Huntington's Disease Products
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
An Overview of the Role of Hdacs in Cancer Immunotherapy
International Journal of Molecular Sciences Review Immunoepigenetics Combination Therapies: An Overview of the Role of HDACs in Cancer Immunotherapy Debarati Banik, Sara Moufarrij and Alejandro Villagra * Department of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, The George Washington University, 800 22nd St NW, Suite 8880, Washington, DC 20052, USA; [email protected] (D.B.); [email protected] (S.M.) * Correspondence: [email protected]; Tel.: +(202)-994-9547 Received: 22 March 2019; Accepted: 28 April 2019; Published: 7 May 2019 Abstract: Long-standing efforts to identify the multifaceted roles of histone deacetylase inhibitors (HDACis) have positioned these agents as promising drug candidates in combatting cancer, autoimmune, neurodegenerative, and infectious diseases. The same has also encouraged the evaluation of multiple HDACi candidates in preclinical studies in cancer and other diseases as well as the FDA-approval towards clinical use for specific agents. In this review, we have discussed how the efficacy of immunotherapy can be leveraged by combining it with HDACis. We have also included a brief overview of the classification of HDACis as well as their various roles in physiological and pathophysiological scenarios to target key cellular processes promoting the initiation, establishment, and progression of cancer. Given the critical role of the tumor microenvironment (TME) towards the outcome of anticancer therapies, we have also discussed the effect of HDACis on different components of the TME. We then have gradually progressed into examples of specific pan-HDACis, class I HDACi, and selective HDACis that either have been incorporated into clinical trials or show promising preclinical effects for future consideration. -
Table 2. Significant
Table 2. Significant (Q < 0.05 and |d | > 0.5) transcripts from the meta-analysis Gene Chr Mb Gene Name Affy ProbeSet cDNA_IDs d HAP/LAP d HAP/LAP d d IS Average d Ztest P values Q-value Symbol ID (study #5) 1 2 STS B2m 2 122 beta-2 microglobulin 1452428_a_at AI848245 1.75334941 4 3.2 4 3.2316485 1.07398E-09 5.69E-08 Man2b1 8 84.4 mannosidase 2, alpha B1 1416340_a_at H4049B01 3.75722111 3.87309653 2.1 1.6 2.84852656 5.32443E-07 1.58E-05 1110032A03Rik 9 50.9 RIKEN cDNA 1110032A03 gene 1417211_a_at H4035E05 4 1.66015788 4 1.7 2.82772795 2.94266E-05 0.000527 NA 9 48.5 --- 1456111_at 3.43701477 1.85785922 4 2 2.8237185 9.97969E-08 3.48E-06 Scn4b 9 45.3 Sodium channel, type IV, beta 1434008_at AI844796 3.79536664 1.63774235 3.3 2.3 2.75319499 1.48057E-08 6.21E-07 polypeptide Gadd45gip1 8 84.1 RIKEN cDNA 2310040G17 gene 1417619_at 4 3.38875643 1.4 2 2.69163229 8.84279E-06 0.0001904 BC056474 15 12.1 Mus musculus cDNA clone 1424117_at H3030A06 3.95752801 2.42838452 1.9 2.2 2.62132809 1.3344E-08 5.66E-07 MGC:67360 IMAGE:6823629, complete cds NA 4 153 guanine nucleotide binding protein, 1454696_at -3.46081884 -4 -1.3 -1.6 -2.6026947 8.58458E-05 0.0012617 beta 1 Gnb1 4 153 guanine nucleotide binding protein, 1417432_a_at H3094D02 -3.13334396 -4 -1.6 -1.7 -2.5946297 1.04542E-05 0.0002202 beta 1 Gadd45gip1 8 84.1 RAD23a homolog (S. -
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. -
Protein UBE2R2
Catalogue # Aliquot Size U235-30H-20 20 µg U235-30H-50 50 µg UBE2R2 (UBC3B) Protein Recombinant protein expressed in E.coli cells Catalog # U235-30H Lot # J617 -4 Product Description Purity Recombinant human UBE2R2 (UBC3B) (2-end) was expressed in E. coli cells using an N-terminal His tag. The gene accession number is NM_017811 . The purity of UBE2R2 (UBC3B) was Gene Aliases determined to be >90% by densitometry. CDC34B; E2-CDC34B; UBC3B Approx. MW 32 kDa . Formulation Recombinant protein stored in 50mM sodium phosphate, pH 7.0, 300mM NaCl, 150mM imidazole, 0.1mM PMSF, 0.25mM DTT, 25% glycerol. Storage and Stability o Store product at –70 C. For optimal storage, aliquot target into smaller quantities after centrifugation and store at recommended temperature. For most favorable performance, avoid repeated handling and multiple freeze/thaw cycles. Scientific Background UBE2R2 (UBC3B) or ubiquitin-conjugating enzyme E2R 2 encodes a protein similar to the E2 ubiquitin conjugating enzyme UBC3/CDC34. CK2-dependent phosphorylation of this ubiquitin-conjugating enzyme functions by regulating beta-TrCP substrate recognition and induces UBE2R2 (UBC3B) Protein its interaction with beta-TrCP therby enhancing beta- Recombinant protein expressed in E. coli cells catenin degradation. CK2-dependent phosphorylation of CDC34 and UBC3B functions by regulating BTRC substrate Catalog Number U235-30H recognition (1). UBE2R2 complements a yeast cdc34 Specific Lot Number J617-4 temperature-sensitive mutant. Deletion and site-directed Purity >90% mutagenesis demonstrated that CK2 phosphorylated Concentration 0.1 µg/ µl Stability 1yr at –70 oC from date of shipment UBE2R2 in the C-terminal domain at serine-233; Storage & Shipping Store product at –70 oC. -
Determining HDAC8 Substrate Specificity by Noah Ariel Wolfson A
Determining HDAC8 substrate specificity by Noah Ariel Wolfson A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy (Biological Chemistry) in the University of Michigan 2014 Doctoral Committee: Professor Carol A. Fierke, Chair Professor Robert S. Fuller Professor Anna K. Mapp Associate Professor Patrick J. O’Brien Associate Professor Raymond C. Trievel Dedication My thesis is dedicated to all my family, mentors, and friends who made getting to this point possible. ii Table of Contents Dedication ....................................................................................................................................... ii List of Figures .............................................................................................................................. viii List of Tables .................................................................................................................................. x List of Appendices ......................................................................................................................... xi Abstract ......................................................................................................................................... xii Chapter 1 HDAC8 substrates: Histones and beyond ...................................................................... 1 Overview ..................................................................................................................................... 1 HDAC introduction -
Supplementary Table S4. FGA Co-Expressed Gene List in LUAD
Supplementary Table S4. FGA co-expressed gene list in LUAD tumors Symbol R Locus Description FGG 0.919 4q28 fibrinogen gamma chain FGL1 0.635 8p22 fibrinogen-like 1 SLC7A2 0.536 8p22 solute carrier family 7 (cationic amino acid transporter, y+ system), member 2 DUSP4 0.521 8p12-p11 dual specificity phosphatase 4 HAL 0.51 12q22-q24.1histidine ammonia-lyase PDE4D 0.499 5q12 phosphodiesterase 4D, cAMP-specific FURIN 0.497 15q26.1 furin (paired basic amino acid cleaving enzyme) CPS1 0.49 2q35 carbamoyl-phosphate synthase 1, mitochondrial TESC 0.478 12q24.22 tescalcin INHA 0.465 2q35 inhibin, alpha S100P 0.461 4p16 S100 calcium binding protein P VPS37A 0.447 8p22 vacuolar protein sorting 37 homolog A (S. cerevisiae) SLC16A14 0.447 2q36.3 solute carrier family 16, member 14 PPARGC1A 0.443 4p15.1 peroxisome proliferator-activated receptor gamma, coactivator 1 alpha SIK1 0.435 21q22.3 salt-inducible kinase 1 IRS2 0.434 13q34 insulin receptor substrate 2 RND1 0.433 12q12 Rho family GTPase 1 HGD 0.433 3q13.33 homogentisate 1,2-dioxygenase PTP4A1 0.432 6q12 protein tyrosine phosphatase type IVA, member 1 C8orf4 0.428 8p11.2 chromosome 8 open reading frame 4 DDC 0.427 7p12.2 dopa decarboxylase (aromatic L-amino acid decarboxylase) TACC2 0.427 10q26 transforming, acidic coiled-coil containing protein 2 MUC13 0.422 3q21.2 mucin 13, cell surface associated C5 0.412 9q33-q34 complement component 5 NR4A2 0.412 2q22-q23 nuclear receptor subfamily 4, group A, member 2 EYS 0.411 6q12 eyes shut homolog (Drosophila) GPX2 0.406 14q24.1 glutathione peroxidase -
Molecular Interactions Underpinning the Phenotype of Hibernation in Mammals Matthew T
© 2019. Published by The Company of Biologists Ltd | Journal of Experimental Biology (2019) 222, jeb160606. doi:10.1242/jeb.160606 REVIEW Molecular interactions underpinning the phenotype of hibernation in mammals Matthew T. Andrews* ABSTRACT most mammals. This Review covers recent advances in the Mammals maintain a constant warm body temperature, facilitating a molecular biology of hibernation, with a focus on molecular wide variety of metabolic reactions. Mammals that hibernate have the interactions underpinning the hibernation phenotype. Specific – ability to slow their metabolism, which in turn reduces their body topics include the torpor arousal cycle, the role of small temperature and leads to a state of hypothermic torpor. For this molecules, changes in gene expression, cold-inducible RNA- metabolic rate reduction to occur on a whole-body scale, molecular binding proteins, the somatosensory system and emerging interactions that change the physiology of cells, tissues and organs information on hibernating primates. This new information not are required, resulting in a major departure from normal mammalian only is beginning to explain how natural hibernators survive homeostasis. The aim of this Review is to cover recent advances in the physiological extremes that would be lethal to most mammals, but molecular biology of mammalian hibernation, including the role of also identifies molecular mechanisms that may prove useful to small molecules, seasonal changes in gene expression, cold- human medicine. inducible RNA-binding proteins, -
Supp Table 6.Pdf
Supplementary Table 6. Processes associated to the 2037 SCL candidate target genes ID Symbol Entrez Gene Name Process NM_178114 AMIGO2 adhesion molecule with Ig-like domain 2 adhesion NM_033474 ARVCF armadillo repeat gene deletes in velocardiofacial syndrome adhesion NM_027060 BTBD9 BTB (POZ) domain containing 9 adhesion NM_001039149 CD226 CD226 molecule adhesion NM_010581 CD47 CD47 molecule adhesion NM_023370 CDH23 cadherin-like 23 adhesion NM_207298 CERCAM cerebral endothelial cell adhesion molecule adhesion NM_021719 CLDN15 claudin 15 adhesion NM_009902 CLDN3 claudin 3 adhesion NM_008779 CNTN3 contactin 3 (plasmacytoma associated) adhesion NM_015734 COL5A1 collagen, type V, alpha 1 adhesion NM_007803 CTTN cortactin adhesion NM_009142 CX3CL1 chemokine (C-X3-C motif) ligand 1 adhesion NM_031174 DSCAM Down syndrome cell adhesion molecule adhesion NM_145158 EMILIN2 elastin microfibril interfacer 2 adhesion NM_001081286 FAT1 FAT tumor suppressor homolog 1 (Drosophila) adhesion NM_001080814 FAT3 FAT tumor suppressor homolog 3 (Drosophila) adhesion NM_153795 FERMT3 fermitin family homolog 3 (Drosophila) adhesion NM_010494 ICAM2 intercellular adhesion molecule 2 adhesion NM_023892 ICAM4 (includes EG:3386) intercellular adhesion molecule 4 (Landsteiner-Wiener blood group)adhesion NM_001001979 MEGF10 multiple EGF-like-domains 10 adhesion NM_172522 MEGF11 multiple EGF-like-domains 11 adhesion NM_010739 MUC13 mucin 13, cell surface associated adhesion NM_013610 NINJ1 ninjurin 1 adhesion NM_016718 NINJ2 ninjurin 2 adhesion NM_172932 NLGN3 neuroligin -
The MALDI TOF E2/E3 Ligase Assay As an Universal Tool for Drug Discovery in the Ubiquitin Pathway
bioRxiv preprint doi: https://doi.org/10.1101/224600; this version posted November 29, 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-NC-ND 4.0 International license. The MALDI TOF E2/E3 ligase assay as an universal tool for drug discovery in the ubiquitin pathway Virginia De Cesare*1, Clare Johnson2, Victoria Barlow2, James Hastie2 Axel Knebel1 and 5 Matthias Trost*1,3 1MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Dow St, Dundee, DD1 5EH, Scotland, UK; 2MRC Protein Phosphorylation and Ubiquitylation Unit Reagents and Services, University of Dundee, Dow St, Dundee, DD1 5EH, Scotland, UK; . 3Institute for Cell and Molecular Biosciences, Newcastle University, Framlington Place, Newcastle-upon-Tyne, 10 NE2 1HH, UK *To whom correspondence should be addressed: Virginia De Cesare ([email protected]) Matthias Trost ([email protected]) 15 Contact information: V.D.C.: MRC PPU, University of Dundee, Dow St, Dundee, DD1 5EH, Phone: +44 1382 20 85822 M.T.: Newcastle University, Institute for Cell and Molecular Biosciences, Framlington Place, Newcastle-upon-Tyne, NE2 4HH, Phone: +44 191 2087009 Key words: Ubiquitin, E3 ligase, E2 enzyme, MALDI TOF, mass spectrometry, drug 25 discovery, high-throughput, assay, MDM2, HOIP, ITCH 1 bioRxiv preprint doi: https://doi.org/10.1101/224600; this version posted November 29, 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. -
Structure and Function of Metallohydrolases in the Arginase- Deacetylase Family
University of Pennsylvania ScholarlyCommons Publicly Accessible Penn Dissertations 2016 Structure and Function of Metallohydrolases in the Arginase- Deacetylase Family Yang Hai University of Pennsylvania, [email protected] Follow this and additional works at: https://repository.upenn.edu/edissertations Part of the Biochemistry Commons Recommended Citation Hai, Yang, "Structure and Function of Metallohydrolases in the Arginase-Deacetylase Family" (2016). Publicly Accessible Penn Dissertations. 1753. https://repository.upenn.edu/edissertations/1753 This paper is posted at ScholarlyCommons. https://repository.upenn.edu/edissertations/1753 For more information, please contact [email protected]. Structure and Function of Metallohydrolases in the Arginase-Deacetylase Family Abstract Arginases and deacetylases are metallohydrolases that catalyze two distinct chemical transformations. The arginases catalyze the hydrolysis of the guanidinium group of arginine by using a hydroxide ion 2+ 2+ bridging the binuclear manganese cluster (Mn A-Mn B) for nucleophilic attack. The deacetylases catalyze the hydrolysis of amide bonds by using a mononuclear Zn2+-ion activated water molecule as the nucleophile. Despite the diverse functions, metallohydrolases of the arginase-deacetylase superfamily 2+ share the same characteristic α/β hydrolase core fold and a conserved metal binding site (the Mn B site in arginase corresponds to the catalytic Zn2+ site in deacetylase) which is essential for catalysis in both enzymes. We report crystal structure of formiminoglutamase from the parasitic protozoan Trypanosoma cruzi and confirm that formiminoglutamase is a Mn2+-requiring hydrolase that belongs to the arginase- deacetylase superfamily. We also report the crystal structure of an arginase-like protein from Trypanosoma brucei (TbARG) with unknown function. Although its biological role remains enigmatic, the 2+ evolutionarily more conserved Mn B site can be readily restored in TbARG through side-directed mutagenesis. -
Comparative Analysis of the Ubiquitin-Proteasome System in Homo Sapiens and Saccharomyces Cerevisiae
Comparative Analysis of the Ubiquitin-proteasome system in Homo sapiens and Saccharomyces cerevisiae Inaugural-Dissertation zur Erlangung des Doktorgrades der Mathematisch-Naturwissenschaftlichen Fakultät der Universität zu Köln vorgelegt von Hartmut Scheel aus Rheinbach Köln, 2005 Berichterstatter: Prof. Dr. R. Jürgen Dohmen Prof. Dr. Thomas Langer Dr. Kay Hofmann Tag der mündlichen Prüfung: 18.07.2005 Zusammenfassung I Zusammenfassung Das Ubiquitin-Proteasom System (UPS) stellt den wichtigsten Abbauweg für intrazelluläre Proteine in eukaryotischen Zellen dar. Das abzubauende Protein wird zunächst über eine Enzym-Kaskade mit einer kovalent gebundenen Ubiquitinkette markiert. Anschließend wird das konjugierte Substrat vom Proteasom erkannt und proteolytisch gespalten. Ubiquitin besitzt eine Reihe von Homologen, die ebenfalls posttranslational an Proteine gekoppelt werden können, wie z.B. SUMO und NEDD8. Die hierbei verwendeten Aktivierungs- und Konjugations-Kaskaden sind vollständig analog zu der des Ubiquitin- Systems. Es ist charakteristisch für das UPS, daß sich die Vielzahl der daran beteiligten Proteine aus nur wenigen Proteinfamilien rekrutiert, die durch gemeinsame, funktionale Homologiedomänen gekennzeichnet sind. Einige dieser funktionalen Domänen sind auch in den Modifikations-Systemen der Ubiquitin-Homologen zu finden, jedoch verfügen diese Systeme zusätzlich über spezifische Domänentypen. Homologiedomänen lassen sich als mathematische Modelle in Form von Domänen- deskriptoren (Profile) beschreiben. Diese Deskriptoren können wiederum dazu verwendet werden, mit Hilfe geeigneter Verfahren eine gegebene Proteinsequenz auf das Vorliegen von entsprechenden Homologiedomänen zu untersuchen. Da die im UPS involvierten Homologie- domänen fast ausschließlich auf dieses System und seine Analoga beschränkt sind, können domänen-spezifische Profile zur Katalogisierung der UPS-relevanten Proteine einer Spezies verwendet werden. Auf dieser Basis können dann die entsprechenden UPS-Repertoires verschiedener Spezies miteinander verglichen werden. -
Continuous Activity Assay for HDAC11 Enabling Reevaluation of HDAC
This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes. Article Cite This: ACS Omega 2019, 4, 19895−19904 http://pubs.acs.org/journal/acsodf Continuous Activity Assay for HDAC11 Enabling Reevaluation of HDAC Inhibitors † † ‡ § † † ⊥ Zsofía Kutil, Jana Mikesovǎ ,́Matthes Zessin, Marat Meleshin, Zora Novaková ,́ Glenda Alquicer, , ∥ ‡ † § Alan Kozikowski, Wolfgang Sippl, Cyril Barinka,̌ *, and Mike Schutkowski*, † Institute of Biotechnology of the Czech Academy of Sciences, BIOCEV, Prumyslova 595, 252 50 Vestec, Czech Republic ‡ Department of Medicinal Chemistry, Institute of Pharmacy, Martin-Luther-University Halle-Wittenberg, 06120 Halle (Saale), Germany § Department of Enzymology, Institute of Biochemistry and Biotechnology, Charles Tanford Protein Centre, Martin Luther University Halle-Wittenberg, Kurt-Mothes-Straße 3a, 06120 Halle (Saale), Germany ∥ StarWise Therapeutics LLC, 505 S Rosa Road, Suite 27, Madison, Wisconsin 53719-1235, United States *S Supporting Information ABSTRACT: Histone deacetylase 11 (HDAC11) preferentially removes fatty acid residues from lysine side chains in a peptide or protein environment. Here, we report the development and validation of a continuous fluorescence-based activity assay using an internally quenched TNFα-derived peptide derivative as a substrate. The threonine residue in the +1 position was replaced by the quencher amino acid 3′-nitro-L-tyrosine and the fatty acyl moiety substituted by 2-aminobenzoylated 11- aminoundecanoic acid. The resulting peptide substrate enables fluorescence-based direct and continuous readout of HDAC11-mediated amide bond cleavage fully compatible with high-throughput screening formats. The Z′-factor is higher than 0.85 for the 15 μM substrate concentration, and the signal-to-noise ratio exceeds 150 for 384-well plates.