DOCSLIB.ORG

Role of Proteasomes in Inflammation

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Role of Proteasomes in Inflammation Journal of Clinical Medicine Review Role of Proteasomes in Inflammation Carl Christoph Goetzke 1,2,3,* , Frédéric Ebstein 4 and Tilmann Kallinich 1,2,3,5,* 1 Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Department of Pediatrics, Division of Pulmonology, Immunology and Critical Care Medicine, Augustenburger Platz 1, 13353 Berlin, Germany 2 Berlin Institute of Health at Charité–Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany 3 Deutsches Rheumaforschungszentrum, Charitéplatz 1, 10117 Berlin, Germany 4 Universitätsmedizin Greifswald, Institute of Medical Biochemistry and Molecular Biology, 7475 Greifswald, Germany; [email protected] 5 Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, Center for Chronically Sick Children, Augustenburger Platz 1, 13353 Berlin, Germany * Correspondence: [email protected] (C.C.G.); [email protected] (T.K.) Abstract: The ubiquitin–proteasome system (UPS) is involved in multiple cellular functions including the regulation of protein homeostasis, major histocompatibility (MHC) class I antigen processing, cell cycle proliferation and signaling. In humans, proteasome loss-of-function mutations result in autoinflammation dominated by a prominent type I interferon (IFN) gene signature. These genomic alterations typically cause the development of proteasome-associated autoinflammatory syndromes (PRAAS) by impairing proteasome activity and perturbing protein homeostasis. However, an abnormal increased proteasomal activity can also be found in other human inflammatory diseases. In this review, we cast a light on the different clinical aspects of proteasomal activity in human disease and summarize the currently studied therapeutic approaches. Keywords: proteasome; inflammation; autoinflammation; autoimmune; proteasome-associated Citation: Goetzke, C.C.; Ebstein, F.; autoinflammatory syndrome Kallinich, T. Role of Proteasomes in Inflammation. J. Clin. Med. 2021, 10, 1783. https://doi.org/10.3390/ jcm10081783 1. The Ubiquitin–Proteasome System The ubiquitin–proteasome system (UPS) is the most important intracellular non- Academic Editors: Eugen Feist and lysosomal pathway for protein breakdown in eukaryotic cells [1–3]. As such, it plays a Burkhard Möller critical role in preserving protein homeostasis and protecting the cells from harmful protein aggregation which would compromise cell integrity and function [4,5]. Received: 14 March 2021 The UPS is a highly complex mechanism with well over 1000 different genes in- Accepted: 14 April 2021 Published: 20 April 2021 volved [6], about only 50 of which encode proteins serving proteasome function [7]. The vast majority of the remaining UPS genes encode components involved in the selective Publisher’s Note: MDPI stays neutral modification of intracellular substrates with the ubiquitin molecule for recognition and with regard to jurisdictional claims in subsequent degradation by proteasomes [8,9]. The covalent attachment of ubiquitin to published maps and institutional affil- target proteins is mediated by a cascade reaction involving three enzymes. In the first step, iations. an E1 ubiquitin-activating enzyme uses energy released by adenosine triphosphate (ATP) hydrolysis to form a covalent bond between a cysteine residue of its active site and the C-terminal glycine of ubiquitin [10,11]. The activated ubiquitin is then transferred onto an E2 ubiquitin-conjugating enzyme, which itself can bind to one of several E3 ubiquitin ligases. In the final step, E3 ubiquitin ligases mediate the transfer of ubiquitin to a lysine Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. residue of target substrates [12] (Figure1). Less frequently, ubiquitylation occurs on other This article is an open access article acceptors sites including cysteine, threonine and serine residues as well as N-terminal distributed under the terms and methionine [12–15]. Remarkably, ubiquitin itself may be also subjected to ubiquitylation conditions of the Creative Commons at either one of its seven lysine (K) residues (K6, K11, K27, K29, K33, K48 and K63) or its Attribution (CC BY) license (https:// N-terminal methionine (M1—known as linear polyubiquitylation), thereby triggering the creativecommons.org/licenses/by/ formation of poly-ubiquitin chains [16,17]. Depending on the K-linkage used for ubiqui- 4.0/). tylation, these poly-ubiquitin chains may decide different possible fates for the attached J. Clin. Med. 2021, 10, 1783. https://doi.org/10.3390/jcm10081783 https://www.mdpi.com/journal/jcm J. Clin. Med. 2021, 10, x FOR PEER REVIEW 2 of 19 J. Clin. Med. 2021, 10, 1783 2 of 19 formation of poly-ubiquitin chains [16,17]. Depending on the K-linkage used for ubiq- uitylation, these poly-ubiquitin chains may decide different possible fates for the attached proteinprotein [18]. [18]. Among thesethese ubiquitylationubiquitylation types, types, K48-linked K48-linked poly-ubiquitin poly-ubiquitin chains chains represent repre- sentcanonical canonical signals signals for proteasome-mediatedfor proteasome-mediat degradationed degradation [17, 19[17,19],], while while K63-linked K63-linked and andlinear linear (M1) (M1) polyubiquitylation polyubiquitylation may supportmay support non-proteolytic non-proteolytic roles such roles as such signaling as signaling [19–21]. [19–21].Importantly, Importantly, the process the ofprocess ubiquitylation of ubiquity is counteractedlation is counteracted by deubiquitinating by deubiquitinating enzymes enzymes(DUBs) [ 22(DUBs)], whose [22], most whose prominent most prominent families include families the include ubiquitin-specific the ubiquitin-specific proteases (USPs) pro- teasesand the (USPs) otubain and proteases the otubain (OTUs) proteases [23]. (OTUs) [23]. FigureFigure 1. 1. Schematic Schematic representation representation of of ubiqu ubiquitylationitylation and proteasomal protein degradation. ((A)) Proteins Proteins destined destined for for proteasomalproteasomal degradation degradation are are conjugated with ubiquitin in a three-step cascade. First, E1-ubiquitin-activating enzymes bindbind to to ubiquitin in in an ATP-dependent reaction. This This ubiqui ubiquitintin is is transferred transferred onto onto a a E2-ubiquitin E2-ubiquitin conjugating-enzyme. conjugating-enzyme. TheThe E3-ubiquitin-ligase binds binds to to both ubiquitin-conjugated E2-enzymes E2-enzymes and and target target substrates substrates which which thereby thereby undergo modificationmodification with with ubiquitin. ubiquitin. Ubiquitylated Ubiquitylated proteins proteins can can be be po polyubiquitylated.lyubiquitylated. Depicted Depicted is is a a K48 K48 linked linked polyubiquitylation, polyubiquitylation, wherewhere ubiquitin is is consecutively attached attached to to th thee lysine lysine 48 of the already bound ubiquitin. ( (BB)) The The 20S 20S proteasome proteasome core core particleparticle is is made up of α- andand β-subunits. The The assembly assembly to to αββα asymmetricasymmetric heptameric heptameric rings rings is is guided guided by by assembly assembly chaperones. Each 20S core particle consists of two outer α-rings and two inner β-rings. In standard proteasomes (SPs), the chaperones. Each 20S core particle consists of two outer α-rings and two inner β-rings. In standard proteasomes (SPs), the catalytically active subunits are β1, β2 and β5. In immunoproteasomes (IPs), these subunits are replaced by the inducible catalytically active subunits are β1, β2 and β5. In immunoproteasomes (IPs), these subunits are replaced by the inducible subunits LMP2 (β1i), MECL1 (β2i) and LMP7 (β5i). IPs are preferentially incorporated to newly synthetized proteasomes β β β insubunits response LMP2 to IFN, ( 1i), as MECL1 indicated. ( 2i) Additional and LMP7 isotypes ( 5i). IPs include are preferentially the thymoproteasome incorporated (TP) to newly which synthetized contains a proteasomes unique β5t proteasein response subunit to IFN, and as the indicated. spermatoproteasome Additional isotypes(SpP) that include incorporates the thymoproteasome a specific structural (TP) α4s which subunit. contains The active a unique sitesβ of5t theprotease catalytic subunit subunits and theface spermatoproteasome the inside of the 20S (SpP)barrelthat shape. incorporates Proteasomes a specific can bind structural to differentα4s subunit.regulators The on active one or sites both of sides.the catalytic The 19S subunits regulator face has the receptors inside of for the poly-ubiquitylated 20S barrel shape. proteins Proteasomes and helps can bind to unfold to different the proteins, regulators remove on one ubiquitin or both fromsides. substrates The 19S regulator and translocate has receptors them into for the poly-ubiquitylated 20S for degradation. proteins The regulators and helps can to unfold attach theto different proteins, isoforms remove ubiquitinon either orfrom both substrates sides. Additionally, and translocate combin themations into theof the 20S 19S for regulator degradation. and ThePA28 regulatorsαβ/γ or PA200 can attach regulators to different exist. isoforms on either or both sides. Additionally, combinations of the 19S regulator and PA28αβ/γ or PA200 regulators exist. As alluded earlier, K48-linked ubiquitination is a prerequisite for the breakdown of intracellularAs alluded proteins earlier, by K48-linked26S proteasome ubiquitination complexes, is which a prerequisite themselves for theare
Load more

Recommended publications
  • PSMB5 Antibody Cat
    PSMB5 Antibody Cat. No.: 57-791 PSMB5 Antibody Western blot analysis of PSMB5 using rabbit polyclonal PSMB5 Antibody immunohistochemistry analysis in PSMB5 Antibody using 293 cell lysates (2 ug/lane) either formalin fixed and paraffin embedded human skin tissue nontransfected (Lane 1) or transiently transfected (Lane 2) followed by peroxidase conjugation of the secondary with the PSMB5 gene. antibody and DAB staining. Specifications HOST SPECIES: Rabbit SPECIES REACTIVITY: Human This PSMB5 antibody is generated from rabbits immunized with a KLH conjugated IMMUNOGEN: synthetic peptide between 235-263 amino acids from the C-terminal region of human PSMB5. TESTED APPLICATIONS: IHC-P, WB For WB starting dilution is: 1:1000 APPLICATIONS: For IHC-P starting dilution is: 1:10~50 October 1, 2021 1 https://www.prosci-inc.com/psmb5-antibody-57-791.html PREDICTED MOLECULAR 28 kDa WEIGHT: Properties This antibody is purified through a protein A column, followed by peptide affinity PURIFICATION: purification. CLONALITY: Polyclonal ISOTYPE: Rabbit Ig CONJUGATE: Unconjugated PHYSICAL STATE: Liquid BUFFER: Supplied in PBS with 0.09% (W/V) sodium azide. CONCENTRATION: batch dependent Store at 4˚C for three months and -20˚C, stable for up to one year. As with all antibodies STORAGE CONDITIONS: care should be taken to avoid repeated freeze thaw cycles. Antibodies should not be exposed to prolonged high temperatures. Additional Info OFFICIAL SYMBOL: PSMB5 Proteasome subunit beta type-5, Macropain epsilon chain, Multicatalytic endopeptidase ALTERNATE NAMES: complex epsilon chain, Proteasome chain 6, Proteasome epsilon chain, Proteasome subunit MB1, Proteasome subunit X, PSMB5, LMPX, MB1, X ACCESSION NO.: P28074 PROTEIN GI NO.: 187608890 GENE ID: 5693 USER NOTE: Optimal dilutions for each application to be determined by the researcher.
    [Show full text]
  • 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).
    [Show full text]
  • 32-2748: PSMB1 Recombinant Protein Description Product Info
    9853 Pacific Heights Blvd. Suite D. San Diego, CA 92121, USA Tel: 858-263-4982 Email: [email protected] 32-2748: PSMB1 Recombinant Protein Alternative HC5,PSC5,PMSB1,FLJ25321,KIAA1838,PSMB1,Proteasome subunit beta type-1,Proteasome component Name : C5,Macropain subunit C5,Multicatalytic endopeptidase complex subunit C5,Proteasome gamma chain. Description Source : Escherichia Coli. PSMB1 Human Recombinant fused to 37 amino acid His Tag at N-terminal produced in E.Coli is a single, non-glycosylated, polypeptide chain containing 250 amino acids (30-241) and having a molecular mass of 27.7 kDa. The PSMB1 is purified by proprietary chromatographic techniques. PSMB1 is part of the proteasome B-type family, also identified as the T1B family, that is a 20S core beta subunit. PSMB1 is tightly linked to the TBP (TATA-binding protein) gene in human and in mouse, and is transcribed in the opposite orientation in both species.The main function of PSMB1 is its degradation activity of unnecessary or damaged proteins by proteolysis. PSMB1 is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with arg, phe, tyr, leu, and glu adjacent to the leaving group at neutral or slightly basic ph. the proteasome has an atp-dependent proteolytic activity. Product Info Amount : 10 µg Purification : Greater than 95.0% as determined by SDS-PAGE. Content : The PSMB1 solution contains 20mM Tris-HCl pH-8, 1mM DTT and 10% glycerol. PSMB1 Recombinant Human although stable at 4°C for 30 days, should be stored desiccated Storage condition : below -20°C for periods greater than 30 days.
    [Show full text]
  • View of HER2: Human Epidermal Growth Factor Receptor 2; TNBC: Triple-Negative Breast Resistance to Systemic Therapy in Patients with Breast Cancer
    Wen et al. Cancer Cell Int (2018) 18:128 https://doi.org/10.1186/s12935-018-0625-9 Cancer Cell International PRIMARY RESEARCH Open Access Sulbactam‑enhanced cytotoxicity of doxorubicin in breast cancer cells Shao‑hsuan Wen1†, Shey‑chiang Su2†, Bo‑huang Liou3, Cheng‑hao Lin1 and Kuan‑rong Lee1* Abstract Background: Multidrug resistance (MDR) is a major obstacle in breast cancer treatment. The predominant mecha‑ nism underlying MDR is an increase in the activity of adenosine triphosphate (ATP)-dependent drug efux trans‑ porters. Sulbactam, a β-lactamase inhibitor, is generally combined with β-lactam antibiotics for treating bacterial infections. However, sulbactam alone can be used to treat Acinetobacter baumannii infections because it inhibits the expression of ATP-binding cassette (ABC) transporter proteins. This is the frst study to report the efects of sulbactam on mammalian cells. Methods: We used the breast cancer cell lines as a model system to determine whether sulbactam afects cancer cells. The cell viabilities in the present of doxorubicin with or without sulbactam were measured by MTT assay. Protein identities and the changes in protein expression levels in the cells after sulbactam and doxorubicin treatment were determined using LC–MS/MS. Real-time reverse transcription polymerase chain reaction (real-time RT-PCR) was used to analyze the change in mRNA expression levels of ABC transporters after treatment of doxorubicin with or without sulbactam. The efux of doxorubicin was measures by the doxorubicin efux assay. Results: MTT assay revealed that sulbactam enhanced the cytotoxicity of doxorubicin in breast cancer cells. The results of proteomics showed that ABC transporter proteins and proteins associated with the process of transcription and initiation of translation were reduced.
    [Show full text]
  • 20S Proteasome Α3 (Phospho Ser250) Polyclonal Antibody Catalog # AP67328
    10320 Camino Santa Fe, Suite G San Diego, CA 92121 Tel: 858.875.1900 Fax: 858.622.0609 20S Proteasome α3 (phospho Ser250) Polyclonal Antibody Catalog # AP67328 Specification 20S Proteasome α3 (phospho Ser250) Polyclonal Antibody - Product Information Application WB Primary Accession P25788 Reactivity Human, Mouse, Rat Host Rabbit Clonality Polyclonal 20S Proteasome α3 (phospho Ser250) Polyclonal Antibody - Additional Information Gene ID 5684 Other Names PSMA3; HC8; PSC8; Proteasome subunit alpha type-3; Macropain subunit C8; Multicatalytic endopeptidase complex subunit C8; Proteasome component C8 Dilution WB~~Western Blot: 1/500 - 1/2000. Immunohistochemistry: 1/100 - 1/300. ELISA: 1/10000. Not yet tested in other applications. Format Liquid in PBS containing 50% glycerol, 0.5% BSA and 0.02% sodium azide. Storage Conditions -20℃ 20S Proteasome α3 (phospho Ser250) Polyclonal Antibody - Protein Information Name PSMA3 Synonyms HC8, PSC8 Function Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with Page 1/2 10320 Camino Santa Fe, Suite G San Diego, CA 92121 Tel: 858.875.1900 Fax: 858.622.0609 different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP- dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin- independent protein degradation. This type of proteolysis is required in several 20S Proteasome α3 (phospho Ser250) pathways including spermatogenesis Polyclonal Antibody - Background (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic Component of the 20S core proteasome peptides (20S-PA28 complex).
    [Show full text]
  • On the Role of the Immunoproteasome in Transplant Rejection
    Immunogenetics (2019) 71:263–271 https://doi.org/10.1007/s00251-018-1084-0 REVIEW On the role of the immunoproteasome in transplant rejection Michael Basler1,2 & Jun Li1,3 & Marcus Groettrup1,2 Received: 17 July 2018 /Accepted: 4 September 2018 /Published online: 15 September 2018 # Springer-Verlag GmbH Germany, part of Springer Nature 2018 Abstract The immunoproteasome is expressed in cells of hematopoietic origin and is induced during inflammation by IFN-γ. Targeting the immunoproteasome with selective inhibitors has been shown to be therapeutically effective in pre-clinical models for autoim- mune diseases, colitis-associated cancer formation, and transplantation. Immunoproteasome inhibition prevents activation and proliferation of lymphocytes, lowers MHC class I cell surface expression, reduces the expression of cytokines of activated immune cells, and curtails T helper 1 and 17 cell differentiation. This might explain the in vivo efficacy of immunoproteasome inhibition in different pre-clinical disease models for autoimmunity, cancer, and transplantation. In this review, we summarize the effect of immunoproteasome inhibition in different animal models for transplantation. Keywords Proteasome . Immunoproteasome . Antigen processing . Antigen presentation . Transplantation Introduction et al. 2012). Depending on the cell type and the presence or absence of the pro-inflammatory cytokine interferon (IFN)-γ, The proteasome is responsible for the degradation of proteins the three inducible β subunits of the immunoproteasome low in the cytoplasm and nuclei of all eukaryotic cells and exerts molecular mass polypeptide (LMP)2 (β1i), multicatalytic en- numerous essential regulatory functions in nearly all cell bio- dopeptidase complex-like (MECL)-1 (β2i), and LMP7 (β5i), logical pathways. The 26S proteasome degrades poly- can, in addition to the corresponding constitutive subunits ubiquitylated protein substrates and consists of a 19S regulator β1c, β2c, and β5c, enrich the cellular assortment of catalyti- and a 20S proteolytic core complex.
    [Show full text]
  • Inhibition of the Nrf2 Transcription Factor by the Alkaloid
    Oncogene (2013) 32, 4825–4835 & 2013 Macmillan Publishers Limited All rights reserved 0950-9232/13 www.nature.com/onc ORIGINAL ARTICLE Inhibition of the Nrf2 transcription factor by the alkaloid trigonelline renders pancreatic cancer cells more susceptible to apoptosis through decreased proteasomal gene expression and proteasome activity A Arlt1,4, S Sebens2,4, S Krebs1, C Geismann1, M Grossmann1, M-L Kruse1, S Schreiber1,3 and H Scha¨fer1 Evidence accumulates that the transcription factor nuclear factor E2-related factor 2 (Nrf2) has an essential role in cancer development and chemoresistance, thus pointing to its potential as an anticancer target and undermining its suitability in chemoprevention. Through the induction of cytoprotective and proteasomal genes, Nrf2 confers apoptosis protection in tumor cells, and inhibiting Nrf2 would therefore be an efficient strategy in anticancer therapy. In the present study, pancreatic carcinoma cell lines (Panc1, Colo357 and MiaPaca2) and H6c7 pancreatic duct cells were analyzed for the Nrf2-inhibitory effect of the coffee alkaloid trigonelline (trig), as well as for its impact on Nrf2-dependent proteasome activity and resistance to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and anticancer drug-induced apoptosis. Chemoresistant Panc1 and Colo357 cells exhibit high constitutive Nrf2 activity, whereas chemosensitive MiaPaca2 and H6c7 cells display little basal but strong tert-butylhydroquinone (tBHQ)-inducible Nrf2 activity and drug resistance. Trig efficiently decreased basal and tBHQ-induced Nrf2 activity in all cell lines, an effect relying on a reduced nuclear accumulation of the Nrf2 protein. Along with Nrf2 inhibition, trig blocked the Nrf2-dependent expression of proteasomal genes (for example, s5a/psmd4 and a5/psma5) and reduced proteasome activity in all cell lines tested.
    [Show full text]
  • Analysis of the Stability of 70 Housekeeping Genes During Ips Reprogramming Yulia Panina1,2*, Arno Germond1 & Tomonobu M
    www.nature.com/scientificreports OPEN Analysis of the stability of 70 housekeeping genes during iPS reprogramming Yulia Panina1,2*, Arno Germond1 & Tomonobu M. Watanabe1 Studies on induced pluripotent stem (iPS) cells highly rely on the investigation of their gene expression which requires normalization by housekeeping genes. Whether the housekeeping genes are stable during the iPS reprogramming, a transition of cell state known to be associated with profound changes, has been overlooked. In this study we analyzed the expression patterns of the most comprehensive list to date of housekeeping genes during iPS reprogramming of a mouse neural stem cell line N31. Our results show that housekeeping genes’ expression fuctuates signifcantly during the iPS reprogramming. Clustering analysis shows that ribosomal genes’ expression is rising, while the expression of cell-specifc genes, such as vimentin (Vim) or elastin (Eln), is decreasing. To ensure the robustness of the obtained data, we performed a correlative analysis of the genes. Overall, all 70 genes analyzed changed the expression more than two-fold during the reprogramming. The scale of this analysis, that takes into account 70 previously known and newly suggested genes, allowed us to choose the most stable of all genes. We highlight the fact of fuctuation of housekeeping genes during iPS reprogramming, and propose that, to ensure robustness of qPCR experiments in iPS cells, housekeeping genes should be used together in combination, and with a prior testing in a specifc line used in each study. We suggest that the longest splice variants of Rpl13a, Rplp1 and Rps18 can be used as a starting point for such initial testing as the most stable candidates.
    [Show full text]
  • King's Research Portal
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by King's Research Portal King’s Research Portal DOI: 10.1016/j.biotechadv.2017.05.004 Document Version Publisher's PDF, also known as Version of record Link to publication record in King's Research Portal Citation for published version (APA): Neville, J. J., Orlando, J., Mann, K., McCloskey, B., & Antoniou, M. N. (2017). Ubiquitous Chromatin-opening Elements (UCOEs): Applications in biomanufacturing and gene therapy. BIOTECHNOLOGY ADVANCES, 557- 564. DOI: 10.1016/j.biotechadv.2017.05.004 Citing this paper Please note that where the full-text provided on King's Research Portal is the Author Accepted Manuscript or Post-Print version this may differ from the final Published version. If citing, it is advised that you check and use the publisher's definitive version for pagination, volume/issue, and date of publication details. And where the final published version is provided on the Research Portal, if citing you are again advised to check the publisher's website for any subsequent corrections. General rights Copyright and moral rights for the publications made accessible in the Research Portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognize and abide by the legal requirements associated with these rights. •Users may download and print one copy of any publication from the Research Portal for the purpose of private study or research. •You may not further distribute the material or use it for any profit-making activity or commercial gain •You may freely distribute the URL identifying the publication in the Research Portal Take down policy If you believe that this document breaches copyright please contact [email protected] providing details, and we will remove access to the work immediately and investigate your claim.
    [Show full text]
  • Proteasome 26S Subunit, Non Atpase 7 (PSMD7)
    RPG282Hu01 10µg Recombinant Proteasome 26S Subunit, Non ATPase 7 (PSMD7) Organism Species: Homo sapiens (Human) Instruction manual FOR IN VITRO USE AND RESEARCH USE ONLY NOT FOR USE IN CLINICAL DIAGNOSTIC PROCEDURES 10th Edition (Revised in Jan, 2014) [ PROPERTIES ] Residues: Met1~Lys324 Tags: Two N-terminal Tags, His-tag and T7-tag Accession: P51665 Host: E. coli Purity: >90% Endotoxin Level: <1.0EU per 1μg (determined by the LAL method). Formulation: Supplied as lyophilized form in 20mM Tris, 150mM NaCl, pH8.0, containing 1mM EDTA, 1mM DTT, 0.01% sarcosyl, 5% trehalose, and preservative. Predicted isoelectric point: 6.7 Predicted Molecular Mass: 40.8kDa Applications: SDS-PAGE; WB; ELISA; IP. (May be suitable for use in other assays to be determined by the end user.) [ USAGE ] Reconstitute in sterile ddH2O. [ STORAGE AND STABILITY ] Storage: Avoid repeated freeze/thaw cycles. Store at 2-8oC for one month. Aliquot and store at -80oC for 12 months. Stability Test: The thermal stability is described by the loss rate of the target protein. The loss rate was determined by accelerated thermal degradation test, that is, incubate the protein at 37oC for 48h, and no obvious degradation and precipitation were observed. (Referring from China Biological Products Standard, which was calculated by the Arrhenius equation.) The loss of this protein is less than 5% within the expiration date under appropriate storage condition. [ SEQUENCES ] The sequence of the target protein is listed below. MPELAVQKVV VHPLVLLSVV DHFNRIGKVG NQKRVVGVLL GSWQKKVLDV SNSFAVPFDE DDKDDSVWFL DHDYLENMYG MFKKVNARER IVGWYHTGPK LHKNDIAINE LMKRYCPNSV LVIIDVKPKD LGLPTEAYIS VEEVHDDGTP TSKTFEHVTS EIGAEEAEEV GVEHLLRDIK DTTVGTLSQR ITNQVHGLKG LNSKLLDIRS YLEKVATGKL PINHQIIYQL QDVFNLLPDV SLQEFVKAFY LKTNDQMVVV YLASLIRSVV ALHNLINNKI ANRDAEKKEG QEKEESKKDR KEDKEKDKDK EKSDVKKEEK KEKK [ REFERENCES ] 1.
    [Show full text]
  • Snps) Distant from Xenobiotic Response Elements Can Modulate Aryl Hydrocarbon Receptor Function: SNP-Dependent CYP1A1 Induction S
    Supplemental material to this article can be found at: http://dmd.aspetjournals.org/content/suppl/2018/07/06/dmd.118.082164.DC1 1521-009X/46/9/1372–1381$35.00 https://doi.org/10.1124/dmd.118.082164 DRUG METABOLISM AND DISPOSITION Drug Metab Dispos 46:1372–1381, September 2018 Copyright ª 2018 by The American Society for Pharmacology and Experimental Therapeutics Single Nucleotide Polymorphisms (SNPs) Distant from Xenobiotic Response Elements Can Modulate Aryl Hydrocarbon Receptor Function: SNP-Dependent CYP1A1 Induction s Duan Liu, Sisi Qin, Balmiki Ray,1 Krishna R. Kalari, Liewei Wang, and Richard M. Weinshilboum Division of Clinical Pharmacology, Department of Molecular Pharmacology and Experimental Therapeutics (D.L., S.Q., B.R., L.W., R.M.W.) and Division of Biomedical Statistics and Informatics, Department of Health Sciences Research (K.R.K.), Mayo Clinic, Rochester, Minnesota Received April 22, 2018; accepted June 28, 2018 ABSTRACT Downloaded from CYP1A1 expression can be upregulated by the ligand-activated aryl fashion. LCLs with the AA genotype displayed significantly higher hydrocarbon receptor (AHR). Based on prior observations with AHR-XRE binding and CYP1A1 mRNA expression after 3MC estrogen receptors and estrogen response elements, we tested treatment than did those with the GG genotype. Electrophoretic the hypothesis that single-nucleotide polymorphisms (SNPs) map- mobility shift assay (EMSA) showed that oligonucleotides with the ping hundreds of base pairs (bp) from xenobiotic response elements AA genotype displayed higher LCL nuclear extract binding after (XREs) might influence AHR binding and subsequent gene expres- 3MC treatment than did those with the GG genotype, and mass dmd.aspetjournals.org sion.
    [Show full text]
  • Role of Phytochemicals in Colon Cancer Prevention: a Nutrigenomics Approach
    Role of phytochemicals in colon cancer prevention: a nutrigenomics approach Marjan J van Erk Promotor: Prof. Dr. P.J. van Bladeren Hoogleraar in de Toxicokinetiek en Biotransformatie Wageningen Universiteit Co-promotoren: Dr. Ir. J.M.M.J.G. Aarts Universitair Docent, Sectie Toxicologie Wageningen Universiteit Dr. Ir. B. van Ommen Senior Research Fellow Nutritional Systems Biology TNO Voeding, Zeist Promotiecommissie: Prof. Dr. P. Dolara University of Florence, Italy Prof. Dr. J.A.M. Leunissen Wageningen Universiteit Prof. Dr. J.C. Mathers University of Newcastle, United Kingdom Prof. Dr. M. Müller Wageningen Universiteit Dit onderzoek is uitgevoerd binnen de onderzoekschool VLAG Role of phytochemicals in colon cancer prevention: a nutrigenomics approach Marjan Jolanda van Erk Proefschrift ter verkrijging van graad van doctor op gezag van de rector magnificus van Wageningen Universiteit, Prof.Dr.Ir. L. Speelman, in het openbaar te verdedigen op vrijdag 1 oktober 2004 des namiddags te vier uur in de Aula Title Role of phytochemicals in colon cancer prevention: a nutrigenomics approach Author Marjan Jolanda van Erk Thesis Wageningen University, Wageningen, the Netherlands (2004) with abstract, with references, with summary in Dutch ISBN 90-8504-085-X ABSTRACT Role of phytochemicals in colon cancer prevention: a nutrigenomics approach Specific food compounds, especially from fruits and vegetables, may protect against development of colon cancer. In this thesis effects and mechanisms of various phytochemicals in relation to colon cancer prevention were studied through application of large-scale gene expression profiling. Expression measurement of thousands of genes can yield a more complete and in-depth insight into the mode of action of the compounds.
    [Show full text]