DOCSLIB.ORG

Heat Shock Proteins and Ovarian Cancer: Important Roles and Therapeutic Opportunities

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Heat Shock Proteins and Ovarian Cancer: Important Roles and Therapeutic Opportunities cancers Review Heat Shock Proteins and Ovarian Cancer: Important Roles and Therapeutic Opportunities Abdullah Hoter 1,2 and Hassan Y. Naim 2,* 1 Department of Biochemistry and Chemistry of Nutrition, Faculty of Veterinary Medicine, Cairo University, Giza 12211, Egypt; [email protected] 2 Department of Physiological Chemistry, University of Veterinary Medicine Hannover, 30559 Hannover, Germany * Correspondence: [email protected]; Tel.: +49-511-953-8780; Fax: +49-511-953-8585 Received: 29 August 2019; Accepted: 16 September 2019; Published: 18 September 2019 Abstract: Ovarian cancer is a serious cause of death in gynecological oncology. Delayed diagnosis and poor survival rates associated with late stages of the disease are major obstacles against treatment efforts. Heat shock proteins (HSPs) are stress responsive molecules known to be crucial in many cancer types including ovarian cancer. Clusterin (CLU), a unique chaperone protein with analogous oncogenic criteria to HSPs, has also been proven to confer resistance to anti-cancer drugs. Indeed, these chaperone molecules have been implicated in diagnosis, prognosis, metastasis and aggressiveness of various cancers. However, relative to other cancers, there is limited body of knowledge about the molecular roles of these chaperones in ovarian cancer. In the current review, we shed light on the diverse roles of HSPs as well as related chaperone proteins like CLU in the pathogenesis of ovarian cancer and elucidate their potential as effective drug targets. Keywords: ovarian cancer; heat shock proteins (HSPs); clusterin; therapeutic resistance; HSP inhibitors; ovarian cancer treatment 1. Introduction 1.1. Ovarian Cancer Is a Serious Problem in Gynaecological Oncology Ovarian cancer (OC) is a major life-threatening problem in the field of gynecological oncology. Globally, it stands as the foremost cause of death in women accounting for approximately 239,000 newly diagnosed cases and over 150,000 deaths per year [1]. Recent reports in the United States estimated 22,240 new cases with ovarian cancer and 14,070 deaths owing to the disease [2]. Notably, the highest incidence and mortality rates have been linked to Eastern and Central Europe [1]. Therefore, great efforts are required to improve the therapeutic outcomes for diseased women. Additionally, thorough understanding of the molecular mechanisms and key elements contributing the disease is substantial in combating ovarian cancer [3]. Indeed, ovarian tumors can arise from three ovarian cell types namely, surface epithelium, sex cord stromal cells and germ cells [4]. Epithelial tumors account for 90% of ovarian malignancies while non-epithelial tumors including sex cord stromal and germ cell tumors represent 10% of the diagnosed cases. Epithelial ovarian cancer (EOC) are histologically categorized into serous, endometrioid, clear cell and mucinous carcinomas; the serous type itself is subclassified into high grade serous carcinoma (HGSC), low grade serous carcinoma (LGSC) and serous tubal intraepithelial carcinoma (STIC) [3] (a brief classification of OC histology is illustrated in Figure1). Cancers 2019, 11, 1389; doi:10.3390/cancers11091389 www.mdpi.com/journal/cancers Cancers 2019, 11, 1389 2 of 29 Cancers 2019, 11, x FOR PEER REVIEW 2 of 29 FigureFigure 1.1. HistologicalHistological stratificationstratification ofof ovarianovarian cancercancer aa.(. (a)) HighHigh gradegrade serousserous carcinomacarcinoma (HGSC)(HGSC) isis distinguisheddistinguished byby increasedincreased nuclearnuclear atypia,atypia, highhigh nuclear-to-cytoplasmicnuclear-to-cytoplasmic ratio and abundantabundant mitosis. ((bb)) SerousSerous tubaltubal intraepithelialintraepithelial carcinomacarcinoma (STIC)(STIC) resemblesresembles HGSCHGSC inin manymany morphologicalmorphological aspectsaspects suchsuch asas severesevere atypia,atypia, defectivedefective cellularcellular polaritypolarity andand mitoses.mitoses. Therefore, STIC is believedbelieved toto bebe aa precursorprecursor ofof HGSC.HGSC. ((cc)) LowLow gradegrade serousserous carcinomacarcinoma (LGSC)(LGSC) isis characterizedcharacterized byby increasedincreased papillae,papillae, mildmild nuclearnuclear atypia atypia and and low low nuclear-to-cytoplasmic nuclear-to-cytoplasmic ratio. ratio. (d) Clear(d) Clear cell carcinoma cell carcinoma exhibits exhibits large tumor large celltumor sizes cell and sizes frequent and clearingfrequent of clearing the cytoplasm of the togethercytoplasm with together stromal with hyalinization. stromal hyalinization. (e) Endometrioid (e) adenocarcinomaEndometrioid adenocarcinom can be differentiateda can be by glanddifferentiated formation by thatgland recapitulates formation endometrial that recapitulates glands. Thisendometrial type is furtherglands. categorized This type is according further categorized to cellular architectureaccording to and cellular nuclear architecture atypia. ( fand) Mucinous nuclear adenocarcinomaatypia. (f) Mucinous is characterized adenocarcinoma by increased is characterized cellular mucin by increased and formation cellular of goblet mucin cells. anda formationHistological of imagesgoblet cells. are adapted a Histological from Nature images Reviews are adapted Disease from Primers Nature [ 3Reviews]. Disease Primers [3]. OCOC isis oftenoften diagnoseddiagnosed atat relativelyrelatively oldold ageage ofof life,life, withwith aa medianmedian ageage ofof 6363 yearsyears inin thethe US womenwomen populationpopulation (https:(https://seer.cancer.gov/statfacts/html/ovary.html//seer.cancer.gov/statfacts/html/ovary.html). In). addition,In addition, current current data data show show that 59%that of59% the of cases the cases have have metastatic metastatic forms forms of theof the disease, disease while, while only only 15% 15% are are diagnosed diagnosed at at thethe locallocal stage. OfOf particularparticular importance,importance, earlyearly detectiondetection ofof ovarian malignancies is associated with higher cure rates, withwith aa five-yearfive-year survivalsurvival exceedingexceeding 92%92% forfor localizedlocalized ovarianovarian cancer,cancer, whereaswhereas latelate stagestage diagnosisdiagnosis ofof thethe metastaticmetastatic diseasedisease lowerslowers curecure ratesrates toto 20%20% [[5,6].5,6]. TheThe standardstandard treatment treatment protocol protocol for humanfor human ovarian ovarian cancer cancer includes includes maximal maximal cytoreductive cytoreductive surgical debulkingsurgical debulking followed byfoll theowed platinum-based by the platinum chemotherapy.-based chemotherapy. Concurrent with Concurrent surgical cytoreduction,with surgical stagingcytoreduction, of the disease staging remains of the importantdisease remains [7,8]. Current important therapeutic [7,8]. Current regimens therapeutic to the first-line regimens treatment to the whichfirst‑line involve treatment bevacizumab which involve and bevacizumab paclitaxel have and shown paclitaxel improved have shown survival improved among survival patients among with OCpatients [7,9]. with Unfortunately, OC [7,9]. despiteUnfortunately, initial remarkable despite initial response remarkable to chemotherapy, response the to majority chemotherapy, of advanced the OCmajority cases of recur advanced after primary OC cases drug recur treatment after primary with drug fatal outcometreatment [ 10with]. According fatal outcome to Ovarian [10]. According Cancer Researchto Ovarian Alliance Cancer (OCRA),Research currentAlliance reports (OCRA), show current that re patientsports show diagnosed that patients at stages diagnosed I and II at have stages a recurrenceI and II have chance a recurrence of 10% and chance 30%, of respectively, 10% and 30%, whereas respectively the chance, whereas of recurrence the chance in those of recurrence of stage IIIin andthose IV of ranges stage betweenIII and IV 70% ranges and 95%between (https: 70%//ocrahope.org and 95% (https://ocrahope.org/patients/about/patients/about-ovarian-cancer/recurrence-ovarian/).- cancer/recurrMultipleence/ treatment). approaches have been adapted for management of relapsed ovarian cancer. For instanceMultiple, agents treatment targeting approaches angiogenesis have been include adapted Bevacizumab, for management a monoclonal of relapsed antibody ovarian that cancer. binds humanFor instance, vascular agents endothelial targeting growthangiogenesis factor include (VEGF) Bevacizumab, and inhibits itsa monoclonal activity. Cediranib antibody isthat an binds oral VEGFhuman receptor vascular and endothelial c-KIT inhibitor growth factor that displays (VEGF) antitumorand inhibits activity its activity. in relapsed Cediranib EOC is an in oral phase VEGF I/II studies.receptor Trebananiband c-KIT inhibitor is a peptide that thatdisplays suppresses antitumor angiogenesis activity in by relapsed inhibiting EOC angiopoietin-1 in phase I/II studies. and -2. Moreover,Trebananib other is a treatmentpeptide that strategies suppresses involve angiogenesis PARP inhibitors by inhibiting (PARPi) angiopoietin which render-1 PARPand -2. enzymes Moreover, no moreother capabletreatment of performingstrategies involve DNA repairPARP processesinhibitors and (PARPi) ultimately which leading render toPARP synthetic enzymes lethality no more [11]. Thesecapable PARP of performing inhibitors include DNA repair olaparib processes (AZD2281), and ultimately niraparib (MK4827),leading to rucaparibsynthetic (CO338,lethality AGO14699,[11]. These andPARP PF01367338), inhibitors veliparibinclude olaparib (ABT-888) (AZD2281), and talazoparib
Load more

Recommended publications
  • Deregulated Gene Expression Pathways in Myelodysplastic Syndrome Hematopoietic Stem Cells
    Leukemia (2010) 24, 756–764 & 2010 Macmillan Publishers Limited All rights reserved 0887-6924/10 $32.00 www.nature.com/leu ORIGINAL ARTICLE Deregulated gene expression pathways in myelodysplastic syndrome hematopoietic stem cells A Pellagatti1, M Cazzola2, A Giagounidis3, J Perry1, L Malcovati2, MG Della Porta2,MJa¨dersten4, S Killick5, A Verma6, CJ Norbury7, E Hellstro¨m-Lindberg4, JS Wainscoat1 and J Boultwood1 1LRF Molecular Haematology Unit, NDCLS, John Radcliffe Hospital, Oxford, UK; 2Department of Hematology Oncology, University of Pavia Medical School, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; 3Medizinische Klinik II, St Johannes Hospital, Duisburg, Germany; 4Division of Hematology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden; 5Department of Haematology, Royal Bournemouth Hospital, Bournemouth, UK; 6Albert Einstein College of Medicine, Bronx, NY, USA and 7Sir William Dunn School of Pathology, University of Oxford, Oxford, UK To gain insight into the molecular pathogenesis of the the World Health Organization.6,7 Patients with refractory myelodysplastic syndromes (MDS), we performed global gene anemia (RA) with or without ringed sideroblasts, according to expression profiling and pathway analysis on the hemato- poietic stem cells (HSC) of 183 MDS patients as compared with the the French–American–British classification, were subdivided HSC of 17 healthy controls. The most significantly deregulated based on the presence or absence of multilineage dysplasia. In pathways in MDS include interferon signaling, thrombopoietin addition, patients with RA with excess blasts (RAEB) were signaling and the Wnt pathways. Among the most signifi- subdivided into two categories, RAEB1 and RAEB2, based on the cantly deregulated gene pathways in early MDS are immuno- percentage of bone marrow blasts.
    [Show full text]
  • Computational Genome-Wide Identification of Heat Shock Protein Genes in the Bovine Genome [Version 1; Peer Review: 2 Approved, 1 Approved with Reservations]
    F1000Research 2018, 7:1504 Last updated: 08 AUG 2021 RESEARCH ARTICLE Computational genome-wide identification of heat shock protein genes in the bovine genome [version 1; peer review: 2 approved, 1 approved with reservations] Oyeyemi O. Ajayi1,2, Sunday O. Peters3, Marcos De Donato2,4, Sunday O. Sowande5, Fidalis D.N. Mujibi6, Olanrewaju B. Morenikeji2,7, Bolaji N. Thomas 8, Matthew A. Adeleke 9, Ikhide G. Imumorin2,10,11 1Department of Animal Breeding and Genetics, Federal University of Agriculture, Abeokuta, Nigeria 2International Programs, College of Agriculture and Life Sciences, Cornell University, Ithaca, NY, 14853, USA 3Department of Animal Science, Berry College, Mount Berry, GA, 30149, USA 4Departamento Regional de Bioingenierias, Tecnologico de Monterrey, Escuela de Ingenieria y Ciencias, Queretaro, Mexico 5Department of Animal Production and Health, Federal University of Agriculture, Abeokuta, Nigeria 6Usomi Limited, Nairobi, Kenya 7Department of Animal Production and Health, Federal University of Technology, Akure, Nigeria 8Department of Biomedical Sciences, Rochester Institute of Technology, Rochester, NY, 14623, USA 9School of Life Sciences, University of KwaZulu-Natal, Durban, 4000, South Africa 10School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA, 30032, USA 11African Institute of Bioscience Research and Training, Ibadan, Nigeria v1 First published: 20 Sep 2018, 7:1504 Open Peer Review https://doi.org/10.12688/f1000research.16058.1 Latest published: 20 Sep 2018, 7:1504 https://doi.org/10.12688/f1000research.16058.1 Reviewer Status Invited Reviewers Abstract Background: Heat shock proteins (HSPs) are molecular chaperones 1 2 3 known to bind and sequester client proteins under stress. Methods: To identify and better understand some of these proteins, version 1 we carried out a computational genome-wide survey of the bovine 20 Sep 2018 report report report genome.
    [Show full text]
  • Gene Targeting Therapies (Roy Alcalay)
    Recent Developments in Gene - Targeted Therapies for Parkinson’s Disease Roy Alcalay, MD, MS Alfred and Minnie Bressler Associate Professor of Neurology Division of Movement Disorders Columbia University Medical Center Disclosures Funding: Dr. Alcalay is funded by the National Institutes of Health, the DOD, the Michael J. Fox Foundation and the Parkinson’s Foundation. Dr. Alcalay receives consultation fees from Genzyme/Sanofi, Restorbio, Janssen, and Roche. Gene Localizations Identified in PD Gene Symbol Protein Transmission Chromosome PARK1 SNCA α-synuclein AD 4q22.1 PARK2 PRKN parkin (ubiquitin ligase) AR 6q26 PARK3 ? ? AD 2p13 PARK4 SNCA triplication α-synuclein AD 4q22.1 PARK5 UCH-L1 ubiquitin C-terminal AD 4p13 hydrolase-L1 PARK6 PINK1 PTEN-induced kinase 1 AR 1p36.12 PARK7 DJ-1 DJ-1 AR 1p36.23 PARK8 LRRK2 leucine rich repeat kinase 2 AD 12q12 PARK9 ATP13A2 lysosomal ATPase AR 1p36.13 PARK10 ? ? (Iceland) AR 1p32 PARK11 GIGYF2 GRB10-interacting GYF protein 2 AD 2q37.1 PARK12 ? ? X-R Xq21-q25 PARK13 HTRA2 serine protease AD 2p13.1 PARK14 PLA2G6 phospholipase A2 (INAD) AR 22q13.1 PARK15 FBXO7 F-box only protein 7 AR 22q12.3 PARK16 ? Discovered by GWAS ? 1q32 PARK17 VPS35 vacuolar protein sorting 35 AD 16q11.2 PARK18 EIF4G1 initiation of protein synth AD 3q27.1 PARK19 DNAJC6 auxilin AR 1p31.3 PARK20 SYNJ1 synaptojanin 1 AR 21q22.11 PARK21 DNAJC13 8/RME-8 AD 3q22.1 PARK22 CHCHD2 AD 7p11.2 PARK23 VPS13C AR 15q22 Gene Localizations Identified in PD Disorder Symbol Protein Transmission Chromosome PD GBA β-glucocerebrosidase AD 1q21 SCA2
    [Show full text]
  • C-Terminal HSP90 Inhibitors Block the HSP90:HIF-1Α Interaction and Inhibit the Cellular Hypoxic Response
    bioRxiv preprint doi: https://doi.org/10.1101/521989; this version posted January 24, 2019. 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. C-terminal HSP90 Inhibitors Block the HSP90:HIF-1α Interaction and Inhibit the Cellular Hypoxic Response Nalin Katariaa, Bernadette Kerra, Samantha S. Zaiterb, Shelli McAlpineb and Kristina M Cooka† a. University of Sydney, Faculty of Medicine and Health, Charles Perkins Centre, Sydney, Australia. b. School of Chemistry, University of New South Wales, Sydney, Australia. † To whom correspondence should be addressed: Kristina M Cook, Charles Perkins Centre, University of Sydney, Sydney, NSW, Australia 2006; [email protected]; Tel: +61 286274858. Hypoxia Inducible Factor (HIF) is a transcription factor cancer cells known as a heat shock response (HSR)12. The activated by low oxygen, which is common in solid compounds also have poor selectivity for HSP9013,14. tumours. HIF controls the expression of genes involved in C-terminus inhibitors of HSP90 (SM molecules)11 act in a angiogenesis, chemotherapy resistance and metastasis. The selective manner, and in contrast to the N-terminus chaperone HSP90 (Heat Shock Protein 90) stabilizes the inhibitors, they do not induce a heat shock response13,15. subunit HIF-1α and prevents degradation. Previously Although the SM molecules block all co-chaperones that identified HSP90 inhibitors bind to the N-terminal pocket bind to the C-terminus of HSP90 and inhibit HSP90 of HSP90 which blocks binding to HIF-1α, and produces function16,17, there is no data discussing whether C- HIF-1α degradation.
    [Show full text]
  • Defining Functional Interactions During Biogenesis of Epithelial Junctions
    ARTICLE Received 11 Dec 2015 | Accepted 13 Oct 2016 | Published 6 Dec 2016 | Updated 5 Jan 2017 DOI: 10.1038/ncomms13542 OPEN Defining functional interactions during biogenesis of epithelial junctions J.C. Erasmus1,*, S. Bruche1,*,w, L. Pizarro1,2,*, N. Maimari1,3,*, T. Poggioli1,w, C. Tomlinson4,J.Lees5, I. Zalivina1,w, A. Wheeler1,w, A. Alberts6, A. Russo2 & V.M.M. Braga1 In spite of extensive recent progress, a comprehensive understanding of how actin cytoskeleton remodelling supports stable junctions remains to be established. Here we design a platform that integrates actin functions with optimized phenotypic clustering and identify new cytoskeletal proteins, their functional hierarchy and pathways that modulate E-cadherin adhesion. Depletion of EEF1A, an actin bundling protein, increases E-cadherin levels at junctions without a corresponding reinforcement of cell–cell contacts. This unexpected result reflects a more dynamic and mobile junctional actin in EEF1A-depleted cells. A partner for EEF1A in cadherin contact maintenance is the formin DIAPH2, which interacts with EEF1A. In contrast, depletion of either the endocytic regulator TRIP10 or the Rho GTPase activator VAV2 reduces E-cadherin levels at junctions. TRIP10 binds to and requires VAV2 function for its junctional localization. Overall, we present new conceptual insights on junction stabilization, which integrate known and novel pathways with impact for epithelial morphogenesis, homeostasis and diseases. 1 National Heart and Lung Institute, Faculty of Medicine, Imperial College London, London SW7 2AZ, UK. 2 Computing Department, Imperial College London, London SW7 2AZ, UK. 3 Bioengineering Department, Faculty of Engineering, Imperial College London, London SW7 2AZ, UK. 4 Department of Surgery & Cancer, Faculty of Medicine, Imperial College London, London SW7 2AZ, UK.
    [Show full text]
  • Identification and Characterization of TPRKB Dependency in TP53 Deficient Cancers
    Identification and Characterization of TPRKB Dependency in TP53 Deficient Cancers. by Kelly Kennaley A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy (Molecular and Cellular Pathology) in the University of Michigan 2019 Doctoral Committee: Associate Professor Zaneta Nikolovska-Coleska, Co-Chair Adjunct Associate Professor Scott A. Tomlins, Co-Chair Associate Professor Eric R. Fearon Associate Professor Alexey I. Nesvizhskii Kelly R. Kennaley [email protected] ORCID iD: 0000-0003-2439-9020 © Kelly R. Kennaley 2019 Acknowledgements I have immeasurable gratitude for the unwavering support and guidance I received throughout my dissertation. First and foremost, I would like to thank my thesis advisor and mentor Dr. Scott Tomlins for entrusting me with a challenging, interesting, and impactful project. He taught me how to drive a project forward through set-backs, ask the important questions, and always consider the impact of my work. I’m truly appreciative for his commitment to ensuring that I would get the most from my graduate education. I am also grateful to the many members of the Tomlins lab that made it the supportive, collaborative, and educational environment that it was. I would like to give special thanks to those I’ve worked closely with on this project, particularly Dr. Moloy Goswami for his mentorship, Lei Lucy Wang, Dr. Sumin Han, and undergraduate students Bhavneet Singh, Travis Weiss, and Myles Barlow. I am also grateful for the support of my thesis committee, Dr. Eric Fearon, Dr. Alexey Nesvizhskii, and my co-mentor Dr. Zaneta Nikolovska-Coleska, who have offered guidance and critical evaluation since project inception.
    [Show full text]
  • 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]
  • Protein Identities in Evs Isolated from U87-MG GBM Cells As Determined by NG LC-MS/MS
    Protein identities in EVs isolated from U87-MG GBM cells as determined by NG LC-MS/MS. No. Accession Description Σ Coverage Σ# Proteins Σ# Unique Peptides Σ# Peptides Σ# PSMs # AAs MW [kDa] calc. pI 1 A8MS94 Putative golgin subfamily A member 2-like protein 5 OS=Homo sapiens PE=5 SV=2 - [GG2L5_HUMAN] 100 1 1 7 88 110 12,03704523 5,681152344 2 P60660 Myosin light polypeptide 6 OS=Homo sapiens GN=MYL6 PE=1 SV=2 - [MYL6_HUMAN] 100 3 5 17 173 151 16,91913397 4,652832031 3 Q6ZYL4 General transcription factor IIH subunit 5 OS=Homo sapiens GN=GTF2H5 PE=1 SV=1 - [TF2H5_HUMAN] 98,59 1 1 4 13 71 8,048185945 4,652832031 4 P60709 Actin, cytoplasmic 1 OS=Homo sapiens GN=ACTB PE=1 SV=1 - [ACTB_HUMAN] 97,6 5 5 35 917 375 41,70973209 5,478027344 5 P13489 Ribonuclease inhibitor OS=Homo sapiens GN=RNH1 PE=1 SV=2 - [RINI_HUMAN] 96,75 1 12 37 173 461 49,94108966 4,817871094 6 P09382 Galectin-1 OS=Homo sapiens GN=LGALS1 PE=1 SV=2 - [LEG1_HUMAN] 96,3 1 7 14 283 135 14,70620005 5,503417969 7 P60174 Triosephosphate isomerase OS=Homo sapiens GN=TPI1 PE=1 SV=3 - [TPIS_HUMAN] 95,1 3 16 25 375 286 30,77169764 5,922363281 8 P04406 Glyceraldehyde-3-phosphate dehydrogenase OS=Homo sapiens GN=GAPDH PE=1 SV=3 - [G3P_HUMAN] 94,63 2 13 31 509 335 36,03039959 8,455566406 9 Q15185 Prostaglandin E synthase 3 OS=Homo sapiens GN=PTGES3 PE=1 SV=1 - [TEBP_HUMAN] 93,13 1 5 12 74 160 18,68541938 4,538574219 10 P09417 Dihydropteridine reductase OS=Homo sapiens GN=QDPR PE=1 SV=2 - [DHPR_HUMAN] 93,03 1 1 17 69 244 25,77302971 7,371582031 11 P01911 HLA class II histocompatibility antigen,
    [Show full text]
  • Α Are Regulated by Heat Shock Protein 90
    The Levels of Retinoic Acid-Inducible Gene I Are Regulated by Heat Shock Protein 90- α Tomoh Matsumiya, Tadaatsu Imaizumi, Hidemi Yoshida, Kei Satoh, Matthew K. Topham and Diana M. Stafforini This information is current as of October 2, 2021. J Immunol 2009; 182:2717-2725; ; doi: 10.4049/jimmunol.0802933 http://www.jimmunol.org/content/182/5/2717 Downloaded from References This article cites 44 articles, 19 of which you can access for free at: http://www.jimmunol.org/content/182/5/2717.full#ref-list-1 Why The JI? Submit online. http://www.jimmunol.org/ • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average by guest on October 2, 2021 Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2009 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology The Levels of Retinoic Acid-Inducible Gene I Are Regulated by Heat Shock Protein 90-␣1 Tomoh Matsumiya,*‡ Tadaatsu Imaizumi,‡ Hidemi Yoshida,‡ Kei Satoh,‡ Matthew K. Topham,*† and Diana M. Stafforini2*† Retinoic acid-inducible gene I (RIG-I) is an intracellular pattern recognition receptor that plays important roles during innate immune responses to viral dsRNAs.
    [Show full text]
  • 1 Supporting Information for a Microrna Network Regulates
    Supporting Information for A microRNA Network Regulates Expression and Biosynthesis of CFTR and CFTR-ΔF508 Shyam Ramachandrana,b, Philip H. Karpc, Peng Jiangc, Lynda S. Ostedgaardc, Amy E. Walza, John T. Fishere, Shaf Keshavjeeh, Kim A. Lennoxi, Ashley M. Jacobii, Scott D. Rosei, Mark A. Behlkei, Michael J. Welshb,c,d,g, Yi Xingb,c,f, Paul B. McCray Jr.a,b,c Author Affiliations: Department of Pediatricsa, Interdisciplinary Program in Geneticsb, Departments of Internal Medicinec, Molecular Physiology and Biophysicsd, Anatomy and Cell Biologye, Biomedical Engineeringf, Howard Hughes Medical Instituteg, Carver College of Medicine, University of Iowa, Iowa City, IA-52242 Division of Thoracic Surgeryh, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Canada-M5G 2C4 Integrated DNA Technologiesi, Coralville, IA-52241 To whom correspondence should be addressed: Email: [email protected] (M.J.W.); yi- [email protected] (Y.X.); Email: [email protected] (P.B.M.) This PDF file includes: Materials and Methods References Fig. S1. miR-138 regulates SIN3A in a dose-dependent and site-specific manner. Fig. S2. miR-138 regulates endogenous SIN3A protein expression. Fig. S3. miR-138 regulates endogenous CFTR protein expression in Calu-3 cells. Fig. S4. miR-138 regulates endogenous CFTR protein expression in primary human airway epithelia. Fig. S5. miR-138 regulates CFTR expression in HeLa cells. Fig. S6. miR-138 regulates CFTR expression in HEK293T cells. Fig. S7. HeLa cells exhibit CFTR channel activity. Fig. S8. miR-138 improves CFTR processing. Fig. S9. miR-138 improves CFTR-ΔF508 processing. Fig. S10. SIN3A inhibition yields partial rescue of Cl- transport in CF epithelia.
    [Show full text]
  • Holdase Activity of Secreted Hsp70 Masks Amyloid-Β42 Neurotoxicity in Drosophila
    Holdase activity of secreted Hsp70 masks amyloid-β42 neurotoxicity in Drosophila Pedro Fernandez-Funeza,b,c,1, Jonatan Sanchez-Garciaa, Lorena de Menaa, Yan Zhanga, Yona Levitesb, Swati Kharea, Todd E. Goldea,b, and Diego E. Rincon-Limasa,b,c,1 aDepartment of Neurology, McKnight Brain Institute, University of Florida, Gainesville, FL 32611; bDepartment of Neuroscience, Center for Translational Research on Neurodegenerative Diseases, University of Florida, Gainesville, FL 32611; and cGenetics Institute, University of Florida, Gainesville, FL 32611 Edited by Nancy M. Bonini, University of Pennsylvania, Philadelphia, PA, and approved July 11, 2016 (received for review May 25, 2016) Alzheimer’s disease (AD) is the most prevalent of a large group of cell-free systems by dissociating preformed oligomers but not fi- related proteinopathies for which there is currently no cure. Here, we brils, suggesting that Hsp70 targets oligomeric intermediates (18). used Drosophila to explore a strategy to block Aβ42 neurotoxicity More recent in vitro studies show that Hsp70 and other chaperones through engineering of the Heat shock protein 70 (Hsp70), a chap- promote the aggregation of oligomers into less toxic species (19). erone that has demonstrated neuroprotective activity against several Also, Hsp70 demonstrates neuroprotection against intracellular intracellular amyloids. To target its protective activity against extra- Aβ42 in primary cultures (20), whereas down-regulation of Hsp70 cellular Aβ42, we added a signal peptide to Hsp70. This secreted form leads to increased protein aggregation in transgenic worms of Hsp70 (secHsp70) suppresses Aβ42 neurotoxicity in adult eyes, expressing intracellular Aβ42 (21). A recent study in a transgenic reduces cell death, protects the structural integrity of adult neurons, mouse model of AD overexpressing the Amyloid precursor pro- alleviates locomotor dysfunction, and extends lifespan.
    [Show full text]
  • At Elevated Temperatures, Heat Shock Protein Genes Show Altered Ratios Of
    EXPERIMENTAL AND THERAPEUTIC MEDICINE 22: 900, 2021 At elevated temperatures, heat shock protein genes show altered ratios of different RNAs and expression of new RNAs, including several novel HSPB1 mRNAs encoding HSP27 protein isoforms XIA GAO1,2, KEYIN ZHANG1,2, HAIYAN ZHOU3, LUCAS ZELLMER4, CHENGFU YUAN5, HAI HUANG6 and DEZHONG JOSHUA LIAO2,6 1Department of Pathology, Guizhou Medical University Hospital; 2Key Lab of Endemic and Ethnic Diseases of The Ministry of Education of China in Guizhou Medical University; 3Clinical Research Center, Guizhou Medical University Hospital, Guiyang, Guizhou 550004, P.R. China; 4Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; 5Department of Biochemistry, China Three Gorges University, Yichang, Hubei 443002; 6Center for Clinical Laboratories, Guizhou Medical University Hospital, Guiyang, Guizhou 550004, P.R. China Received December 16, 2020; Accepted May 10, 2021 DOI: 10.3892/etm.2021.10332 Abstract. Heat shock proteins (HSP) serve as chaperones genes may engender multiple protein isoforms. These results to maintain the physiological conformation and function of collectively suggested that, besides increasing their expres‑ numerous cellular proteins when the ambient temperature is sion, certain HSP and associated genes also use alternative increased. To determine how accurate the general assumption transcription start sites to produce multiple RNA transcripts that HSP gene expression is increased in febrile situations is, and use alternative splicing of a transcript to produce multiple the RNA levels of the HSF1 (heat shock transcription factor 1) mature RNAs, as important mechanisms for responding to an gene and certain HSP genes were determined in three cell increased ambient temperature in vitro. lines cultured at 37˚C or 39˚C for three days.
    [Show full text]