPTEUR ANDROGÈNE (SARM) ET LEURS UTILISATIONS (84) Designated Contracting States: (74) Representative: Baldock, Sharon Claire AT BE BG CH CY CZ DE DK EE ES FI FR GB GR Boult Wade Tennant HR HU IE IS IT LI LT LU LV MC MT NL NO PL PT Verulam Gardens RO SE SI SK TR 70 Gray’s Inn Road Designated Extension States: London WC1X 8BT (GB) AL BA MK RS (56) References cited: (30) Priority: 21.12.2007 US 8731 P WO-A-02/068427 WO-A-03/090672 WO-A-2005/090282 WO-A-2006/124447 (43) Date of publication of application: WO-A-2007/015567 01.09.2010 Bulletin 2010/35 • HIGUCHI ET AL: "Potent, nonsteroidal selective (60) Divisional application: androgen receptor modulators (SARMs) based 12168231.4 / 2 489 656 on 8H-[1,4]oxazino[2,3-f]quinolin-8-ones" BIOORGANIC & MEDICINAL CHEMISTRY (73) Proprietor: Ligand Pharmaceuticals Inc. -
NPI-0052 and Γ-Radiation Induce a Synergistic Apoptotic Effect In
Frisira et al. Cell Death and Disease (2019) 10:785 https://doi.org/10.1038/s41419-019-2026-y Cell Death & Disease ARTICLE Open Access NPI-0052 and γ-radiation induce a synergistic apoptoticeffectinmedulloblastoma Eleni Frisira1, Fatima Rashid1,SwastinaNathVarma2,SaraBadodi1, Valentine Ayodele Benjamin-Ombo1, David Michod 2 and Maria Victoria Niklison-Chirou 1 Abstract Medulloblastoma (MB) is the most common malignant solid paediatric brain tumour. The standard treatment for MB is surgical resection of the tumour, radiation and chemotherapy. This therapy is associated with high morbidity and adverse side effects. Hence, more targeted and less toxic therapies are vitally needed to improve the quality of life of survivors. NPI-0052 is a novel proteasome inhibitor that irreversibly binds the 20S proteasome subunit. This compound has anti-tumour activity in metastatic solid tumours, glioblastoma and multiple myeloma with a good safety profile. Importantly, NPI-0052 has a lipophilic structure and can penetrate the blood–brain barrier, making it a suitable treatment for brain tumours. In the present study, we performed an in silico gene expression analysis to evaluate the proteasome subunit expression in MB. To evaluate the anticancer activity of NPI-0052, we used a range of MB patient- derived MB cells and cell lines. The synergistic cell death of NPI-0052 with γ-radiation was evaluated in tumour organoids derived from patient-derived MB cells. We show that high expression of proteasome subunits is a poor prognostic factor for MB patients. Also, our preclinical work demonstrated that NPI-0052 can inhibit proteasome activity and activate apoptosis in MB cells. Moreover, we observe that NPI-0052 has a synergistic apoptotic effect with γ-radiation, a component of the current MB therapy. -
Proteasome System of Protein Degradation and Processing
ISSN 0006-2979, Biochemistry (Moscow), 2009, Vol. 74, No. 13, pp. 1411-1442. © Pleiades Publishing, Ltd., 2009. Original Russian Text © A. V. Sorokin, E. R. Kim, L. P. Ovchinnikov, 2009, published in Uspekhi Biologicheskoi Khimii, 2009, Vol. 49, pp. 3-76. REVIEW Proteasome System of Protein Degradation and Processing A. V. Sorokin*, E. R. Kim, and L. P. Ovchinnikov Institute of Protein Research, Russian Academy of Sciences, 142290 Pushchino, Moscow Region, Russia; E-mail: [email protected]; [email protected] Received February 5, 2009 Abstract—In eukaryotic cells, degradation of most intracellular proteins is realized by proteasomes. The substrates for pro- teolysis are selected by the fact that the gate to the proteolytic chamber of the proteasome is usually closed, and only pro- teins carrying a special “label” can get into it. A polyubiquitin chain plays the role of the “label”: degradation affects pro- teins conjugated with a ubiquitin (Ub) chain that consists at minimum of four molecules. Upon entering the proteasome channel, the polypeptide chain of the protein unfolds and stretches along it, being hydrolyzed to short peptides. Ubiquitin per se does not get into the proteasome, but, after destruction of the “labeled” molecule, it is released and labels another molecule. This process has been named “Ub-dependent protein degradation”. In this review we systematize current data on the Ub–proteasome system, describe in detail proteasome structure, the ubiquitination system, and the classical ATP/Ub- dependent mechanism of protein degradation, as well as try to focus readers’ attention on the existence of alternative mech- anisms of proteasomal degradation and processing of proteins. -
Supplementary Figures 1-14 and Supplementary References
SUPPORTING INFORMATION Spatial Cross-Talk Between Oxidative Stress and DNA Replication in Human Fibroblasts Marko Radulovic,1,2 Noor O Baqader,1 Kai Stoeber,3† and Jasminka Godovac-Zimmermann1* 1Division of Medicine, University College London, Center for Nephrology, Royal Free Campus, Rowland Hill Street, London, NW3 2PF, UK. 2Insitute of Oncology and Radiology, Pasterova 14, 11000 Belgrade, Serbia 3Research Department of Pathology and UCL Cancer Institute, Rockefeller Building, University College London, University Street, London WC1E 6JJ, UK †Present Address: Shionogi Europe, 33 Kingsway, Holborn, London WC2B 6UF, UK TABLE OF CONTENTS 1. Supplementary Figures 1-14 and Supplementary References. Figure S-1. Network and joint spatial razor plot for 18 enzymes of glycolysis and the pentose phosphate shunt. Figure S-2. Correlation of SILAC ratios between OXS and OAC for proteins assigned to the SAME class. Figure S-3. Overlap matrix (r = 1) for groups of CORUM complexes containing 19 proteins of the 49-set. Figure S-4. Joint spatial razor plots for the Nop56p complex and FIB-associated complex involved in ribosome biogenesis. Figure S-5. Analysis of the response of emerin nuclear envelope complexes to OXS and OAC. Figure S-6. Joint spatial razor plots for the CCT protein folding complex, ATP synthase and V-Type ATPase. Figure S-7. Joint spatial razor plots showing changes in subcellular abundance and compartmental distribution for proteins annotated by GO to nucleocytoplasmic transport (GO:0006913). Figure S-8. Joint spatial razor plots showing changes in subcellular abundance and compartmental distribution for proteins annotated to endocytosis (GO:0006897). Figure S-9. Joint spatial razor plots for 401-set proteins annotated by GO to small GTPase mediated signal transduction (GO:0007264) and/or GTPase activity (GO:0003924).