Genomic Patterns of Transcription-Replication Interactions in Mouse Primary B Cells
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
Polyphosphate-Dependent Synthesis of ATP and ADP by the Family-2 Polyphosphate Kinases in Bacteria
Polyphosphate-dependent synthesis of ATP and ADP by the family-2 polyphosphate kinases in bacteria Boguslaw Noceka, Samvel Kochinyanb, Michael Proudfootb, Greg Brownb, Elena Evdokimovaa,b, Jerzy Osipiuka, Aled M. Edwardsa,b, Alexei Savchenkoa,b, Andrzej Joachimiaka,c,1, and Alexander F. Yakuninb,1 aMidwest Center for Structural Genomics and Structural Biology Center, Department of Biosciences, Argonne National Laboratory, 9700 South Cass Avenue, Building 202, Argonne, IL 60439; bBanting and Best Department of Medical Research, University of Toronto, Toronto, ON, Canada M5G 1L6; and cDepartment of Biochemistry and Molecular Biology, University of Chicago, 920 East 58th Street, Chicago, IL 60637 Edited by Robert Haselkorn, University of Chicago, Chicago, IL, and approved September 30, 2008 (received for review August 1, 2008) Inorganic polyphosphate (polyP) is a linear polymer of tens or hun- exopolysaccharide essential for the virulence of P. aeruginosa (12). dreds of phosphate residues linked by high-energy bonds. It is found In the social slime mold Dictyostelium discoideum, a different PPK in all organisms and has been proposed to serve as an energy source was found (DdPPK2) with sequence and properties similar to that in a pre-ATP world. This ubiquitous and abundant biopolymer plays of actin-related proteins (Arps) (14). DdPPK2 is a complex of 3 numerous and vital roles in metabolism and regulation in prokaryotes Arps (Arp1, Arp2, and Arpx) and resembles the actin family in and eukaryotes, but the underlying molecular mechanisms for most molecular weight, sequence, and filamentous structure. Remark- activities of polyP remain unknown. In prokaryotes, the synthesis and ably, DdPPK2 can polymerize into an actin-like filament concurrent utilization of polyP are catalyzed by 2 families of polyP kinases, PPK1 with the synthesis of polyP (14). -
The Cross-Talk Between Methylation and Phosphorylation in Lymphoid-Specific Helicase Drives Cancer Stem-Like Properties
Signal Transduction and Targeted Therapy www.nature.com/sigtrans ARTICLE OPEN The cross-talk between methylation and phosphorylation in lymphoid-specific helicase drives cancer stem-like properties Na Liu1,2,3, Rui Yang1,2, Ying Shi1,2, Ling Chen1,2, Yating Liu1,2, Zuli Wang1,2, Shouping Liu1,2, Lianlian Ouyang4, Haiyan Wang1,2, Weiwei Lai1,2, Chao Mao1,2, Min Wang1,2, Yan Cheng5, Shuang Liu4, Xiang Wang6, Hu Zhou7, Ya Cao1,2, Desheng Xiao1 and Yongguang Tao1,2,6 Posttranslational modifications (PTMs) of proteins, including chromatin modifiers, play crucial roles in the dynamic alteration of various protein properties and functions including stem-cell properties. However, the roles of Lymphoid-specific helicase (LSH), a DNA methylation modifier, in modulating stem-like properties in cancer are still not clearly clarified. Therefore, exploring PTMs modulation of LSH activity will be of great significance to further understand the function and activity of LSH. Here, we demonstrate that LSH is capable to undergo PTMs, including methylation and phosphorylation. The arginine methyltransferase PRMT5 can methylate LSH at R309 residue, meanwhile, LSH could as well be phosphorylated by MAPK1 kinase at S503 residue. We further show that the accumulation of phosphorylation of LSH at S503 site exhibits downregulation of LSH methylation at R309 residue, which eventually promoting stem-like properties in lung cancer. Whereas, phosphorylation-deficient LSH S503A mutant promotes the accumulation of LSH methylation at R309 residue and attenuates stem-like properties, indicating the critical roles of LSH PTMs in modulating stem-like properties. Thus, our study highlights the importance of the crosstalk between LSH PTMs in determining its activity and function in lung cancer stem-cell maintenance. -
Expression Pattern and Level of ING5 Protein in Normal and Cancer Tissues
ONCOLOGY LETTERS 17: 63-68, 2019 Expression pattern and level of ING5 protein in normal and cancer tissues XUE-FENG YANG1, DAO-FU SHEN1, SHUANG ZHAO1, TIAN-REN REN2, YANG GAO1, SHUAI SHI1, JI-CHENG WU1, HONG-ZHI SUN1 and HUA-CHUAN ZHENG1,3 1Cancer Center and Key Laboratory of Brain and Spinal Cord Injury of Liaoning Province, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121001;2 Jilin Province Forestry Bureau, Linjiang, Jilin 134600; 3Institute of Life Sciences, Jinzhou Medical University, Jinzhou, Liaoning 121001, P.R. China Received February 21, 2016; Accepted February 13, 2017 DOI: 10.3892/ol.2018.9581 Abstract. Inhibitor of growth family 5 (ING5) functions as may be involved in cell regeneration and be associated with a type-II tumor suppressor gene and exerts an important role colorectal carcinogenesis. in DNA repair, apoptotic induction, proliferative inhibition, chromatin remodeling and the invasion process. In the present Introduction study, immunohistochemistry was performed to characterize the expression profile of ING5 protein on a tissue microarray Inhibitor of growth family 5 (ING5) is a member of the ING containing mouse and human normal tissues, and human protein family and functions as a type-II tumor suppressor cancer tissues, including hepatocellular (n=62), renal clear cell gene. Human ING5 is mapped to chromosome 2q37.3 and (n=62), pancreatic (n=62), esophageal squamous cell (n=45), encodes a 28-kDa protein with 240 amino acids (1). As indi- cervical squamous cell (n=31), breast (n=144), gastric (n=196), cated in Fig. 1, ING5 protein consists of a number of domains, colorectal (n=96), endometrial (n=96) and lung carcinoma including leucine zipper like (LZL), novel conserved region (n=192). -
Progress in Understanding 2-Hydroxyglutaric Acidurias
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Springer - Publisher Connector J Inherit Metab Dis (2012) 35:571–587 DOI 10.1007/s10545-012-9462-5 METABOLIC DISSERTATION Progress in understanding 2-hydroxyglutaric acidurias Martijn Kranendijk & Eduard A. Struys & Gajja S. Salomons & Marjo S. Van der Knaap & Cornelis Jakobs Martijn Kranendijk Received: 13 December 2011 /Revised: 25 January 2012 /Accepted: 30 January 2012 /Published online: 6 March 2012 # The Author(s) 2012. This article is published with open access at Springerlink.com Abstract The organic acidurias D-2-hydroxyglutaric acidu- D2HGDH gene encoding D-2-hydroxyglutarate ria (D-2-HGA), L-2-hydroxyglutaric aciduria (L-2-HGA), dehydrogenase and combined D,L-2-hydroxyglutaric aciduria (D,L- L-2-HG L-2-hydroxyglutaric acid 2-HGA) cause neurological impairment at young age. L-2-HGA L-2-hydroxyglutaric aciduria Accumulation of D-2-hydroxyglutarate (D-2-HG) and/or L- L-2-HGDH L-2-hydroxyglutarate dehydrogenase 2-hydroxyglutarate (L-2-HG) in body fluids are the bio- enzyme chemical hallmarks of these disorders. The current review L2HGDH gene encoding L-2-hydroxyglutarate describes the knowledge gathered on 2-hydroxyglutaric dehydrogenase acidurias (2-HGA), since the description of the first patients D,L-2-HGA combined D,L-2-hydroxyglutaric aciduria in 1980. We report on the clinical, genetic, enzymatic and IDH2 gene encoding isocitrate dehydrogenase 2 metabolic characterization of D-2-HGA type I, D-2-HGA 2-KG 2-ketoglutaric acid type II, L-2-HGA and D,L-2-HGA, whereas for D-2-HGA HOT hydroxyacid-oxoacid transhydrogenase type I and type II novel clinical information is presented enzyme which was derived from questionnaires. -
Atg4b Antibody A
Revision 1 C 0 2 - t Atg4B Antibody a e r o t S Orders: 877-616-CELL (2355) [email protected] Support: 877-678-TECH (8324) 9 9 Web: [email protected] 2 www.cellsignal.com 5 # 3 Trask Lane Danvers Massachusetts 01923 USA For Research Use Only. Not For Use In Diagnostic Procedures. Applications: Reactivity: Sensitivity: MW (kDa): Source: UniProt ID: Entrez-Gene Id: WB H M R Endogenous 48 Rabbit Q9Y4P1 23192 Product Usage Information 2. Ohsumi, Y. (2001) Nat Rev Mol Cell Biol 2, 211-6. 3. Kabeya, Y. et al. (2000) EMBO J 19, 5720-8. Application Dilution 4. Kabeya, Y. et al. (2004) J Cell Sci 117, 2805-12. 5. Mariño, G. et al. (2003) J Biol Chem 278, 3671-8. Western Blotting 1:1000 6. Sou, Y.S. et al. (2008) Mol Biol Cell 19, 4762-75. 7. Hemelaar, J. et al. (2003) J Biol Chem 278, 51841-50. Storage 8. Kabeya, Y. et al. (2004) J Cell Sci 117, 2805-12. 9. Tanida, I. et al. (2004) J Biol Chem 279, 36268-76. Supplied in 10 mM sodium HEPES (pH 7.5), 150 mM NaCl, 100 µg/ml BSA and 50% 10. Fujita, N. et al. (2008) Mol Biol Cell 19, 4651-9. glycerol. Store at –20°C. Do not aliquot the antibody. 11. Fujita, N. et al. (2009) Autophagy 5, 88-9. Specificity / Sensitivity Atg4B Antibody detects endogenous levels of total Atg4B protein. This antibody detects a band at ~27 kDa of unknown origin. Species Reactivity: Human, Mouse, Rat Source / Purification Polyclonal antibodies are produced by immunizing animals with a synthetic peptide corresponding to residues surrounding Ser372 of human Atg4B protein. -
The Tumor Suppressor ING5 Is a Dimeric, Bivalent Recognition Molecule of the Histone H3k4me3 Mark
Article The Tumor Suppressor ING5 Is a Dimeric, Bivalent Recognition Molecule of the Histone H3K4me3 Mark Georgina Ormaza 1,†, Jhon A. Rodríguez 1,†, Alain Ibáñez de Opakua 1, Nekane Merino 1, Maider Villate 1, Irantzu Gorroño 1, Miriam Rábano 1, Ignacio Palmero 2, Marta Vilaseca 3, Robert Kypta 1,4, María d.M. Vivanco 1, Adriana L. Rojas 1 and Francisco J. Blanco 1,5 1 - CIC bioGUNE, Parque Tecnológico de Bizkaia, 48160 Derio, Spain 2 - Instituto de Investigaciones Biomédicas “Alberto Sols”, CSIC-UAM, 28029 Madrid, Spain 3 - Institute for Research in Biomedicine, 08028 Barcelona, Spain 4 - Department of Surgery and Cancer, Imperial College London, London, W12 0NN, UK 5 - IKERBASQUE, Basque Foundation for Science, 48011 Bilbao, Spain Correspondence to Francisco J. Blanco: CIC bioGUNE, Parque Tecnológico de Bizkaia, 48160 Derio, Spain. [email protected] https://doi.org/10.1016/j.jmb.2019.04.018 Edited by M. Guss Abstract The INhibitor of Growth (ING) family of tumor suppressors regulates the transcriptional state of chromatin by recruiting remodeling complexes to sites with histone H3 trimethylated at lysine 4 (H3K4me3). This modification is recognized by the plant homeodomain (PHD) present at the C-terminus of the five ING proteins. ING5 facilitates histone H3 acetylation by the HBO1 complex, and also H4 acetylation by the MOZ/ MORF complex. We show that ING5 forms homodimers through its N-terminal domain, which folds independently into an elongated coiled-coil structure. The central region of ING5, which contains the nuclear localization sequence, is flexible and disordered, but it binds dsDNA with micromolar affinity. NMR analysis of the full-length protein reveals that the two PHD fingers of the dimer are chemically equivalent and independent of the rest of the molecule, and they bind H3K4me3 in the same way as the isolated PHD. -
Modes of Interaction of KMT2 Histone H3 Lysine 4 Methyltransferase/COMPASS Complexes with Chromatin
cells Review Modes of Interaction of KMT2 Histone H3 Lysine 4 Methyltransferase/COMPASS Complexes with Chromatin Agnieszka Bochy ´nska,Juliane Lüscher-Firzlaff and Bernhard Lüscher * ID Institute of Biochemistry and Molecular Biology, Medical School, RWTH Aachen University, Pauwelsstrasse 30, 52057 Aachen, Germany; [email protected] (A.B.); jluescher-fi[email protected] (J.L.-F.) * Correspondence: [email protected]; Tel.: +49-241-8088850; Fax: +49-241-8082427 Received: 18 January 2018; Accepted: 27 February 2018; Published: 2 March 2018 Abstract: Regulation of gene expression is achieved by sequence-specific transcriptional regulators, which convey the information that is contained in the sequence of DNA into RNA polymerase activity. This is achieved by the recruitment of transcriptional co-factors. One of the consequences of co-factor recruitment is the control of specific properties of nucleosomes, the basic units of chromatin, and their protein components, the core histones. The main principles are to regulate the position and the characteristics of nucleosomes. The latter includes modulating the composition of core histones and their variants that are integrated into nucleosomes, and the post-translational modification of these histones referred to as histone marks. One of these marks is the methylation of lysine 4 of the core histone H3 (H3K4). While mono-methylation of H3K4 (H3K4me1) is located preferentially at active enhancers, tri-methylation (H3K4me3) is a mark found at open and potentially active promoters. Thus, H3K4 methylation is typically associated with gene transcription. The class 2 lysine methyltransferases (KMTs) are the main enzymes that methylate H3K4. KMT2 enzymes function in complexes that contain a necessary core complex composed of WDR5, RBBP5, ASH2L, and DPY30, the so-called WRAD complex. -
A Family of Mammalian E3 Ubiquitin Ligases That Contain the UBR Box Motif and Recognize N-Degrons Takafumi Tasaki,1 Lubbertus C
MOLECULAR AND CELLULAR BIOLOGY, Aug. 2005, p. 7120–7136 Vol. 25, No. 16 0270-7306/05/$08.00ϩ0 doi:10.1128/MCB.25.16.7120–7136.2005 Copyright © 2005, American Society for Microbiology. All Rights Reserved. A Family of Mammalian E3 Ubiquitin Ligases That Contain the UBR Box Motif and Recognize N-Degrons Takafumi Tasaki,1 Lubbertus C. F. Mulder,2 Akihiro Iwamatsu,3 Min Jae Lee,1 Ilia V. Davydov,4† Alexander Varshavsky,4 Mark Muesing,2 and Yong Tae Kwon1* Center for Pharmacogenetics and Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania 152611; Aaron Diamond AIDS Research Center, The Rockefeller University, New York, New York 100162; Protein Research Network, Inc., Yokohama, Kanagawa 236-0004, Japan3; and Division of Biology, California Institute of Technology, Pasadena, California 911254 Received 15 March 2005/Returned for modification 27 April 2005/Accepted 13 May 2005 A subset of proteins targeted by the N-end rule pathway bear degradation signals called N-degrons, whose determinants include destabilizing N-terminal residues. Our previous work identified mouse UBR1 and UBR2 as E3 ubiquitin ligases that recognize N-degrons. Such E3s are called N-recognins. We report here that while double-mutant UBR1؊/؊ UBR2؊/؊ mice die as early embryos, the rescued UBR1؊/؊ UBR2؊/؊ fibroblasts still retain the N-end rule pathway, albeit of lower activity than that of wild-type fibroblasts. An affinity assay for proteins that bind to destabilizing N-terminal residues has identified, in addition to UBR1 and UBR2, a huge (570 kDa) mouse protein, termed UBR4, and also the 300-kDa UBR5, a previously characterized mammalian E3 known as EDD/hHYD. -
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. -
Datasheet: AHP2440 Product Details
Datasheet: AHP2440 Description: RABBIT ANTI ATG4B Specificity: ATG4B Format: Purified Product Type: Polyclonal Antibody Isotype: Polyclonal IgG Quantity: 50 µl Product Details Applications This product has been reported to work in the following applications. This information is derived from testing within our laboratories, peer-reviewed publications or personal communications from the originators. Please refer to references indicated for further information. For general protocol recommendations, please visit www.bio- rad-antibodies.com/protocols. Yes No Not Determined Suggested Dilution Western Blotting 1/500 - 1/2000 Where this product has not been tested for use in a particular technique this does not necessarily exclude its use in such procedures. Suggested working dilutions are given as a guide only. It is recommended that the user titrates the product for use in their own system using appropriate negative/positive controls. Target Species Human Product Form Purified IgG - liquid Antiserum Preparation Antiserum to ATG4B was raised by repeated immunization of rabbits with highly purified antigen. Purified IgG was prepared from whole serum by affinity chromatography. Buffer Solution Phosphate buffered saline Preservative 0.02% Sodium Azide Stabilisers 50% Glycerol Immunogen Recombinant human ATG4B External Database Links UniProt: Q9Y4P1 Related reagents Entrez Gene: 23192 ATG4B Related reagents Page 1 of 2 Synonyms APG4B, AUTL1, KIAA0943 Specificity Rabbit anti ATG4B antibody recognizes the cysteine protease ATG4B, also known as AUT-like 1 cysteine endopeptidase, autophagin-1, autophagy-related cysteine endopeptidase 1 or autophagy-related protein 4 homolog B. ATG4B is a member of the cysteine protease family. ATG4B plays an important role in autophagosome formation. Western Blotting Rabbit anti ATG4B antibody detects a band of approximately 44 kDa in cell lysates under reducing conditions Storage Store at -20oC Storage in frost-free freezers is not recommended. -
Teleological Role of L-2-Hydroxyglutarate
© 2020. Published by The Company of Biologists Ltd | Disease Models & Mechanisms (2020) 13, dmm045898. doi:10.1242/dmm.045898 RESEARCH ARTICLE Teleological role of L-2-hydroxyglutarate dehydrogenase in the kidney Garrett Brinkley1, Hyeyoung Nam1, Eunhee Shim1,*, Richard Kirkman1, Anirban Kundu1, Suman Karki1, Yasaman Heidarian2, Jason M. Tennessen2, Juan Liu3, Jason W. Locasale3, Tao Guo4, Shi Wei4, Jennifer Gordetsky5, Teresa L. Johnson-Pais6, Devin Absher7, Dinesh Rakheja8, Anil K. Challa9 and Sunil Sudarshan1,10,‡ ABSTRACT insight into the physiological role of L2HGDH as well as mechanisms L-2-hydroxyglutarate (L-2HG) is an oncometabolite found elevated in that promote L-2HG accumulation in disease states. renal tumors. However, this molecule might have physiological roles that extend beyond its association with cancer, as L-2HG levels are KEY WORDS: L-2-hydroxyglutarate, L-2-hydroxyglutarate dehydrogenase, TCA cycle, PPARGC1A elevated in response to hypoxia and during Drosophila larval development. L-2HG is known to be metabolized by L-2HG dehydrogenase (L2HGDH), and loss of L2HGDH leads to elevated INTRODUCTION L-2HG levels. Despite L2HGDH being highly expressed in the kidney, Oncometabolites are small molecules that have been found elevated its role in renal metabolism has not been explored. Here, we report our in various malignancies. To date, these molecules include the findings utilizing a novel CRISPR/Cas9 murine knockout model, with tricarboxylic acid (TCA) cycle intermediates succinate and fumarate a specific focus on the role of L2HGDH in the kidney. Histologically, as well as both enantiomers of 2-hydroxyglutarate (D-2HG and L2hgdh knockout kidneys have no demonstrable histologic L-2HG) (Tomlinson et al., 2002; Baysal et al., 2000; Niemann and abnormalities. -
Chuanxiong Rhizoma Compound on HIF-VEGF Pathway and Cerebral Ischemia-Reperfusion Injury’S Biological Network Based on Systematic Pharmacology
ORIGINAL RESEARCH published: 25 June 2021 doi: 10.3389/fphar.2021.601846 Exploring the Regulatory Mechanism of Hedysarum Multijugum Maxim.-Chuanxiong Rhizoma Compound on HIF-VEGF Pathway and Cerebral Ischemia-Reperfusion Injury’s Biological Network Based on Systematic Pharmacology Kailin Yang 1†, Liuting Zeng 1†, Anqi Ge 2†, Yi Chen 1†, Shanshan Wang 1†, Xiaofei Zhu 1,3† and Jinwen Ge 1,4* Edited by: 1 Takashi Sato, Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of 2 Tokyo University of Pharmacy and Life Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha, China, Galactophore Department, The First 3 Sciences, Japan Hospital of Hunan University of Chinese Medicine, Changsha, China, School of Graduate, Central South University, Changsha, China, 4Shaoyang University, Shaoyang, China Reviewed by: Hui Zhao, Capital Medical University, China Background: Clinical research found that Hedysarum Multijugum Maxim.-Chuanxiong Maria Luisa Del Moral, fi University of Jaén, Spain Rhizoma Compound (HCC) has de nite curative effect on cerebral ischemic diseases, *Correspondence: such as ischemic stroke and cerebral ischemia-reperfusion injury (CIR). However, its Jinwen Ge mechanism for treating cerebral ischemia is still not fully explained. [email protected] †These authors share first authorship Methods: The traditional Chinese medicine related database were utilized to obtain the components of HCC. The Pharmmapper were used to predict HCC’s potential targets. Specialty section: The CIR genes were obtained from Genecards and OMIM and the protein-protein This article was submitted to interaction (PPI) data of HCC’s targets and IS genes were obtained from String Ethnopharmacology, a section of the journal database.