DOCSLIB.ORG

(EPITOPES) Stage (I-IV) Clones Description of the Genes That Are In

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
(EPITOPES) Stage (I-IV) Clones Description of the Genes That Are In Table: 1 Description of Stage I-IV clones (EPITOPES) Stage Description of the genes that are in- Size of Unigene # Serex Y/N Region of Antigen expression in any type of cancer (I-IV) frame with T7 10B gene the mRNA similarity clones peptide of AA 1F6 gi|18490914|gb|BC022506.1| 49 AA Hs.9222 N 165-213 Overexpressed in ovarian, nonsmall cell lung Homo sapiens, estrogen receptor carcinoma, pancreatic ductal cacinoma binding site associated,antigen,9 RCAS 2B3 gi|7023439|dbj|AK001891.1|, 10 AA Hs.528654 N 350-360 Not associated with cancer Homo sapiens cDNA FLJ11029 fis, clone PLACE1004156 2B4 gi|22042983|ref|XM_032391.3|, 212 AA Hs.446206 N 258-469 Expression levels are higher in myelogenous leukemia Homo sapiens similar to nuclear and lymphoblastic leukemia cells. autoantigenic sperm protein (histone- binding)(NASP) 2F7 gi|22042983|ref|XM_032391.3|, 15 AA Hs.446206 N 256-270 Expression levels are higher in myelogenous leukemia Homo sapiens similar to Nuclear and lymphoblastic leukemia cells. autoantigenic sperm protein (NASP) 2G4 gi|20987351|gb|BC030160.1| , 148 AA Hs.310621 N 1-148 eIF-5A2 sharing 82% identity of amino acid sequence Homo sapiens, eukaryotic translation with eIF-5A , is a candidate oncogene related to initiation factor 5A development of ovarian cancer. 3A9 gi|4507212|ref|NM_003135.1|, Homo 25 AA Hs.2943 N 119-143 Transcript generated by alternative splicing between sapiens signal recognition particle exon 14 of the Adenomatous polyposis coli gene and 19kDa (SRP19) SRP19 is observed and its expression is higher in Colorectal cancer 3C11 gi|16579884|ref|NM_000968.2| 68 AA Hs.186350 N 360-427 over-expression of L7a and L37 mRNA is confirmed in Homo sapiens ribosomal protein L4 prostate-cancer tissue samples. (RPL4) 4A11 gi|4557446|ref|NM_001270.1|,Homo 86 AA Hs.311553 N 107-192 Not associated with cancer sapiens chromodomain helicase DNA binding protein 1 (CHD1) 4H3 gi|20543465|ref|XM_045343.5|, 92 AA Hs.25812 N 433-524 Three different mutations in Nibrin gene, generating Homo sapiens Nijmegen breakage truncated or aberrant Nibrin transcripts were syndrome 1 (nibrin) observed in different cancer cell lines. 5C3 gi|20987351|gb|BC030160.1|, 118 AA Hs.310621 N 1-118 eIF-5A2 sharing 82% identity of amino acid sequence Homo sapiens, eukaryotic translation with eIF-5A , is a candidate oncogene related to initiation factor 5A development of ovarian cancer. 5C11 gi|535176|emb|X74818.1|HSAHNAKRS, 121 AA Hs.378738 N 393-512 Expression level of AHNAK is higher in melanoma, H.sapiens mRNA of AHNAK-related promyelocytic leukemia HL-60, osteosarcoma. sequence 5F8 gi|7662105|ref|NM_014711.1| , 150 AA Hs.279912 N 434-583 mRNA expression level of another antigen KIAA1416 is Homo sapiens KIAA0419 gene product up-regulated in colon cancer. Table: 2 Description of Stage I-IV clones (MIMOTOPES) Size range of the Mimotopes >=5 amino acids Stag Description of the Peptide sequences Size of Description of Unigene # Serex Region of similarity of AA Antigen expression e genes that are in of Mimotopes, the the sequences Y/N in any type of (I- Mimotope clones in-frame with T7 peptide that Mimotopes mRNA cancer IV) 10 B gene mimic clon es 2B9 gi|28837315|gb|BC0 VIVVLIAVISFPQNYTWL 18 AA gi|20141211|sp Hs.123022 N 172-185 Co-expression of 47588.1| Homo |P18825|A2AC_H Score = 24.8 bits (51), Expect = Beta adrenergic sapiens KIAA1363 UMAN, Alpha- 16 receptor and protein, mRNA 2C-adrenergic Identities = 10/14 (71%), cyclooxgenase 2 in receptor Positives = 10/14 (71%), Gaps = pulmonary (Alpha-2C 3/14 (21%) adenocarcinoma adrenoceptor) Query: 2 IVV--LI-AVISFP 12 (PAC). Beta (Subtype C4) IV LI AVISFP adrenergic Sbjct: 172 IVAVWLISAVISFP 185 receptor may serve as a upstream regulators of aracidonic acid and COX-2 mediated PAC growth. 2D7 gi|14041926|dbj|AK LRGTSGVQPPEIEQ 14 AA gi|32172435|sp Hs.1565 N 514-520 RING protein 027322.1|, Homo |P46934|NED4_H Score = 22.7 bits (46), Expect = Trim32 associated sapiens cDNA UMAN, 70 with skin FLJ14416 fis, Ubiquitin- Identities = 6/7 (85%), carcinogenesis has clone protein ligase Positives = 6/7 (85%) E3-ubiquitin HEMBA1005202, Nedd-4 Query: 8 QPPEIEQ 14 ligase properties highly similar QP EIEQ to SIGNAL Sbjct: 514 QPSEIEQ 520 RECOGNITION PARTICLE 68 KD PROTEIN. 2E7 gi|6330364|dbj|AB0 VLSALPEKNCNTVPFQPP 32 AA gi|34395825|sp Hs.339789 N 167-174 Protein-tyrosine 33020.1|, Homo EDLRYQHCSSRFLE |Q9H106|PTL2_H Score = 24.4 bits (50), Expect = phosphatase ( SAP- sapiens mRNA for UMAN Protein 21 1) is KIAA1194 protein tyrosine Identities = 7/8 (87%), overexpressed in phosphatase Positives = 8/8 (100%) gastrointestinal non-receptor Query: 2 LSALPEKN 9 cancer type substrate LSALPE+N 1-like 2 Sbjct: 167 LSALPERN 174 precursor 2H9 gi|21619682|gb|BC0 ELLRT 5 AA gi|20139301|sp N 407-411 Immunohistochemica 32762.1| , Homo |Q9Y446|PKP3_H Score = 18.9 bits (37), Expect = l localization of sapiens UMAN , 827 plakophilins optineurin, mRNA Plakophilin 3 Identities = 5/5 (100%), (PKP1, PKP2, PKP3, Positives = 5/5 (100%) and p0071) in Query b : 1 ELLRT 5 primary ELLRT oropharyngeal Sbjct c : 407 ELLRT 411 tumors 3B12 gi|21735624|ref|NM GQTSM 5 AA gi|729143|sp|P Hs.370771 N 144-147 mda-6 (p21) may _145690.1| , Homo 38936|CDN1_HUM Score = 16.8 bits (32), Expect = function as a sapiens tyrosine AN , Cyclin- 3595 negative regulator 3monooxygenase/try dependent Identities = 4/4 (100%), of melanoma ptophan 5- kinase Positives = 4/4 (100%) growth, monooxygenase inhibitor 1 Query: 2 QTSM 5 progression and activation (p21) (CDK- QTSM metastasis protein, zeta interacting Sbjct: 144 QTSM 147 polypeptide protein1) (YWHAZ), (Melanoma transcript variant differentiatio 2, mRNA. n associated protein 6 (MDA-6) 5D8 gi|22024583|gb|AC0 KKGPI 5 AA gi|20177863|sp Hs.153714 N 102-106 TNF-alpha 87376.5| , Homo |Q9BXJ2|CQT7_H Score = 18.5 bits (36), Expect = regulates sapiens chromosome UMAN 1109 expression of 11, clone RP11- ,Complement- Identities = 5/5 (100%), downstream 230O19, complete c1q and tumor Positives = 5/5 (100%) components of sequence necrosis Query: 1 KKGPI 5 complement system factor-related KKGPI and plays a role protein 7 Sbjct: 102 KKGPI 106 in energy precursor homeostatis where it is implicated in cachexia, obesity and insulin resistance. 4A4 gi|17028354|gb|BC0 AKVIMR 6 AA gi|5921908|sp| Hs.150595 N 138-142 all-trans-Retinoic 17483.1|BC017483 O43174|CP26_HU Score = 20.6 bits (41), Expect = acid-induced , Homo sapiens, MAN |, 255 expression and clone Cytochrome Identities = 5/5 (100%), regulation of IMAGE:3506553, P450 26 Positives = 5/5 (100%) retinoic acid 4- mRNA. (Retinoic Query: 2 KVIMR 6 hydroxylase acid- KVIMR (CYP26) in human metabolizingcy Sbjct: 138 KVIMR 142 promyelocytic tochrome) leukemia (P450RAI) 5A3 gi|15011541|gb|AF3 YACLKD 6 AA gi|1170473|sp| Hs.433103 N 351-355 CASP-3, CASP-4, 97158.1|AF397158 P42575|ICE2_HU Score = 20.2 bits (40), Expect = CASP-2 , Homo sapiens MAN 342 heterogeneously clone 11 pur ,Caspase-2 Identities = 5/5 (100%), coexpress in alpha-associated precursor Positives = 5/5 (100%) leukemic cell ribosomal RNA (CASP-2) (ICH- Query: 1 YACLK 5 lines gene, 1 protease) YACLK partial sequence Sbjct: 351 YACLK 355 2A3 gi|23271193|gb|BC0 QILFMDP 7 AA gi|729597|sp|P Hs.222405 N 242-246 Ionotropic and 36014.1| , Homo 39086|GLK1_HUM Score = 21.4 bits (43), Expect = metabotropic sapiens poly(A) AN , 142 glutamate receptor polymerase alpha, Glutamate Identities = 5/5 (100%), protein expression mRNA receptor, Positives = 5/5 (100%) in glioneuronal ionotropic Query: 1 QILFM 5 tumors from kainate 1 QILFM patients with precursor Sbjct: 242 QILFM 246 intractable epilepsy 4C10 gi|24756892|gb|AC0 LNTVNTLI 8 AA gi|13633936|sp Hs.416077 N 440-445 Not associated 08507.10| , Homo |Q9NPR2|SM4B_H Score = 21.8 bits (44), Expect = with cancer sapiens chromosome UMAN , 106 19 clone CTC- Semaphorin 4B Identities = 6/6 (100%), 448F2, complete Positives = 6/6 (100%) sequence Query: 1 NTVNTL 6 NTVNTL Sbjct: 440 NTVNTL 445 4D9 gi|21629397|gb|AC0 GNSILLIA 8 AA gi|2842764|sp| Hs.81874 N 3-10 The nuclear 99571.2| , Homo Q99735|GST2_HU Score = 21.4 bits (43), Expect = localisation of sapiens chromosome MAN , 140 GSTpi in tumour 1 clone RP11- Microsomal Identities = 7/8 (87%), cells is a useful 438H8, complete glutathione S- Positives = 7/8 (87%) prognosticator, sequence transferase 2 Query: 1 GNSILLIA 8 and may contribute (Microsomal GNSILL A to the selection GST-2) Sbjct: 3 GNSILLAA 10 of anticancer drugs forgynecological cancers. 2E11 gi|22004067|dbj|AP WDLKSEYS 8 AA gi|1710146|sp| Hs.386726 N 80-85 RGS4 is highly 005356.2| , Homo P49798|RGS4_HU Score = 21.8 bits (44), Expect = expressed in brain sapiens genomic MAN , 106 regions implicated DNA, chromosome Regulator of Identities = 6/6 (100%), in pathophysiology 8q23, clone: G-protein Positives = 6/6 (100%) of scizophrenia KB1198A4, complete signaling 4 Query: 3 LKSEYS 8 sequence. (RGS4) (RGP4) LKSEYS Sbjct: 80 LKSEYS 85 5G9 gi|20072204|gb|BC0 PGCSTTLS 8 AA gi|14423962|sp Hs.255596 N 940-947 Ubiquitin 26241.1| , Homo |O94966|UBPJ_H Score = 18.9 bits (37), Expect = carboxyl-terminal- sapiens ubiquitin- UMAN , 827 hydrolase L1 genes protein isopeptide Ubiquitin Identities = 6/8 (75%), cause autosomal ligase (E3), mRNA carboxyl- Positives = 7/8 (87%) dominant familial terminal Query: 1 PGCSTTLS 8 Parkinson disease. hydrolase 19 PGC+T LS Sbjct: 940 PGCTTLLS 947 4H4 gi|20072204|gb|BC0 PRCSTTLS 8 AA gi|6225843|sp| Hs.128433 N 156-160 Lipocalin-type 26241.1| , Homo O60760|PGD2_HU Score = 18.9 bits (37), Expect = prostaglandin D sapiens ubiquitin- MAN , 827 synthase (L-PGDS) protein isopeptide
Load more

Recommended publications
  • Emerging Roles for 3 Utrs in Neurons
    International Journal of Molecular Sciences Review 0 Emerging Roles for 3 UTRs in Neurons Bongmin Bae and Pedro Miura * Department of Biology, University of Nevada, Reno, NV 89557, USA; [email protected] * Correspondence: [email protected] Received: 8 April 2020; Accepted: 9 May 2020; Published: 12 May 2020 Abstract: The 30 untranslated regions (30 UTRs) of mRNAs serve as hubs for post-transcriptional control as the targets of microRNAs (miRNAs) and RNA-binding proteins (RBPs). Sequences in 30 UTRs confer alterations in mRNA stability, direct mRNA localization to subcellular regions, and impart translational control. Thousands of mRNAs are localized to subcellular compartments in neurons—including axons, dendrites, and synapses—where they are thought to undergo local translation. Despite an established role for 30 UTR sequences in imparting mRNA localization in neurons, the specific RNA sequences and structural features at play remain poorly understood. The nervous system selectively expresses longer 30 UTR isoforms via alternative polyadenylation (APA). The regulation of APA in neurons and the neuronal functions of longer 30 UTR mRNA isoforms are starting to be uncovered. Surprising roles for 30 UTRs are emerging beyond the regulation of protein synthesis and include roles as RBP delivery scaffolds and regulators of alternative splicing. Evidence is also emerging that 30 UTRs can be cleaved, leading to stable, isolated 30 UTR fragments which are of unknown function. Mutations in 30 UTRs are implicated in several neurological disorders—more studies are needed to uncover how these mutations impact gene regulation and what is their relationship to disease severity. Keywords: 30 UTR; alternative polyadenylation; local translation; RNA-binding protein; RNA-sequencing; post-transcriptional regulation 1.
    [Show full text]
  • Therapeutic Strategies in Fragile X Syndrome: Dysregulated Mglur Signaling and Beyond
    Neuropsychopharmacology REVIEWS (2012) 37, 178–195 & 2012 American College of Neuropsychopharmacology All rights reserved 0893-133X/12 ............................................................................................................................................................... REVIEW 178 www.neuropsychopharmacology.org Therapeutic Strategies in Fragile X Syndrome: Dysregulated mGluR Signaling and Beyond 1 ,2 ,1,3 Christina Gross , Elizabeth M Berry-Kravis* and Gary J Bassell* 1 2 Department of Cell Biology, Emory University School of Medicine, Atlanta, GA, USA; Departments of Pediatrics, Neurology, 3 and Biochemistry, Rush University Medical Center, Chicago, IL, USA; Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA Fragile X syndrome (FXS) is an inherited neurodevelopmental disease caused by loss of function of the fragile X mental retardation protein (FMRP). In the absence of FMRP, signaling through group 1 metabotropic glutamate receptors is elevated and insensitive to stimulation, which may underlie many of the neurological and neuropsychiatric features of FXS. Treatment of FXS animal models with negative allosteric modulators of these receptors and preliminary clinical trials in human patients support the hypothesis that metabotropic glutamate receptor signaling is a valuable therapeutic target in FXS. However, recent research has also shown that FMRP may regulate diverse aspects of neuronal signaling downstream of several cell surface receptors, suggesting a possible new route to more direct disease-targeted therapies. Here, we summarize promising recent advances in basic research identifying and testing novel therapeutic strategies in FXS models, and evaluate their potential therapeutic benefits. We provide an overview of recent and ongoing clinical trials motivated by some of these findings, and discuss the challenges for both basic science and clinical applications in the continued development of effective disease mechanism-targeted therapies for FXS.
    [Show full text]
  • Regulators of G-Protein Signaling and Their G Substrates
    0031-6997/11/6303-728–749$25.00 PHARMACOLOGICAL REVIEWS Vol. 63, No. 3 Copyright © 2011 by The American Society for Pharmacology and Experimental Therapeutics 3038/3698761 Pharmacol Rev 63:728–749, 2011 Printed in U.S.A. ASSOCIATE EDITOR: ARTHUR CHRISTOPOULOS Regulators of G-Protein Signaling and Their G␣ Substrates: Promises and Challenges in Their Use as Drug Discovery Targets Adam J. Kimple, Dustin E. Bosch, Patrick M. Gigue`re, and David P. Siderovski Department of Pharmacology, UNC Neuroscience Center, and Lineberger Comprehensive Cancer Center, the University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina Abstract ................................................................................ 728 I. Introduction............................................................................. 729 A. Biological and pharmaceutical importance of G-protein coupled receptor signaling .......... 729 B. The classic guanine nucleotide cycle of heterotrimeric G-protein subunits .................. 729 C. Structural determinants of G-protein subunit function ................................... 730 1. G␣ subunit........................................................................ 730 2. G␤␥ dimer ........................................................................ 730 3. Structural basis for intrinsic GTP hydrolysis activity by G␣ subunits ................... 730 4. Structural features of Regulators of G-protein Signaling—the G␣ GTPase-accelerating proteins..........................................................................
    [Show full text]
  • Methamphetamine-Induced Changes in the Striatal Dopamine Pathway In
    Park et al. Journal of Biomedical Science 2011, 18:83 http://www.jbiomedsci.com/content/18/1/83 RESEARCH Open Access Methamphetamine-induced changes in the striatal dopamine pathway in μ-opioid receptor knockout mice Sang Won Park1*, Xine Shen2, Lu-Tai Tien3, Richard Roman1 and Tangeng Ma1 Abstract Background: Repeated exposure to methamphetamine (METH) can cause not only neurotoxicity but also addiction. Behavioral sensitization is widely used as an animal model for the study of drug addiction. We previously reported that the μ-opioid receptor knockout mice were resistant to METH-induced behavioral sensitization but the mechanism is unknown. Methods: The present study determined whether resistance of the μ-opioid receptor (μ-OR) knockout mice to behavioral sensitization is due to differential expression of the stimulatory G protein a subunit (Gas) or regulators of G-protein signaling (RGS) coupled to the dopamine D1 receptor. Mice received daily intraperitoneal injections of saline or METH (10 mg/kg) for 7 consecutive days to induce sensitization. On day 11(following 4 abstinent days), mice were either given a test dose of METH (10 mg/kg) for behavioral testing or sacrificed for neurochemical assays without additional METH treatment. Results: METH challenge-induced stereotyped behaviors were significantly reduced in the μ-opioid receptor knockout mice when compared with those in wild-type mice. Neurochemical assays indicated that there is a decrease in dopamine D1 receptor ligand binding and an increase in the expression of RGS4 mRNA in the striatum of METH-treated μ-opioid receptor knockout mice but not of METH-treated wild-type mice.
    [Show full text]
  • Supplementary Table 1
    Supplementary Table 1. 492 genes are unique to 0 h post-heat timepoint. The name, p-value, fold change, location and family of each gene are indicated. Genes were filtered for an absolute value log2 ration 1.5 and a significance value of p ≤ 0.05. Symbol p-value Log Gene Name Location Family Ratio ABCA13 1.87E-02 3.292 ATP-binding cassette, sub-family unknown transporter A (ABC1), member 13 ABCB1 1.93E-02 −1.819 ATP-binding cassette, sub-family Plasma transporter B (MDR/TAP), member 1 Membrane ABCC3 2.83E-02 2.016 ATP-binding cassette, sub-family Plasma transporter C (CFTR/MRP), member 3 Membrane ABHD6 7.79E-03 −2.717 abhydrolase domain containing 6 Cytoplasm enzyme ACAT1 4.10E-02 3.009 acetyl-CoA acetyltransferase 1 Cytoplasm enzyme ACBD4 2.66E-03 1.722 acyl-CoA binding domain unknown other containing 4 ACSL5 1.86E-02 −2.876 acyl-CoA synthetase long-chain Cytoplasm enzyme family member 5 ADAM23 3.33E-02 −3.008 ADAM metallopeptidase domain Plasma peptidase 23 Membrane ADAM29 5.58E-03 3.463 ADAM metallopeptidase domain Plasma peptidase 29 Membrane ADAMTS17 2.67E-04 3.051 ADAM metallopeptidase with Extracellular other thrombospondin type 1 motif, 17 Space ADCYAP1R1 1.20E-02 1.848 adenylate cyclase activating Plasma G-protein polypeptide 1 (pituitary) receptor Membrane coupled type I receptor ADH6 (includes 4.02E-02 −1.845 alcohol dehydrogenase 6 (class Cytoplasm enzyme EG:130) V) AHSA2 1.54E-04 −1.6 AHA1, activator of heat shock unknown other 90kDa protein ATPase homolog 2 (yeast) AK5 3.32E-02 1.658 adenylate kinase 5 Cytoplasm kinase AK7
    [Show full text]
  • Suppression of Rgsz1 Function Optimizes the Actions of Opioid
    Suppression of RGSz1 function optimizes the actions PNAS PLUS of opioid analgesics by mechanisms that involve the Wnt/β-catenin pathway Sevasti Gasparia,b,c, Immanuel Purushothamana,b, Valeria Cogliania,b, Farhana Saklotha,b, Rachael L. Neved, David Howlande, Robert H. Ringf, Elliott M. Rossg,h, Li Shena,b, and Venetia Zacharioua,b,1 aFishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029; bFriedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029; cDepartment of Basic Sciences, University of Crete Medical School, 71003 Heraklion, Greece; dGene Delivery Technology Core, Massachusetts General Hospital, MA 01239; eCure Huntington’s Disease Initiative (CHDI) Foundation, Princeton, NJ 08540; fDepartment of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029; gDepartment of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390; and hGreen Center for Systems Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390 Edited by Solomon H. Snyder, Johns Hopkins University School of Medicine, Baltimore, MD, and approved January 5, 2018 (received for review June 23, 2017) Regulator of G protein signaling z1 (RGSz1), a member of the RGS studies have documented brain region-specific effects of other family of proteins, is present in several networks expressing mu RGS proteins (RGS9-2, RGS7, and RGS4) (29–33) on the opioid receptors (MOPRs). By using genetic mouse models for global functional responses of MOPRs, the role of RGSz1 in opioid or brain region-targeted manipulations of RGSz1 expression, we actions is not known. We hypothesized that the expression and demonstrated that the suppression of RGSz1 function increases the activity of RGSz1 are altered by chronic opioid use and that the analgesic efficacy of MOPR agonists in male and female mice and manipulation of RGSz1 expression will impact the development delays the development of morphine tolerance while decreasing the of tolerance to the drug and its analgesic and rewarding effects.
    [Show full text]
  • CHIP Phosphorylation by Protein Kinase G Enhances Protein Quality Control and Attenuates Cardiac Ischemic Injury
    ARTICLE https://doi.org/10.1038/s41467-020-18980-x OPEN CHIP phosphorylation by protein kinase G enhances protein quality control and attenuates cardiac ischemic injury Mark J. Ranek1, Christian Oeing1, Rebekah Sanchez-Hodge3, Kristen M. Kokkonen-Simon 1, Danielle Dillard1, M. Imran Aslam1, Peter P. Rainer 1,6, Sumita Mishra1, Brittany Dunkerly-Eyring1, Ronald J. Holewinski2, Cornelia Virus3, Huaqun Zhang5, Matthew M. Mannion5, Vineet Agrawal1, Virginia Hahn1, Dong I. Lee1, Masayuki Sasaki1, Jennifer E. Van Eyk 2, Monte S. Willis3, Richard C. Page 5, Jonathan C. Schisler 3,4 & ✉ David A. Kass 1 1234567890():,; Proteotoxicity from insufficient clearance of misfolded/damaged proteins underlies many diseases. Carboxyl terminus of Hsc70-interacting protein (CHIP) is an important regulator of proteostasis in many cells, having E3-ligase and chaperone functions and often directing damaged proteins towards proteasome recycling. While enhancing CHIP functionality has broad therapeutic potential, prior efforts have all relied on genetic upregulation. Here we report that CHIP-mediated protein turnover is markedly post-translationally enhanced by direct protein kinase G (PKG) phosphorylation at S20 (mouse, S19 human). This increases CHIP binding affinity to Hsc70, CHIP protein half-life, and consequent clearance of stress- induced ubiquitinated-insoluble proteins. PKG-mediated CHIP-pS20 or expressing CHIP- S20E (phosphomimetic) reduces ischemic proteo- and cytotoxicity, whereas a phospho- silenced CHIP-S20A amplifies both. In vivo, depressing PKG activity lowers CHIP-S20 phosphorylation and protein, exacerbating proteotoxicity and heart dysfunction after ischemic injury. CHIP-S20E knock-in mice better clear ubiquitinated proteins and are cardio- protected. PKG activation provides post-translational enhancement of protein quality control via CHIP.
    [Show full text]
  • Applications of CRISPR-Cas9 Technology to Genome Editing in Glioblastoma Multiforme
    cells Review Applications of CRISPR-Cas9 Technology to Genome Editing in Glioblastoma Multiforme Nadia Al-Sammarraie and Swapan K. Ray * Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC 29209, USA; [email protected] * Correspondence: [email protected]; Tel.: +1-803-216-3420; Fax: +1-803-216-3428 Abstract: Glioblastoma multiforme (GBM) is an aggressive malignancy of the brain and spinal cord with a poor life expectancy. The low survivability of GBM patients can be attributed, in part, to its heterogeneity and the presence of multiple genetic alterations causing rapid tumor growth and resistance to conventional therapy. The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-CRISPR associated (Cas) nuclease 9 (CRISPR-Cas9) system is a cost-effective and reliable gene editing technology, which is widely used in cancer research. It leads to novel discoveries of various oncogenes that regulate autophagy, angiogenesis, and invasion and play important role in pathogenesis of various malignancies, including GBM. In this review article, we first describe the principle and methods of delivery of CRISPR-Cas9 genome editing. Second, we summarize the current knowledge and major applications of CRISPR-Cas9 to identifying and modifying the genetic regulators of the hallmark of GBM. Lastly, we elucidate the major limitations of current CRISPR-Cas9 technology in the GBM field and the future perspectives. CRISPR-Cas9 genome editing aids in identifying novel coding and non-coding transcriptional regulators of the hallmarks of GBM particularly in vitro, while work using in vivo systems requires further investigation. Citation: Al-Sammarraie, N.; Ray, S.K.
    [Show full text]
  • Regulators of G-Protein Signaling (RGS) Proteins: Region-Specific Expression of Nine Subtypes in Rat Brain
    The Journal of Neuroscience, October 15, 1997, 17(20):8024–8037 Regulators of G-Protein Signaling (RGS) Proteins: Region-Specific Expression of Nine Subtypes in Rat Brain Stephen J. Gold,1,2 YanG.Ni,1,2 Henrik G. Dohlman,3 and Eric J. Nestler1,2,3 1Laboratory of Molecular Psychiatry and Departments of 2Psychiatry and 3Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06508 The recently discovered regulators of G-protein signaling (RGS) richment in striatal regions. RGS10 mRNA is densely expressed proteins potently modulate the functioning of heterotrimeric in dentate gyrus granule cells, superficial layers of neocortex, G-proteins by stimulating the GTPase activity of G-protein a and dorsal raphe. To assess whether the expression of RGS subunits. The mRNAs for numerous subtypes of putative RGS mRNAs can be regulated, we examined the effect of an acute proteins have been identified in mammalian tissues, but little is seizure on levels of RGS7, RGS8, and RGS10 mRNAs in hip- known about their expression in brain. We performed a system- pocampus. Of the three subtypes, changes in RGS10 levels atic survey of the localization of mRNAs encoding nine of these were most pronounced, decreasing by ;40% in a time- RGSs, RGS3–RGS11, in brain by in situ hybridization. Striking dependent manner in response to a single seizure. These re- region-specific patterns of expression were observed. Five sults, which document highly specific patterns of RGS mRNA subtypes, RGS4, RGS7, RGS8, RGS9, and RGS10 mRNAs, are expression in brain and their ability to be regulated in a dynamic densely expressed in brain, whereas the other subtypes (RGS3, manner, support the view that RGS proteins may play an im- RGS5, RGS6, and RGS11) are expressed at lower density and portant role in determining the intensity and specificity of sig- in more restricted regions.
    [Show full text]
  • Therapeutically Significant Micrornas in Primary and Metastatic Brain
    cancers Review Therapeutically Significant MicroRNAs in Primary and Metastatic Brain Malignancies 1,2, 1, 1,2 Akilandeswari A. Balachandran y , Leon M. Larcher y , Suxiang Chen and Rakesh N. Veedu 1,2,* 1 Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Murdoch, WA 6150, Australia; [email protected] (A.A.B.); [email protected] (L.M.L.); [email protected] (S.C.) 2 Perron Institute for Neurological and Translational Science, Nedlands, WA 6009, Australia * Correspondence: [email protected]; Tel.: +61-893-602-803 These authors contributed equally. y Received: 20 July 2020; Accepted: 3 September 2020; Published: 7 September 2020 Simple Summary: The overall survival of brain cancer patients remains grim, with conventional therapies such as chemotherapy and radiotherapy only providing marginal benefits to patient survival. Cancers are complex, with multiple pathways being dysregulated simultaneously. Non-coding RNAs such as microRNA (miRNAs) are gaining importance due to their potential in regulating a variety of targets implicated in the pathology of cancers. This could be leveraged for the development of targeted and personalized therapies for cancers. Since miRNAs can upregulate and/or downregulate proteins, this review aims to understand the role of these miRNAs in primary and metastatic brain cancers. Here, we discuss the regulatory mechanisms of ten miRNAs that are highly dysregulated in glioblastoma and metastatic brain tumors. This will enable researchers to develop miRNA-based targeted cancer therapies and identify potential prognostic biomarkers. Abstract: Brain cancer is one among the rare cancers with high mortality rate that affects both children and adults.
    [Show full text]
  • Autophagy As a Potential Therapy for Malignant Glioma
    pharmaceuticals Review Autophagy as a Potential Therapy for Malignant Glioma Angel Escamilla-Ramírez 1 , Rosa A. Castillo-Rodríguez 2 , Sergio Zavala-Vega 3, Dolores Jimenez-Farfan 4 , Isabel Anaya-Rubio 1, Eduardo Briseño 5, Guadalupe Palencia 1, Patricia Guevara 1, Arturo Cruz-Salgado 1, Julio Sotelo 1 and Cristina Trejo-Solís 1,* 1 Departamento de Neuroinmunología, Instituto Nacional de Neurología y Neurocirugía, Ciudad de México 14269, Mexico; [email protected] (A.E.-R.); [email protected] (I.A.-R.); [email protected] (G.P.); [email protected] (P.G.); [email protected] (A.C.-S.); [email protected] (J.S.) 2 Laboratorio de Oncología Experimental, CONACYT-Instituto Nacional de Pediatría, Ciudad de México 04530, Mexico; [email protected] 3 Departamento de Patología, Instituto Nacional de Neurología y Neurocirugía, Ciudad de México 14269, Mexico; [email protected] 4 Laboratorio de Inmunología, División de Estudios de Posgrado e Investigación, Facultad de Odontología, Universidad Nacional Autónoma de México, Ciudad de México 04510, Mexico; [email protected] 5 Clínica de Neurooncología, Instituto Nacional de Neurología y Neurocirugía, Ciudad de México 14269, Mexico; [email protected] * Correspondence: [email protected]; Tel.: +52-555-060-4040 Received: 5 June 2020; Accepted: 14 July 2020; Published: 19 July 2020 Abstract: Glioma is the most frequent and aggressive type of brain neoplasm, being anaplastic astrocytoma (AA) and glioblastoma multiforme (GBM), its most malignant forms. The survival rate in patients with these neoplasms is 15 months after diagnosis, despite a diversity of treatments, including surgery, radiation, chemotherapy, and immunotherapy. The resistance of GBM to various therapies is due to a highly mutated genome; these genetic changes induce a de-regulation of several signaling pathways and result in higher cell proliferation rates, angiogenesis, invasion, and a marked resistance to apoptosis; this latter trait is a hallmark of highly invasive tumor cells, such as glioma cells.
    [Show full text]
  • Transforming Growth Factor ß1-Mediated Functional Inhibition Of
    Myelodysplastic Syndromes SUPPLEMENTARY APPENDIX Transforming growth factor 1- mediated functional inhibition of mesenchymal stromal celβls in myelodysplastic syndromes and acute myeloid leukemia Stefanie Geyh, 1* Manuel Rodríguez-Paredes, 1,2 * Paul Jäger, 1 Annemarie Koch, 1 Felix Bormann, 2 Julian Gutekunst, 2 Christoph Zilkens, 3 Ulrich Germing, 1 Guido Kobbe, 1 Frank Lyko, 2 Rainer Haas 1 and Thomas Schroeder 1 1Department of Hematology, Oncology and Clinical Immunology, University of Duesseldorf, Medical Faculty; 2Division of Epigenetics, DKFZ- ZMBH Alliance, German Cancer Research Center, Heidelberg and 3Department of Orthopedic Surgery, University of Duesseldorf, Medical Faculty, Germany *SG and MR-P contributed equally to this work. ©2018 Ferrata Storti Foundation. This is an open-access paper. doi:10.3324/haematol. 2017.186734 Received: December 19, 2017. Accepted: May 14, 2018. Pre-published: May 17, 2018. Correspondence: [email protected] Figure S1 Downregulated genes Downregulated genes Upregulated Figure S1. Heatmaps showing the 50 most upregulated and downregulated genes between the 3 healthy MSC controls and the 9 RCMD-, RAEB- and AML-derived MSC samples. Color scale depicts the rlog-transformed FPKM values for each gene and every sample. Figure S2 Downregulated genes Downregulated genes Upregulated Figure S2. Heatmaps showing the 50 most upregulated and downregulated genes between the 3 healthy MSC controls and the 3 RCMD, RAEB and AML MSC samples, respectively. Color scales depict the rlog-transformed FPKM values for each gene and every sample. Figure S3 A. B. 0.0015 *** ** <-3 -2 0.0010 RCMD RAEB AML -1 0 1 0.0005 Log2FC LTF 2 CCL26/GAPDH INHBB >3 0.0000 TGFB2 y S h D ML M A ealt ll LTF H a EGF 0.003 *** ** INHBB TGFB2 0.002 INHBB IGFBP7 0.001 GDF11 LIF/GAPDH BMP1 0.000 y L th M TNFSF12 l A FGF13 ea ll MDS H a FGF13 0.0015 * TNFSF10 TNFSF10 0.0010 0.0005 SPP1/GAPDH 0.0000 y th l AML ea H all MDS Figure S3.
    [Show full text]