Modeling of RAS Complexes Supports Roles in Cancer for Less Studied Partners H
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Snapshot: Formins Christian Baarlink, Dominique Brandt, and Robert Grosse University of Marburg, Marburg 35032, Germany
SnapShot: Formins Christian Baarlink, Dominique Brandt, and Robert Grosse University of Marburg, Marburg 35032, Germany Formin Regulators Localization Cellular Function Disease Association DIAPH1/DIA1 RhoA, RhoC Cell cortex, Polarized cell migration, microtubule stabilization, Autosomal-dominant nonsyndromic deafness (DFNA1), myeloproliferative (mDia1) phagocytic cup, phagocytosis, axon elongation defects, defects in T lymphocyte traffi cking and proliferation, tumor cell mitotic spindle invasion, defects in natural killer lymphocyte function DIAPH2 Cdc42 Kinetochore Stable microtubule attachment to kinetochore for Premature ovarian failure (mDia3) chromosome alignment DIAPH3 Rif, Cdc42, Filopodia, Filopodia formation, removing the nucleus from Increased chromosomal deletion of gene locus in metastatic tumors (mDia2) Rac, RhoB, endosomes erythroblast, endosome motility, microtubule DIP* stabilization FMNL1 (FRLα) Cdc42 Cell cortex, Phagocytosis, T cell polarity Overexpression is linked to leukemia and non-Hodgkin lymphoma microtubule- organizing center FMNL2/FRL3/ RhoC ND Cell motility Upregulated in metastatic colorectal cancer, chromosomal deletion is FHOD2 associated with mental retardation FMNL3/FRL2 Constituently Stress fi bers ND ND active DAAM1 Dishevelled Cell cortex Planar cell polarity ND DAAM2 ND ND ND Overexpressed in schizophrenia patients Human (Mouse) FHOD1 ROCK Stress fi bers Cell motility FHOD3 ND Nestin, sarcomere Organizing sarcomeres in striated muscle cells Single-nucleotide polymorphisms associated with type 1 diabetes -
Genetic Confirmation and Identification of Novel Variants For
G C A T T A C G G C A T genes Article Genetic Confirmation and Identification of Novel Variants for Glanzmann Thrombasthenia and Other Inherited Platelet Function Disorders: A Study by the Korean Pediatric Hematology Oncology Group (KPHOG) Eu Jeen Yang 1 , Ye Jee Shim 2,* , Heung Sik Kim 3, Young Tak Lim 1, Ho Joon Im 4, Kyung-Nam Koh 4, Hyery Kim 4 , Jin Kyung Suh 5, Eun Sil Park 6, Na Hee Lee 7, Young Bae Choi 8, Jeong Ok Hah 9, Jae Min Lee 10 , Jung Woo Han 11, Jae Hee Lee 12, Young-Ho Lee 13, Hye Lim Jung 14, Jung-Sook Ha 15, Chang-Seok Ki 16 and on behalf of the Benign Hematology Committee of the Korean Pediatric Hematology Oncology Group (KPHOG) † 1 Department of Pediatrics, Pusan National University School of Medicine, Pusan National University Children’s Hospital, Yangsan 50612, Korea; [email protected] (E.J.Y.); [email protected] (Y.T.L.) 2 Department of Pediatrics, Keimyung University School of Medicine, Keimyung University Dongsan Hospital, Daegu 42601, Korea 3 Department of Pediatrics, Keimyung University School of Medicine, Keimyung University Daegu Dongsan Hospital, Daegu 41931, Korea; [email protected] 4 Department of Pediatrics, University of Ulsan College of Medicine, Asan Medical Center Children’s Hospital, Seoul 05505, Korea; [email protected] (H.J.I.); [email protected] (K.-N.K.); [email protected] (H.K.) 5 Department of Pediatrics, Korea Cancer Center Hospital, Seoul 01812, Korea; [email protected] Citation: Yang, E.J.; Shim, Y.J.; Kim, 6 Department of Pediatrics, Gyeongsang National University College of Medicine, H.S.; Lim, Y.T.; Im, H.J.; Koh, K.-N.; Gyeongsang National University Hospital, Jinju 52727, Korea; [email protected] Kim, H.; Suh, J.K.; Park, E.S.; Lee, 7 Department of Pediatrics, Cha Bundang Medical Center, Cha University, Seongnam 13496, Korea; N.H.; et al. -
A Cell Line P53 Mutation Type UM
A Cell line p53 mutation Type UM-SCC 1 wt UM-SCC5 Exon 5, 157 GTC --> TTC Missense mutation by transversion (Valine --> Phenylalanine UM-SCC6 wt UM-SCC9 wt UM-SCC11A wt UM-SCC11B Exon 7, 242 TGC --> TCC Missense mutation by transversion (Cysteine --> Serine) UM-SCC22A Exon 6, 220 TAT --> TGT Missense mutation by transition (Tyrosine --> Cysteine) UM-SCC22B Exon 6, 220 TAT --> TGT Missense mutation by transition (Tyrosine --> Cysteine) UM-SCC38 Exon 5, 132 AAG --> AAT Missense mutation by transversion (Lysine --> Asparagine) UM-SCC46 Exon 8, 278 CCT --> CGT Missense mutation by transversion (Proline --> Alanine) B 1 Supplementary Methods Cell Lines and Cell Culture A panel of ten established HNSCC cell lines from the University of Michigan series (UM-SCC) was obtained from Dr. T. E. Carey at the University of Michigan, Ann Arbor, MI. The UM-SCC cell lines were derived from eight patients with SCC of the upper aerodigestive tract (supplemental Table 1). Patient age at tumor diagnosis ranged from 37 to 72 years. The cell lines selected were obtained from patients with stage I-IV tumors, distributed among oral, pharyngeal and laryngeal sites. All the patients had aggressive disease, with early recurrence and death within two years of therapy. Cell lines established from single isolates of a patient specimen are designated by a numeric designation, and where isolates from two time points or anatomical sites were obtained, the designation includes an alphabetical suffix (i.e., "A" or "B"). The cell lines were maintained in Eagle's minimal essential media supplemented with 10% fetal bovine serum and penicillin/streptomycin. -
A Negative-Feedback Loop Regulating ERK1/2 Activation and Mediated by Rasgpr2 Phosphorylation
HHS Public Access Author manuscript Author ManuscriptAuthor Manuscript Author Biochem Manuscript Author Biophys Res Commun Manuscript Author . Author manuscript; available in PMC 2017 May 20. Published in final edited form as: Biochem Biophys Res Commun. 2016 May 20; 474(1): 193–198. doi:10.1016/j.bbrc.2016.04.100. A negative-feedback loop regulating ERK1/2 activation and mediated by RasGPR2 phosphorylation Jinqi Ren#1, Aaron A. Cook#2, Wolfgang Bergmeier2, and John Sondek1,2,3 1Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599 2Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599 3Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599 # These authors contributed equally to this work. Abstract The dynamic regulation of ERK1 and −2 (ERK1/2) is required for precise signal transduction controlling cell proliferation, differentiation, and survival. However, the underlying mechanisms regulating the activation of ERK1/2 are not completely understood. In this study, we show that phosphorylation of RasGRP2, a guanine nucleotide exchange factor (GEF), inhibits its ability to activate the small GTPase Rap1 that ultimately leads to decreased activation of ERK1/2 in cells. ERK2 phosphorylates RasGRP2 at Ser394 located in the linker region implicated in its autoinhibition. These studies identify RasGRP2 as a novel substrate of ERK1/2 and define a negative-feedback loop that regulates the BRaf–MEK–ERK signaling cascade. This negative- feedback loop determines the amplitude and duration of active ERK1/2. Keywords RasGRP2; ERK1/2 signaling; negative-feedback loop; phosphorylation; GEF; CalDAG-GEFI Introduction The Ras-Raf-MEK-ERK signaling pathway is essential for many cellular processes, including growth, cell-cycle progression, differentiation, and apoptosis. -
Wnt/Β-Catenin Signaling Pathway Induces Autophagy
Yun et al. Cell Death and Disease (2020) 11:771 https://doi.org/10.1038/s41419-020-02988-8 Cell Death & Disease ARTICLE Open Access Wnt/β-catenin signaling pathway induces autophagy-mediated temozolomide-resistance in human glioblastoma Eun-Jin Yun 1,SangwooKim2,Jer-TsongHsieh3,4 and Seung Tae Baek 5,6 Abstract Temozolomide (TMZ) is widely used for treating glioblastoma multiforme (GBM), however, the treatment of such brain tumors remains a challenge due to the development of resistance. Increasing studies have found that TMZ treatment could induce autophagy that may link to therapeutic resistance in GBM, but, the precise mechanisms are not fully understood. Understanding the molecular mechanisms underlying the response of GBM to chemotherapy is paramount for developing improved cancer therapeutics. In this study, we demonstrated that the loss of DOC-2/DAB2 interacting protein (DAB2IP) is responsible for TMZ-resistance in GBM through ATG9B. DAB2IP sensitized GBM to TMZ and suppressed TMZ-induced autophagy by negatively regulating ATG9B expression. A higher level of ATG9B expression was associated with GBM compared to low-grade glioma. The knockdown of ATG9B expression in GBM cells suppressed TMZ-induced autophagy as well as TMZ-resistance. Furthermore, we showed that DAB2IP negatively regulated ATG9B expression by blocking the Wnt/β-catenin pathway. To enhance the benefit of TMZ and avoid therapeutic resistance, effective combination strategies were tested using a small molecule inhibitor blocking the Wnt/ β-catenin pathway in addition to TMZ. The combination treatment synergistically enhanced the efficacy of TMZ in GBM cells. In conclusion, the present study identified the mechanisms of TMZ-resistance of GBM mediated by DAB2IP 1234567890():,; 1234567890():,; 1234567890():,; 1234567890():,; and ATG9B which provides insight into a potential strategy to overcome TMZ chemo-resistance. -
The Endocytic Membrane Trafficking Pathway Plays a Major Role
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by University of Liverpool Repository RESEARCH ARTICLE The Endocytic Membrane Trafficking Pathway Plays a Major Role in the Risk of Parkinson’s Disease Sara Bandres-Ciga, PhD,1,2 Sara Saez-Atienzar, PhD,3 Luis Bonet-Ponce, PhD,4 Kimberley Billingsley, MSc,1,5,6 Dan Vitale, MSc,7 Cornelis Blauwendraat, PhD,1 Jesse Raphael Gibbs, PhD,7 Lasse Pihlstrøm, MD, PhD,8 Ziv Gan-Or, MD, PhD,9,10 The International Parkinson’s Disease Genomics Consortium (IPDGC), Mark R. Cookson, PhD,4 Mike A. Nalls, PhD,1,11 and Andrew B. Singleton, PhD1* 1Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA 2Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), Granada, Spain 3Transgenics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA 4Cell Biology and Gene Expression Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA 5Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom 6Department of Pathophysiology, University of Tartu, Tartu, Estonia 7Computational Biology Group, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA 8Department of Neurology, Oslo University Hospital, Oslo, Norway 9Department of Neurology and Neurosurgery, Department of Human Genetics, McGill University, Montréal, Quebec, Canada 10Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada 11Data Tecnica International, Glen Echo, Maryland, USA ABSTRACT studies, summary-data based Mendelian randomization Background: PD is a complex polygenic disorder. -
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. -
Rabbit Anti-DAB2IP Rabbit Anti-DAB2IP
Qty: 100 μg/400 μL Rabbit anti-DAB2IP Catalog No. 487300 Lot No. Rabbit anti-DAB2IP FORM This polyclonal antibody is supplied as a 400 µL aliquot at a concentration of 0.25 mg/mL in phosphate buffered saline (pH 7.4) containing 0.1% sodium azide. This antibody is epitope-affinity purified from rabbit antiserum. PAD: ZMD.689 IMMUNOGEN Synthetic peptide derived from the C-terminal region of the human DAB2IP protein (Accession# NP_619723), which is identical to mouse and rat sequence. SPECIFICITY This antibody is specific for the DAB2IP (DAB2 interacting protein, AIP1, DIP1/2) protein. On Western blots, it identifies the target band at ~110 kDa. REACTIVITY Reactivity has been confirmed with human DU145, SK-N-MC and rat B49 cell lysates. Based on amino acid sequence homology, reactivity with mouse is expected. Sample Western Immuno- Immuno- Blotting precipitation cytochemistry Human +++ 0 ND Mouse ND ND ND Rat +++ 0 ND (Excellent +++, Good++, Poor +, No reactivity 0, Not applicable N/A, Not Determined ND) USAGE Working concentrations for specific applications should be determined by the investigator. Appropriate concentrations will be affected by several factors, including secondary antibody affinity, antigen concentration, sensitivity of detection method, temperature and length of incubations, etc. The suitability of this antibody for applications other than those listed below has not been determined. The following concentration ranges are recommended starting points for this product. Western Blotting: 1-3 μg/mL STORAGE Store at 2-8°C for up to one month. Store at –20°C for long-term storage. Avoid repeated freezing and thawing. (cont’d) www.invitrogen.com Invitrogen Corporation • 542 Flynn Rd • Camarillo • CA 93012 • Tel: 800.955.6288 • E-mail: [email protected] PI487300 (Rev 10/08) DCC-08-1089 Important Licensing Information - These products may be covered by one or more Limited Use Label Licenses (see the Invitrogen Catalog or our website, www.invitrogen.com). -
Hras Intracellular Trafficking and Signal Transduction Jodi Ho-Jung Mckay Iowa State University
Iowa State University Capstones, Theses and Retrospective Theses and Dissertations Dissertations 2007 HRas intracellular trafficking and signal transduction Jodi Ho-Jung McKay Iowa State University Follow this and additional works at: https://lib.dr.iastate.edu/rtd Part of the Biological Phenomena, Cell Phenomena, and Immunity Commons, Cancer Biology Commons, Cell Biology Commons, Genetics and Genomics Commons, and the Medical Cell Biology Commons Recommended Citation McKay, Jodi Ho-Jung, "HRas intracellular trafficking and signal transduction" (2007). Retrospective Theses and Dissertations. 13946. https://lib.dr.iastate.edu/rtd/13946 This Dissertation is brought to you for free and open access by the Iowa State University Capstones, Theses and Dissertations at Iowa State University Digital Repository. It has been accepted for inclusion in Retrospective Theses and Dissertations by an authorized administrator of Iowa State University Digital Repository. For more information, please contact [email protected]. HRas intracellular trafficking and signal transduction by Jodi Ho-Jung McKay A dissertation submitted to the graduate faculty in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY Major: Genetics Program of Study Committee: Janice E. Buss, Co-major Professor Linda Ambrosio, Co-major Professor Diane Bassham Drena Dobbs Ted Huiatt Iowa State University Ames, Iowa 2007 Copyright © Jodi Ho-Jung McKay, 2007. All rights reserved. UMI Number: 3274881 Copyright 2007 by McKay, Jodi Ho-Jung All rights reserved. UMI Microform 3274881 Copyright 2008 by ProQuest Information and Learning Company. All rights reserved. This microform edition is protected against unauthorized copying under Title 17, United States Code. ProQuest Information and Learning Company 300 North Zeeb Road P.O. -
Genetic and Genomic Analysis of Hyperlipidemia, Obesity and Diabetes Using (C57BL/6J × TALLYHO/Jngj) F2 Mice
University of Tennessee, Knoxville TRACE: Tennessee Research and Creative Exchange Nutrition Publications and Other Works Nutrition 12-19-2010 Genetic and genomic analysis of hyperlipidemia, obesity and diabetes using (C57BL/6J × TALLYHO/JngJ) F2 mice Taryn P. Stewart Marshall University Hyoung Y. Kim University of Tennessee - Knoxville, [email protected] Arnold M. Saxton University of Tennessee - Knoxville, [email protected] Jung H. Kim Marshall University Follow this and additional works at: https://trace.tennessee.edu/utk_nutrpubs Part of the Animal Sciences Commons, and the Nutrition Commons Recommended Citation BMC Genomics 2010, 11:713 doi:10.1186/1471-2164-11-713 This Article is brought to you for free and open access by the Nutrition at TRACE: Tennessee Research and Creative Exchange. It has been accepted for inclusion in Nutrition Publications and Other Works by an authorized administrator of TRACE: Tennessee Research and Creative Exchange. For more information, please contact [email protected]. Stewart et al. BMC Genomics 2010, 11:713 http://www.biomedcentral.com/1471-2164/11/713 RESEARCH ARTICLE Open Access Genetic and genomic analysis of hyperlipidemia, obesity and diabetes using (C57BL/6J × TALLYHO/JngJ) F2 mice Taryn P Stewart1, Hyoung Yon Kim2, Arnold M Saxton3, Jung Han Kim1* Abstract Background: Type 2 diabetes (T2D) is the most common form of diabetes in humans and is closely associated with dyslipidemia and obesity that magnifies the mortality and morbidity related to T2D. The genetic contribution to human T2D and related metabolic disorders is evident, and mostly follows polygenic inheritance. The TALLYHO/ JngJ (TH) mice are a polygenic model for T2D characterized by obesity, hyperinsulinemia, impaired glucose uptake and tolerance, hyperlipidemia, and hyperglycemia. -
Disabled Homolog 2 Interactive Protein Functions As a Tumor Suppressor in Osteosarcoma Cells
ONCOLOGY LETTERS 16: 703-712, 2018 Disabled homolog 2 interactive protein functions as a tumor suppressor in osteosarcoma cells JIANAN HE1,5, SHUAI HUANG2, ZHENHUA LIN3, JIQIN ZHANG4, JIALIN SU4, WEIDONG JI4 and XINGMO LIU1 1Department of Orthopaedic Surgery, The Sixth Affiliated Hospital of Sun Yat‑sun University, Guangzhou, Guangdong 510655; 2Department of Orthopaedic Surgery, The First Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510080; 3Department of Orthopaedic Surgery, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi 530021; 4Center for Translational Medicine, The First Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510080; 5Department of Interventional Radiology, The Fifth Affiliated Hospital of Sun Yat-sun University, Zhuhai, Guangdong 519000, P.R. China Received April 2, 2016; Accepted June 16, 2017 DOI: 10.3892/ol.2018.8776 Abstract. The disabled homolog 2 interactive protein osteosarcoma will develop distant metastasis (2). Owing to the (DAB2IP) gene is a member of the family of Ras GTPases development of multidisciplinary therapy, the mortality rate and functions as a tumor suppressor in many types of carci- for patients with osteosarcoma has been decreasing in recent noma; however, its function in osteosarcoma remains unclear. years. Nevertheless, patients continue to exhibit a high risk The aim of the present study was to determine the function of of metastasis and/or recurrence (1,2). Previous studies have DAB2IP in osteosarcoma and normal bone cells in vitro. The indicated that several genetic aberrations are associated with expression of DAB2IP protein was assessed in osteoblast and tumor initiation and osteosarcoma progression (3,4). Thus, osteosarcoma cell lines by western blot analysis. -
Mechanistic Characterization of RASGRP1 Variants Identifies an Hnrnp K-Regulated Transcriptional Enhancer Contributing to SLE Susceptibility
bioRxiv preprint doi: https://doi.org/10.1101/568790; this version posted March 6, 2019. 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. Mechanistic characterization of RASGRP1 variants identifies an hnRNP K-regulated transcriptional enhancer contributing to SLE susceptibility Julio E. Molineros1*, Bhupinder Singh1*, Chikashi Terao2,3, Yukinori Okada4, Jakub Kaplan1, Barbara McDaniel1, Shuji Akizuki3, Celi Sun1, Carol Webb5, Loren L. Looger6, Swapan K. Nath1 1Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA 2Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan. 3Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan. 4Department of Statistical Genetics, Osaka University Graduate School of Medicine, Osaka, Japan 5Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA 6Howard Hughes Medical Institute, Janelia Research Campus, Ashburn, VA, USA *Contributed equally Corresponding author Swapan K. Nath, Ph.D. Member Arthritis & Clinical Immunology Program Oklahoma Medical Research Foundation 825 NE 13th St. Oklahoma City, OK 73104 Ph: (405)-271-7765 Fax: (405)-271-4110 [email protected] 1 bioRxiv preprint doi: https://doi.org/10.1101/568790; this version posted March 6, 2019. 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.