Recombinant Human Chloride Intracellular Channel Protein 5/CLIC5 (N-6His)

Total Page:16

File Type:pdf, Size:1020Kb

Recombinant Human Chloride Intracellular Channel Protein 5/CLIC5 (N-6His) 9853 Pacific Heights Blvd. Suite D. San Diego, CA 92121, USA Tel: 858-263-4982 Email: [email protected] 32-7190: Recombinant Human Chloride Intracellular Channel Protein 5/CLIC5 (N-6His) Gene : CLIC5 Gene ID : 53405 Uniprot ID : Q9NZA1 Description Source: E.coli. MW :30.3kD. Recombinant Human CLIC5 is produced by our E.coli expression system and the target gene encoding Met1-Ser251 is expressed with a 6His tag at the N-terminus. Chloride Intracellular Channel Protein 5 (CLIC5) is a single-pass membrane protein which belongs to the chloride channel CLIC family. It contains one GST C-terminal domain. Chloride intracellular channels are involved in chloride ion transport within various subcellular compartments. CLIC5 can insert into membranes and form selective ion channels regulated by actin that may transport chloride ions. It may play a role in the regulation of transepithelial ion absorption and secretion. CLIC5 specifically associates with the cytoskeleton of placenta microvilli. CLIC5 is required for the development and/or maintenance of the proper glomerular endothelial cell and podocyte architecture. Product Info Amount : 10 µg / 50 µg Content : Lyophilized from a 0.2 µm filtered solution of 20mM PB, 150mM NaCl, pH 7.4. Lyophilized protein should be stored at -20°C, though stable at room temperature for 3 weeks. Storage condition : Reconstituted protein solution can be stored at 4-7°C for 2-7 days. Aliquots of reconstituted samples are stable at -20°C for 3 months. Amino Acid : MGSSHHHHHHSSGLVPRGSHMTDSATANGDDRDPEIELFVKAGIDGESIGNCPFSQRLFMILWLK GVVFNVTTVDLKRKPADLHNLAPGTHPPFLTFNGDVKTDVNKIEEFLEETLTPEKYPKLAAKHRESN TAGIDIFSKFSAYIKNTKQQNNAALERGLTKALKKLDDYLNTPLPEEIDANTCGEDKGSRRKFLDGD ELTLADCNLLPKLHVVKIVAKKYRNYDIPAEMTGLWRYLKNAYARDEFTNTCAADSEIELAYADVAK RLSRS Application Note Always centrifuge tubes before opening. Do not mix by vortex or pipetting. It is not recommended to reconstitute to a concentration less than 100 µg/ml. Dissolve the lyophilized protein in ddH2O. Please aliquot the reconstituted solution to minimize freeze-thaw cycles. Endotoxin : Less than 0.1 ng/µg (1 IEU/µg) as determined by LAL test. For Research Use Only. Not for use in diagnostic/therapeutics procedures..
Recommended publications
  • Screening and Identification of Key Biomarkers in Clear Cell Renal Cell Carcinoma Based on Bioinformatics Analysis
    bioRxiv preprint doi: https://doi.org/10.1101/2020.12.21.423889; this version posted December 23, 2020. 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. Screening and identification of key biomarkers in clear cell renal cell carcinoma based on bioinformatics analysis Basavaraj Vastrad1, Chanabasayya Vastrad*2 , Iranna Kotturshetti 1. Department of Biochemistry, Basaveshwar College of Pharmacy, Gadag, Karnataka 582103, India. 2. Biostatistics and Bioinformatics, Chanabasava Nilaya, Bharthinagar, Dharwad 580001, Karanataka, India. 3. Department of Ayurveda, Rajiv Gandhi Education Society`s Ayurvedic Medical College, Ron, Karnataka 562209, India. * Chanabasayya Vastrad [email protected] Ph: +919480073398 Chanabasava Nilaya, Bharthinagar, Dharwad 580001 , Karanataka, India bioRxiv preprint doi: https://doi.org/10.1101/2020.12.21.423889; this version posted December 23, 2020. 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. Abstract Clear cell renal cell carcinoma (ccRCC) is one of the most common types of malignancy of the urinary system. The pathogenesis and effective diagnosis of ccRCC have become popular topics for research in the previous decade. In the current study, an integrated bioinformatics analysis was performed to identify core genes associated in ccRCC. An expression dataset (GSE105261) was downloaded from the Gene Expression Omnibus database, and included 26 ccRCC and 9 normal kideny samples. Assessment of the microarray dataset led to the recognition of differentially expressed genes (DEGs), which was subsequently used for pathway and gene ontology (GO) enrichment analysis.
    [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]
  • Bi-Allelic Novel Variants in CLIC5 Identified in a Cameroonian
    G C A T T A C G G C A T genes Article Bi-Allelic Novel Variants in CLIC5 Identified in a Cameroonian Multiplex Family with Non-Syndromic Hearing Impairment Edmond Wonkam-Tingang 1, Isabelle Schrauwen 2 , Kevin K. Esoh 1 , Thashi Bharadwaj 2, Liz M. Nouel-Saied 2 , Anushree Acharya 2, Abdul Nasir 3 , Samuel M. Adadey 1,4 , Shaheen Mowla 5 , Suzanne M. Leal 2 and Ambroise Wonkam 1,* 1 Division of Human Genetics, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa; [email protected] (E.W.-T.); [email protected] (K.K.E.); [email protected] (S.M.A.) 2 Center for Statistical Genetics, Sergievsky Center, Taub Institute for Alzheimer’s Disease and the Aging Brain, and the Department of Neurology, Columbia University Medical Centre, New York, NY 10032, USA; [email protected] (I.S.); [email protected] (T.B.); [email protected] (L.M.N.-S.); [email protected] (A.A.); [email protected] (S.M.L.) 3 Synthetic Protein Engineering Lab (SPEL), Department of Molecular Science and Technology, Ajou University, Suwon 443-749, Korea; [email protected] 4 West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), University of Ghana, Accra LG 54, Ghana 5 Division of Haematology, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa; [email protected] * Correspondence: [email protected]; Tel.: +27-21-4066-307 Received: 28 September 2020; Accepted: 20 October 2020; Published: 23 October 2020 Abstract: DNA samples from five members of a multiplex non-consanguineous Cameroonian family, segregating prelingual and progressive autosomal recessive non-syndromic sensorineural hearing impairment, underwent whole exome sequencing.
    [Show full text]
  • Transcriptomic and Proteomic Profiling Provides Insight Into
    BASIC RESEARCH www.jasn.org Transcriptomic and Proteomic Profiling Provides Insight into Mesangial Cell Function in IgA Nephropathy † † ‡ Peidi Liu,* Emelie Lassén,* Viji Nair, Celine C. Berthier, Miyuki Suguro, Carina Sihlbom,§ † | † Matthias Kretzler, Christer Betsholtz, ¶ Börje Haraldsson,* Wenjun Ju, Kerstin Ebefors,* and Jenny Nyström* *Department of Physiology, Institute of Neuroscience and Physiology, §Proteomics Core Facility at University of Gothenburg, University of Gothenburg, Gothenburg, Sweden; †Division of Nephrology, Department of Internal Medicine and Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan; ‡Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan; |Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden; and ¶Integrated Cardio Metabolic Centre, Karolinska Institutet Novum, Huddinge, Sweden ABSTRACT IgA nephropathy (IgAN), the most common GN worldwide, is characterized by circulating galactose-deficient IgA (gd-IgA) that forms immune complexes. The immune complexes are deposited in the glomerular mesangium, leading to inflammation and loss of renal function, but the complete pathophysiology of the disease is not understood. Using an integrated global transcriptomic and proteomic profiling approach, we investigated the role of the mesangium in the onset and progression of IgAN. Global gene expression was investigated by microarray analysis of the glomerular compartment of renal biopsy specimens from patients with IgAN (n=19) and controls (n=22). Using curated glomerular cell type–specific genes from the published literature, we found differential expression of a much higher percentage of mesangial cell–positive standard genes than podocyte-positive standard genes in IgAN. Principal coordinate analysis of expression data revealed clear separation of patient and control samples on the basis of mesangial but not podocyte cell–positive standard genes.
    [Show full text]
  • Transcriptomic Uniqueness and Commonality of the Ion Channels and Transporters in the Four Heart Chambers Sanda Iacobas1, Bogdan Amuzescu2 & Dumitru A
    www.nature.com/scientificreports OPEN Transcriptomic uniqueness and commonality of the ion channels and transporters in the four heart chambers Sanda Iacobas1, Bogdan Amuzescu2 & Dumitru A. Iacobas3,4* Myocardium transcriptomes of left and right atria and ventricles from four adult male C57Bl/6j mice were profled with Agilent microarrays to identify the diferences responsible for the distinct functional roles of the four heart chambers. Female mice were not investigated owing to their transcriptome dependence on the estrous cycle phase. Out of the quantifed 16,886 unigenes, 15.76% on the left side and 16.5% on the right side exhibited diferential expression between the atrium and the ventricle, while 5.8% of genes were diferently expressed between the two atria and only 1.2% between the two ventricles. The study revealed also chamber diferences in gene expression control and coordination. We analyzed ion channels and transporters, and genes within the cardiac muscle contraction, oxidative phosphorylation, glycolysis/gluconeogenesis, calcium and adrenergic signaling pathways. Interestingly, while expression of Ank2 oscillates in phase with all 27 quantifed binding partners in the left ventricle, the percentage of in-phase oscillating partners of Ank2 is 15% and 37% in the left and right atria and 74% in the right ventricle. The analysis indicated high interventricular synchrony of the ion channels expressions and the substantially lower synchrony between the two atria and between the atrium and the ventricle from the same side. Starting with crocodilians, the heart pumps the blood through the pulmonary circulation and the systemic cir- culation by the coordinated rhythmic contractions of its upper lef and right atria (LA, RA) and lower lef and right ventricles (LV, RV).
    [Show full text]
  • Data Supporting Characterization of CLIC1, CLIC4, CLIC5 and Dmclic Antibodies and Localization of Clics in Endoplasmic Reticulum of Cardiomyocytes
    Data in Brief 7 (2016) 1038–1044 Contents lists available at ScienceDirect Data in Brief journal homepage: www.elsevier.com/locate/dib Data Article Data supporting characterization of CLIC1, CLIC4, CLIC5 and DmCLIC antibodies and localization of CLICs in endoplasmic reticulum of cardiomyocytes Devasena Ponnalagu a, Shubha Gururaja Rao a, Jason Farber a, Wenyu Xin a, Ahmed Tafsirul Hussain a, Kajol Shah a, Soichi Tanda b, Mark A. Berryman c, John C. Edwards d, Harpreet Singh a,n a Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, PA 19102, United States b Department of Biological Sciences, Ohio University, Athens, OH 45701, United States c Department of Biomedical Sciences, Ohio University, Athens, OH 45701, United States d Division of Nephrology, St. Louis University, St. Louis, MO 63110, United States article info abstract Article history: Chloride intracellular channel (CLICs) proteins show 60–70% Received 22 January 2016 sequence identity to each other, and exclusively localize to the Received in revised form intracellular organelle membranes and cytosol. In support of 22 February 2016 our recent publication, “Molecular identity of cardiac mito- Accepted 16 March 2016 chondrial chloride intracellular channel proteins” (Ponnalagu Available online 26 March 2016 et al., 2016) [1], it was important to characterize the specificity Keywords: of different CLIC paralogs/ortholog (CLIC1, CLIC4, CLIC5 and Chloride intracellular channels DmCLIC) antibodies used to decipher their localization in car- Endoplasmic reticulum diac cells. In addition, localization of CLICs in the other orga- Mitochondria nelles such as endoplasmic reticulum (ER) of cardiomyocytes Cardiomyocytes was established. This article also provides data on the different primers used to show the relative abundance of CLIC paralogs in cardiac tissue and the specificity of the various CLIC antibodies used.
    [Show full text]
  • Application of Microrna Database Mining in Biomarker Discovery and Identification of Therapeutic Targets for Complex Disease
    Article Application of microRNA Database Mining in Biomarker Discovery and Identification of Therapeutic Targets for Complex Disease Jennifer L. Major, Rushita A. Bagchi * and Julie Pires da Silva * Department of Medicine, Division of Cardiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; [email protected] * Correspondence: [email protected] (R.A.B.); [email protected] (J.P.d.S.) Supplementary Tables Methods Protoc. 2021, 4, 5. https://doi.org/10.3390/mps4010005 www.mdpi.com/journal/mps Methods Protoc. 2021, 4, 5. https://doi.org/10.3390/mps4010005 2 of 25 Table 1. List of all hsa-miRs identified by Human microRNA Disease Database (HMDD; v3.2) analysis. hsa-miRs were identified using the term “genetics” and “circulating” as input in HMDD. Targets CAD hsa-miR-1 Targets IR injury hsa-miR-423 Targets Obesity hsa-miR-499 hsa-miR-146a Circulating Obesity Genetics CAD hsa-miR-423 hsa-miR-146a Circulating CAD hsa-miR-149 hsa-miR-499 Circulating IR Injury hsa-miR-146a Circulating Obesity hsa-miR-122 Genetics Stroke Circulating CAD hsa-miR-122 Circulating Stroke hsa-miR-122 Genetics Obesity Circulating Stroke hsa-miR-26b hsa-miR-17 hsa-miR-223 Targets CAD hsa-miR-340 hsa-miR-34a hsa-miR-92a hsa-miR-126 Circulating Obesity Targets IR injury hsa-miR-21 hsa-miR-423 hsa-miR-126 hsa-miR-143 Targets Obesity hsa-miR-21 hsa-miR-223 hsa-miR-34a hsa-miR-17 Targets CAD hsa-miR-223 hsa-miR-92a hsa-miR-126 Targets IR injury hsa-miR-155 hsa-miR-21 Circulating CAD hsa-miR-126 hsa-miR-145 hsa-miR-21 Targets Obesity hsa-mir-223 hsa-mir-499 hsa-mir-574 Targets IR injury hsa-mir-21 Circulating IR injury Targets Obesity hsa-mir-21 Targets CAD hsa-mir-22 hsa-mir-133a Targets IR injury hsa-mir-155 hsa-mir-21 Circulating Stroke hsa-mir-145 hsa-mir-146b Targets Obesity hsa-mir-21 hsa-mir-29b Methods Protoc.
    [Show full text]
  • Human Induced Pluripotent Stem Cell–Derived Podocytes Mature Into Vascularized Glomeruli Upon Experimental Transplantation
    BASIC RESEARCH www.jasn.org Human Induced Pluripotent Stem Cell–Derived Podocytes Mature into Vascularized Glomeruli upon Experimental Transplantation † Sazia Sharmin,* Atsuhiro Taguchi,* Yusuke Kaku,* Yasuhiro Yoshimura,* Tomoko Ohmori,* ‡ † ‡ Tetsushi Sakuma, Masashi Mukoyama, Takashi Yamamoto, Hidetake Kurihara,§ and | Ryuichi Nishinakamura* *Department of Kidney Development, Institute of Molecular Embryology and Genetics, and †Department of Nephrology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan; ‡Department of Mathematical and Life Sciences, Graduate School of Science, Hiroshima University, Hiroshima, Japan; §Division of Anatomy, Juntendo University School of Medicine, Tokyo, Japan; and |Japan Science and Technology Agency, CREST, Kumamoto, Japan ABSTRACT Glomerular podocytes express proteins, such as nephrin, that constitute the slit diaphragm, thereby contributing to the filtration process in the kidney. Glomerular development has been analyzed mainly in mice, whereas analysis of human kidney development has been minimal because of limited access to embryonic kidneys. We previously reported the induction of three-dimensional primordial glomeruli from human induced pluripotent stem (iPS) cells. Here, using transcription activator–like effector nuclease-mediated homologous recombination, we generated human iPS cell lines that express green fluorescent protein (GFP) in the NPHS1 locus, which encodes nephrin, and we show that GFP expression facilitated accurate visualization of nephrin-positive podocyte formation in
    [Show full text]
  • Supplementary Figure S1
    Supplementary Figure S1 Supplementary Figure S2 Supplementary Figure S3 Supplementary Figure S4 Supplementary Figure S5 Supplementary Figure S6 Supplementary Table 1: Baseline demographics from included patients Bulk transcriptomics Single cell transcriptomics Organoids IBD non-IBD controls IBD non-IBD controls IBD non-IBD controls (n = 351) (n = 51) (n = 6 ) (n= 5) (n = 8) (n =8) Disease - Crohn’s disease 193 (55.0) N.A. 6 (100.0) N.A. 0 (0.0) N.A. - Ulcerative colitis 158 (45.0) 0 (0.0) 8 (100.0) Women, n (%) 183 (52.1) 34 (66.7) 5 (83.3) 1 (20.0) 4 (50.0) 5 (62.5) Age, years, median [IQR] 41.8 (26.7 – 53.0) 57.0 (41.0 – 63.0) 42.7 (38.5 – 49.5) 71.0 (52.5 – 73.0) 41.3 (35.9 – 46.5) 45.0 (30.5 – 55.9) Disease duration, years, median [IQR] 7.9 (2.0 – 16.8) N.A. 13.4 (5.8 – 22.1) N.A 10.5 (7.8 – 12.7) N.A. Disease location, n (%) - Ileal (L1) 41 (21.3) 3 (50.0) - Colonic (L2) 23 (11.9) N.A. 0 (0.0) N.A. N.A. N.A. - Ileocolonic (L3) 129 (66.8) 3 (50.0) - Upper GI modifier (+L4) 57 (29.5) 0 (0.0) - Proctitis (E1) 13 (8.2) 1 (12.5) - Left-sided colitis (E2) 85 (53.8) N.A. N.A. N.A. 1 (12.5) N.A. - Extensive colitis (E3) 60 (38.0) 6 (75.0) Disease behaviour, n (%) - Inflammatory (B1) 95 (49.2) 0 (0.0) - Fibrostenotic (B2) 55 (28.5) N.A.
    [Show full text]
  • NIH Public Access Author Manuscript FEBS Lett
    NIH Public Access Author Manuscript FEBS Lett. Author manuscript; available in PMC 2011 May 17. NIH-PA Author ManuscriptPublished NIH-PA Author Manuscript in final edited NIH-PA Author Manuscript form as: FEBS Lett. 2010 May 17; 584(10): 2102±2111. doi:10.1016/j.febslet.2010.01.037. Chloride Channels of Intracellular Membranes John C. Edwards* and Christina R. Kahl UNC Kidney Center and the Division of Nephrology and Hypertension, Department of Medicine, University of North Carolina at Chapel Hill Abstract Proteins implicated as intracellular chloride channels include the intracellular ClC proteins, the bestrophins, the cystic fibrosis transmembrane conductance regulator, the CLICs, and the recently described Golgi pH regulator. This paper examines current hypotheses regarding roles of intracellular chloride channels and reviews the evidence supporting a role in intracellular chloride transport for each of these proteins. Keywords chloride channel; ClC; CLIC; bestrophin; GPHR The study of chloride channels of intracellular membranes has seen enormous advances over the past two decades and exciting recent developments have sparked renewed interest in this field. The discovery of important roles for intracellular chloride channels in human disease processes as diverse as retinal macular dystrophy, osteopetrosis, renal proximal tubule dysfunction, and angiogenesis have highlighted the importance of these molecules in critical cellular activities. Startling discoveries regarding the intracellular ClC family of proteins have forced a re-examination
    [Show full text]
  • Engineered Type 1 Regulatory T Cells Designed for Clinical Use Kill Primary
    ARTICLE Acute Myeloid Leukemia Engineered type 1 regulatory T cells designed Ferrata Storti Foundation for clinical use kill primary pediatric acute myeloid leukemia cells Brandon Cieniewicz,1* Molly Javier Uyeda,1,2* Ping (Pauline) Chen,1 Ece Canan Sayitoglu,1 Jeffrey Mao-Hwa Liu,1 Grazia Andolfi,3 Katharine Greenthal,1 Alice Bertaina,1,4 Silvia Gregori,3 Rosa Bacchetta,1,4 Norman James Lacayo,1 Alma-Martina Cepika1,4# and Maria Grazia Roncarolo1,2,4# Haematologica 2021 Volume 106(10):2588-2597 1Department of Pediatrics, Division of Stem Cell Transplantation and Regenerative Medicine, Stanford School of Medicine, Stanford, CA, USA; 2Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford School of Medicine, Stanford, CA, USA; 3San Raffaele Telethon Institute for Gene Therapy, Milan, Italy and 4Center for Definitive and Curative Medicine, Stanford School of Medicine, Stanford, CA, USA *BC and MJU contributed equally as co-first authors #AMC and MGR contributed equally as co-senior authors ABSTRACT ype 1 regulatory (Tr1) T cells induced by enforced expression of interleukin-10 (LV-10) are being developed as a novel treatment for Tchemotherapy-resistant myeloid leukemias. In vivo, LV-10 cells do not cause graft-versus-host disease while mediating graft-versus-leukemia effect against adult acute myeloid leukemia (AML). Since pediatric AML (pAML) and adult AML are different on a genetic and epigenetic level, we investigate herein whether LV-10 cells also efficiently kill pAML cells. We show that the majority of primary pAML are killed by LV-10 cells, with different levels of sensitivity to killing. Transcriptionally, pAML sensitive to LV-10 killing expressed a myeloid maturation signature.
    [Show full text]
  • Antisense Suppression of the Chloride Intracellular Channel Family Induces Apoptosis, Enhances Tumor Necrosis Factor A-Induced Apoptosis, and Inhibits Tumor Growth
    Research Article Antisense Suppression of the Chloride Intracellular Channel Family Induces Apoptosis, Enhances Tumor Necrosis Factor a-Induced Apoptosis, and Inhibits Tumor Growth Kwang S. Suh, Michihiro Mutoh, Michael Gerdes, John M. Crutchley, Tomoko Mutoh, Lindsay E. Edwards, Rebecca A. Dumont, Pooja Sodha, Christina Cheng, Adam Glick, and Stuart H. Yuspa Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland Abstract CLICs are also found in a soluble form in the cytoplasm (2–5). mtCLIC/CLIC4 is a p53 and tumor necrosis factor a (TNFa) Crystallographic analysis of the structure of soluble CLIC1 regulated intracellular chloride channel protein that local- indicates homology to the glutathione transferase family of izes to cytoplasm and organelles and induces apoptosis proteins. It is hypothesized that soluble CLICs may become when overexpressed in several cell types of mouse and activated as anion channels or channel regulators when ‘‘auto- humanorigin.CLIC4iselevatedduringTNFa-induced inserted’’ into intracellular membranes (6). apoptosis in human osteosarcoma cell lines. In contrast, Among the CLIC family proteins, the biological functions of inhibition of NFKB results in an increase in TNFa-mediated CLIC4 have been most thoroughly studied. CLIC4 is expressed in apoptosis with a decrease in CLIC4 protein levels. Cell lines many cell types. In skin keratinocytes, CLIC4 was first localized to expressing an inducible CLIC4-antisense construct that also mitochondria and cytoplasm and later was localized specifically reduces the expression of several other chloride intracellular to the inner mitochondrial membrane by immunogold electron channel (CLIC) family proteins were established in the microscopy (7, 8). Other reports have localized CLIC4 in the trans- human osteosarcoma lines SaOS and U2OS cells and Golgi network in pancreatic cells, endoplasmic reticulum in rat a malignant derivative of the mouse squamous papilloma hippocampal HT-4 cells, and large dense core vesicles in line SP1.
    [Show full text]