DOCSLIB.ORG

Research 1..8

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Research 1..8 Article pubs.acs.org/jpr Proteome Atlas of Human Chromosome 8 and Its Multiple 8p Deficiencies in Tumorigenesis of the Stomach, Colon, and Liver † ○ † ○ ‡ § ○ ∥ ○ † † † Yang Zhang, , Guoquan Yan, , Linhui Zhai, , , Shaohang Xu, , Huali Shen, Jun Yao, Feifei Wu, † # † † † ‡ § ‡ § Liqi Xie, Hailin Tang, Hongxiu Yu, Mingqi Liu, Pengyuan Yang, Ping Xu, , Chengpu Zhang, , ‡ § ‡ § ‡ § ‡ § ‡ § ∥ ⊥ ∥ Liwei Li, , Cheng Chang, , Ning Li, , Songfeng Wu, , Yunping Zhu, , Quanhui Wang, , Bo Wen, ∥ ∥ ∥ □ † ∥ ⊥ ‡ § Liang Lin, Yinzhu Wang, Guiyan Zheng, Lanping Zhou, Haojie Lu,*, Siqi Liu,*, , Fuchu He,*, , † and Fan Zhong*, † Institutes of Biomedical Sciences and Department of Chemistry, Fudan University, Shanghai 200032, China ‡ State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 102206, China § National Engineering Research Center for Protein Drugs, Beijing 102206, China ∥ BGI-Shenzhen, Shenzhen 518083, China ⊥ Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100029, China # College of Mechanical & Electronic Engineering and Automatization, National University of Defense Technology, Changsha 410073, China □ State Key Laboratory of Molecular Oncology, Cancer Institute & Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China *S Supporting Information ABSTRACT: Chromosome 8, a medium-length euchromatic unit in humans that has an extraordinarily high mutation rate, can be detected not only in evolution but also in multiple mutant diseases, such as tumorigenesis, and further invasion/ metastasis. The Chromosome-Centric Human Proteome Project of China systematically profiles the proteomes of three digestive organs (i.e., stomach, colon, and liver) and their corresponding carcinoma tissues/cell lines according to a chromosome organizational roadmap. By rigorous standards, we have identified 271 (38.7%), 330 (47.1%), and 325 (46.4%) of 701 chromosome 8-coded proteins from stomach, colon, and liver samples, respectively, in Swiss-Prot and observed a total coverage rate of up to 58.9% by 413 identified proteins. Using large-scale label-free proteome quantitation, we also found some 8p deficiencies, such as the presence of 8p21−p23 in tumorigenesis of the above-described digestive organs, which is in good agreement with previous reports. To our best knowledge, this is the first study to have verified these 8p deficiencies at the proteome level, complementing genome and transcriptome data. KEYWORDS: chromosome 8, proteome, 8p deletion, tumorigenesis, liver, colon, stomach ■ INTRODUCTION Chromosome 8 is a medium-length euchromatic unit in humans that has an extraordinarily high mutation rate by The Chromosome-Centric Human Proteome Project (C-HPP) 3,4 5 6,7 fi positive selection. DEF and MCPH1 are widely known has received considerable attention for its signi cance in rapidly evolving gene clusters in 8p. Telomere shortening, understanding gene function and structure in terms of especially in chromosome 8, appears as a mechanism fostering chromosome proteins.1,2 The International Human Genome the development of chromosomal instability during aging and Sequencing Consortium recently completed a sequence of the chronic disease.8 This relatively high genomic instability of human genome including chromosome 8. It has reported a chromosome 8 is found not only in evolution but also in manually curated gene catalog, containing 793 gene loci and 301 pseudogene loci, including all previously known genes on Special Issue: Chromosome-centric Human Proteome Project 3 chromosome 8 and giving 701 nonredundant proteins in Received: August 31, 2012 Swiss-Prot (Version 2012-7-11). © XXXX American Chemical Society A dx.doi.org/10.1021/pr300834r | J. Proteome Res. XXXX, XXX, XXX−XXX Journal of Proteome Research Article Figure 1. Chromosome 8 proteome atlas with data on the quantification (A) and identification (B) of gastric (green text and frame), colorectal (blue text and frame), and hepatic (red text and frame) systems. (A) The colors denote the abundance of the protein expression data. The median − normalized protein data were transformed by log2 and rescaled into a [ 1,1] region. The protein data above the median are shown in red, whereas those below the median are shown in blue. The color legend is provided at the top portion. (B) The protein coding genes are shown in blue. multiple mutant diseases, such as tumorigenesis, and further information, is more robust for LTQ data. More details on invasion/metastasis. Chromosome 8 and its 8p deletion have proteome quantification are provided in the related article. The been studied and determined to be associated with mass spectrum results detected rather high incidences of hepatocellular carcinoma (HCC) metastasis for many years.9 missing values (without identification in some replicates). Use As part of the Chinese C-HPP consortium, chromosomes 1, of each proteomic experimental replicate as input column 8, and 20 have been selected to systematically profile the would disrupt further Gene Set Enrichment Analysis (GSEA) proteomes of three digestive organs, namely, stomach, colon, processing. To solve this problem, we calculated the average of and liver, as well as their corresponding carcinoma tissues/cell SIN or LFQuant values for each sample as representation, rather lines. From the perspective of pathophysiological significance in than deal with each fluctuant experimental replicate in further China and worldwide, digestive cancers, such as gastric cancer analysis. For comparative analysis of liver samples, we further (GC), colorectal cancer (CRC), and HCC, are among the most normalized SIN and LFQuant values by dividing their medians. frequently reported cancers and are characterized by metastatic Biological Category Statistics and Enrichment Analysis potential and poor outcomes. This digestive group includes some of the most critical cancers (among them are those “Data set Files” and “Analyses” under “Human Genes ranked second to fourth in cancer-related mortality) and, Chromosomal Location” in Ingenuity Pathway Analysis (IPA, despite all sustained efforts, maintains a profile of low survival Ingenuity Systems; www.ingenuity.com) Version 14197757 rates and lacks successful therapies.10 Herein, we report the were used for cell, tissue, and organ (CTO) and cell line proteome of chromosome 8 based on measured proteins from distribution statistics as well as biological category enrichment samples of selected digestive tissues/cells and summarize the analysis. total nonredundant proteins reported so far for the said Enrichment analysis of 288 missing chromosome 8-coded proteome. We also discuss the connections of measured 8p proteins was carried out using the web-accessible Database for deletions with these three digestive cancers. Annotation, Visualization, and Integrated Discovery (DAVID) tool.14 DAVID can recognize the UniProt AC from data sets. ■ MATERIALS AND METHODS Medium classification stringency and default items were chosen for enrichment calculation. Proteome Identification and Quantification GSEA Proteomes from 18 samples, namely, liver tissue11 Hep3B, SNU398, SNU449, SNU475, MHCC97L (97L), MHCC97H GSEA15 was performed to find down-regulated enriched (97H), HCCLM3 (LM3), HCCLM6 (LM6), colon tissue, cytobands in chromosome 8. The data set was loaded from CRC tissue, SW480, HCT116, stomach tissue, GC tissue, AGS, HUGO Gene Nomenclature Committee-approved gene BGC823, and SGC7901, were identified or researched as symbols16 and analyzed using the Java GSEA package.17 We described in a companion article (DOI: 10.1021/pr3008286). scanned (Signal2Noise metric, weighted scoring, 1,000 Protein abundance in the human liver data set and that in 17 phenotype permutations) the cytoband-organized c1 gene fi 12 13 other samples were quanti ed by SIN and by LFQuant, sets of Molecular Signature Database v3.0. As GSEA requires respectively. Both are label-free proteome quantification at least three (sample) columns for each phenotype group, we methods, and the SIN method, which does not use XIC replicated stomach, colon, and liver proteome data to appear B dx.doi.org/10.1021/pr300834r | J. Proteome Res. XXXX, XXX, XXX−XXX Journal of Proteome Research Article Figure 2. Overlapping status of samples in total and chromosome 8-coded protein identifications. (A−C) Unique (diagonal, red text) and overlapped identification scales within gastric (A), colorectal (B), and hepatic (C) systems. Numbers of chromosome 8-coded proteins are given in brackets. (D−K) Venn diagrams comparing total proteins (D−F) and chromosome 8-coded proteins (G−I) identified within the three digestive systems and among three normal digestive organs (J, K). (L, M) Venn diagrams comparing total proteins (L) and chromosome 8-coded proteins (M) from the present study, PeptideAtlas, and MaxQB. thrice as well as HCT116 and SW480 proteome data to appear respectively, using rigorous standards. The proteomes from twice for comparison. The gene sets with normalized these samples provided 413 identified proteins in total and gave enrichment scores lower than −1.00 were enriched in a a total coverage of up to 58.9%. The total identification down-regulated direction. coverage of chromosome 8-coded proteins in other 5 databases were Ensembl (gene level, v.69) 402/696 = 57.8%, neXtProt ■ RESULTS (v.2012-10-16) 413/700 = 59.0% (Table S2 in Supporting Information), GPMdb (green, v.2012-10-18) 355/472 = 75.2%, Proteomes of the Three Digestive Organs Peptide Atlas (1% FDR
Load more

Recommended publications
  • SH3 Interactome Conserves General Function Over Specific Form
    SH3 Interactome Conserves General Function Over Specific Form Xiaofeng Xin, David Gfeller, Jackie Cheng, Raffi Tonikian, Lin Sun, Ailan Guo, Lianet Lopez, Alevtina Pavlenco, Adenrele Akintobi, Yingnan Zhang, Jean-Francois Rual, Bridget Currell, Somasekar Seshagiri, Tong Hao, Xinping Yang, Yun A. Shen, Kourosh Salehi-Ashtiani, Jingjing Li, Aaron T. Cheng, Dryden Bouamalay, Adrien Lugari, David E. Hill, Mark L. Grimes, David G. Drubin, Barth D. Grant, Marc Vidal, Charles Boone, Sachdev S. Sidhu, Gary D. Bader. Table of content: 1. Supplementary Information – Data analysis 2. Supplementary Figures 1-13 3. Supplementary Tables 1-19 4. References 1. Supplementary Information Data analysis Domain-protein two-way clustergram The domain-protein two-way clustergram in Supplementary Figure 5 was generated as previously described (Jin et al, 2009), with some modifications. In particular, similarities were computed between protein-domain profiles (defined by the set of domains on each protein) and domain-protein profiles (defined by the set of proteins for each domain) using the Jaccard similarity coefficient (size of the intersection divided by the size of the union of the sets). Domain annotation was obtained from SMART (Letunic et al, 2009; Schultz et al, 2000). This yielded statistical descriptions of the relatedness of any two proteins, based on their domain compositions, and of the relationship between any two domains based on their co-occurrence among proteins. Complete linkage hierarchical clustering was then used to cluster rows and columns of the matrix and produce a two-way clustergram of the yeast and worm SH3 protein sets. The clustergrams were generated using the MATLAB Bioinformatics Toolbox.
    [Show full text]
  • Genetic Basis of Simple and Complex Traits with Relevance to Avian Evolution
    Genetic basis of simple and complex traits with relevance to avian evolution Małgorzata Anna Gazda Doctoral Program in Biodiversity, Genetics and Evolution D Faculdade de Ciências da Universidade do Porto 2019 Supervisor Miguel Jorge Pinto Carneiro, Auxiliary Researcher, CIBIO/InBIO, Laboratório Associado, Universidade do Porto Co-supervisor Ricardo Lopes, CIBIO/InBIO Leif Andersson, Uppsala University FCUP Genetic basis of avian traits Nota Previa Na elaboração desta tese, e nos termos do número 2 do Artigo 4º do Regulamento Geral dos Terceiros Ciclos de Estudos da Universidade do Porto e do Artigo 31º do D.L.74/2006, de 24 de Março, com a nova redação introduzida pelo D.L. 230/2009, de 14 de Setembro, foi efetuado o aproveitamento total de um conjunto coerente de trabalhos de investigação já publicados ou submetidos para publicação em revistas internacionais indexadas e com arbitragem científica, os quais integram alguns dos capítulos da presente tese. Tendo em conta que os referidos trabalhos foram realizados com a colaboração de outros autores, o candidato esclarece que, em todos eles, participou ativamente na sua conceção, na obtenção, análise e discussão de resultados, bem como na elaboração da sua forma publicada. Este trabalho foi apoiado pela Fundação para a Ciência e Tecnologia (FCT) através da atribuição de uma bolsa de doutoramento (PD/BD/114042/2015) no âmbito do programa doutoral em Biodiversidade, Genética e Evolução (BIODIV). 2 FCUP Genetic basis of avian traits Acknowledgements Firstly, I would like to thank to my all supervisors Miguel Carneiro, Ricardo Lopes and Leif Andersson, for the demanding task of supervising myself last four years.
    [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]
  • Noelia Díaz Blanco
    Effects of environmental factors on the gonadal transcriptome of European sea bass (Dicentrarchus labrax), juvenile growth and sex ratios Noelia Díaz Blanco Ph.D. thesis 2014 Submitted in partial fulfillment of the requirements for the Ph.D. degree from the Universitat Pompeu Fabra (UPF). This work has been carried out at the Group of Biology of Reproduction (GBR), at the Department of Renewable Marine Resources of the Institute of Marine Sciences (ICM-CSIC). Thesis supervisor: Dr. Francesc Piferrer Professor d’Investigació Institut de Ciències del Mar (ICM-CSIC) i ii A mis padres A Xavi iii iv Acknowledgements This thesis has been made possible by the support of many people who in one way or another, many times unknowingly, gave me the strength to overcome this "long and winding road". First of all, I would like to thank my supervisor, Dr. Francesc Piferrer, for his patience, guidance and wise advice throughout all this Ph.D. experience. But above all, for the trust he placed on me almost seven years ago when he offered me the opportunity to be part of his team. Thanks also for teaching me how to question always everything, for sharing with me your enthusiasm for science and for giving me the opportunity of learning from you by participating in many projects, collaborations and scientific meetings. I am also thankful to my colleagues (former and present Group of Biology of Reproduction members) for your support and encouragement throughout this journey. To the “exGBRs”, thanks for helping me with my first steps into this world. Working as an undergrad with you Dr.
    [Show full text]
  • Cellular and Molecular Investigations of Undiagnosed Neurometabolic
    CELLULAR AND MOLECULAR INVESTIGATIONS OF UNDIAGNOSED NEUROMETABOLIC DISORDERS Submitted in application for award of Doctor of Philosophy (PhD) Emma Reid Centre for Translational Omics Genetics and Genomic Medicine Institute of Child Health University College London August 2016 DECLARATION I, Emma Reid, confirm that the work presented in this thesis is my own. Where information has been derived from other sources, I confirm that this has been indicated in the thesis. Where experimental or analytical work has been completed by others, this has been stated in the relevant section of this thesis. However, these instances are also listed below: • Alignment of sequencing reads to the reference genome, variant calling (Section 2.4.11) and ExomeDepth analysis (Section 3.3.3) of the gene panel sequencing data was performed by Dr Chris Boustred (NE Thames Regional Genetics Service, GOSH, UK). • Whole exome sequencing of patients X, 1, 4 and 5 was outsourced to BGI Genomics Hong Kong and the resulting raw data files were processed and aligned by Dr Chela James (GOSgene, ICH, UK) (Section 2.5). • Whole exome sequencing of patient Y and processing of the resulting raw data was performed by Dr Olaf Bodamer (University of Miami, USA) (Section 6.4.1). • Homozygosity mapping and whole exome sequencing of index PROSC family was performed by Dr Niklas Darin (The Queen Silvia Children’s Hospital, Sweden) (Section 7.1.4). • Sanger sequencing of additional PROSC and PNPO-deficient patients was performed by Dr Philippa Mills (ICH, UK) (Section 7.2). • Sample processing for electron microscopy analysis was carried out by Elizabeth Latimer- Bowman (Histopathology Department, GOSH, UK) and imaging was performed by Glenn Anderson (Histopathology Department, GOSH, UK) (Section 2.14.2).
    [Show full text]
  • Early Growth Response 1 Regulates Hematopoietic Support and Proliferation in Human Primary Bone Marrow Stromal Cells
    Hematopoiesis SUPPLEMENTARY APPENDIX Early growth response 1 regulates hematopoietic support and proliferation in human primary bone marrow stromal cells Hongzhe Li, 1,2 Hooi-Ching Lim, 1,2 Dimitra Zacharaki, 1,2 Xiaojie Xian, 2,3 Keane J.G. Kenswil, 4 Sandro Bräunig, 1,2 Marc H.G.P. Raaijmakers, 4 Niels-Bjarne Woods, 2,3 Jenny Hansson, 1,2 and Stefan Scheding 1,2,5 1Division of Molecular Hematology, Department of Laboratory Medicine, Lund University, Lund, Sweden; 2Lund Stem Cell Center, Depart - ment of Laboratory Medicine, Lund University, Lund, Sweden; 3Division of Molecular Medicine and Gene Therapy, Department of Labora - tory Medicine, Lund University, Lund, Sweden; 4Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands and 5Department of Hematology, Skåne University Hospital Lund, Skåne, Sweden ©2020 Ferrata Storti Foundation. This is an open-access paper. doi:10.3324/haematol. 2019.216648 Received: January 14, 2019. Accepted: July 19, 2019. Pre-published: August 1, 2019. Correspondence: STEFAN SCHEDING - [email protected] Li et al.: Supplemental data 1. Supplemental Materials and Methods BM-MNC isolation Bone marrow mononuclear cells (BM-MNC) from BM aspiration samples were isolated by density gradient centrifugation (LSM 1077 Lymphocyte, PAA, Pasching, Austria) either with or without prior incubation with RosetteSep Human Mesenchymal Stem Cell Enrichment Cocktail (STEMCELL Technologies, Vancouver, Canada) for lineage depletion (CD3, CD14, CD19, CD38, CD66b, glycophorin A). BM-MNCs from fetal long bones and adult hip bones were isolated as reported previously 1 by gently crushing bones (femora, tibiae, fibulae, humeri, radii and ulna) in PBS+0.5% FCS subsequent passing of the cell suspension through a 40-µm filter.
    [Show full text]
  • The Landscape of Human Mutually Exclusive Splicing
    bioRxiv preprint doi: https://doi.org/10.1101/133215; this version posted May 2, 2017. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-ND 4.0 International license. The landscape of human mutually exclusive splicing Klas Hatje1,2,#,*, Ramon O. Vidal2,*, Raza-Ur Rahman2, Dominic Simm1,3, Björn Hammesfahr1,$, Orr Shomroni2, Stefan Bonn2§ & Martin Kollmar1§ 1 Group of Systems Biology of Motor Proteins, Department of NMR-based Structural Biology, Max-Planck-Institute for Biophysical Chemistry, Göttingen, Germany 2 Group of Computational Systems Biology, German Center for Neurodegenerative Diseases, Göttingen, Germany 3 Theoretical Computer Science and Algorithmic Methods, Institute of Computer Science, Georg-August-University Göttingen, Germany § Corresponding authors # Current address: Roche Pharmaceutical Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland $ Current address: Research and Development - Data Management (RD-DM), KWS SAAT SE, Einbeck, Germany * These authors contributed equally E-mail addresses: KH: [email protected], RV: [email protected], RR: [email protected], DS: [email protected], BH: [email protected], OS: [email protected], SB: [email protected], MK: [email protected] - 1 - bioRxiv preprint doi: https://doi.org/10.1101/133215; this version posted May 2, 2017. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.
    [Show full text]
  • Role and Regulation of the P53-Homolog P73 in the Transformation of Normal Human Fibroblasts
    Role and regulation of the p53-homolog p73 in the transformation of normal human fibroblasts Dissertation zur Erlangung des naturwissenschaftlichen Doktorgrades der Bayerischen Julius-Maximilians-Universität Würzburg vorgelegt von Lars Hofmann aus Aschaffenburg Würzburg 2007 Eingereicht am Mitglieder der Promotionskommission: Vorsitzender: Prof. Dr. Dr. Martin J. Müller Gutachter: Prof. Dr. Michael P. Schön Gutachter : Prof. Dr. Georg Krohne Tag des Promotionskolloquiums: Doktorurkunde ausgehändigt am Erklärung Hiermit erkläre ich, dass ich die vorliegende Arbeit selbständig angefertigt und keine anderen als die angegebenen Hilfsmittel und Quellen verwendet habe. Diese Arbeit wurde weder in gleicher noch in ähnlicher Form in einem anderen Prüfungsverfahren vorgelegt. Ich habe früher, außer den mit dem Zulassungsgesuch urkundlichen Graden, keine weiteren akademischen Grade erworben und zu erwerben gesucht. Würzburg, Lars Hofmann Content SUMMARY ................................................................................................................ IV ZUSAMMENFASSUNG ............................................................................................. V 1. INTRODUCTION ................................................................................................. 1 1.1. Molecular basics of cancer .......................................................................................... 1 1.2. Early research on tumorigenesis ................................................................................. 3 1.3. Developing
    [Show full text]
  • Vinexin Family (SORBS) Proteins Play Different Roles in Stiffness- Sensing and Contractile Force Generation Takafumi Ichikawa1,2, Masahiro Kita1, Tsubasa S
    © 2017. Published by The Company of Biologists Ltd | Journal of Cell Science (2017) 130, 3517-3531 doi:10.1242/jcs.200691 RESEARCH ARTICLE Vinexin family (SORBS) proteins play different roles in stiffness- sensing and contractile force generation Takafumi Ichikawa1,2, Masahiro Kita1, Tsubasa S. Matsui3,4, Ayaka Ichikawa Nagasato1, Tomohiko Araki3, Shian-Huey Chiang5, Takuhito Sezaki1, Yasuhisa Kimura1, Kazumitsu Ueda1,2, Shinji Deguchi3,4, Alan R. Saltiel5,* and Noriyuki Kioka1,2,‡ ABSTRACT generating actin stress fibers (SFs) (Geiger et al., 2001). This Vinexin, c-Cbl associated protein (CAP) and Arg-binding protein 2 ‘ ’ (ArgBP2) constitute an adaptor protein family called the vinexin mechanical linkage acts as a molecular clutch to transmit the force (SORBS) family that is targeted to focal adhesions (FAs). Although derived from non-muscle myosin-II-dependent contraction to the numerous studies have focused on each of the SORBS proteins and ECM. Cells on more rigid substrates exert greater contractile forces partially elucidated their involvement in mechanotransduction, a than those on soft substrates (Hoffman et al., 2011; Roca-Cusachs comparative analysis of their function has not been well addressed. et al., 2012; LaCroix et al., 2015). These alterations can lead to Here, we established mouse embryonic fibroblasts that individually stiffness-dependent biochemical signals. Among the numerous FA scaffolding proteins, vinculin is one of expressed SORBS proteins and analysed their functions in an ‘ ’ identical cell context. Both vinexin-α and CAP co-localized with the main clutch molecules that can regulate force transmission. vinculin at FAs and promoted the appearance of vinculin-rich FAs, Vinculin consists of an N-terminal head region and a C-terminal tail α region separated by a flexible proline-rich linker region (Bakolitsa whereas ArgBP2 co-localized with -actinin at the proximal end of – FAs and punctate structures on actin stress fibers (SFs), and induced et al., 2004; Borgon et al., 2004).
    [Show full text]
  • Cyclin a Triggers Mitosis Either Via Greatwall Or Cyclin B
    bioRxiv preprint doi: https://doi.org/10.1101/501684; this version posted December 20, 2018. 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. Cyclin A triggers Mitosis either via Greatwall or Cyclin B Nadia Hégarat(1)*, Adrijana Crncec(1)*, Maria F. Suarez Peredoa Rodri- guez(1), Fabio Echegaray Iturra(1), Yan Gu(1), Paul F. Lang(2), Alexis R. Barr(3), Chris Bakal(4), Masato T. Kanemaki(5), Angus I. Lamond(6), Bela Novak(2), Tony Ly(7)•• and Helfrid Hochegger(1)•• (1) Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Brighton BN19RQ, UK (2) Department of Biochemistry, University of Oxford, South Park Road, Oxford OX13QU, UK (3) MRC London Institute of Medical Science, Imperial College, London W12 0NN, UK (4) The Institute of Cancer Research, London SW3 6JB, UK (5) National Institute of Genetics, Research Organization of Information and Sys- tems (ROIS), and Department of Genetics, SOKENDAI (The Graduate University of Advanced Studies), Yata 1111, Mishima, Shizuoka 411-8540, Japan. (6) Centre for Gene Regulation and Expression, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK (7) Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh EH9 3BF, UK * Equal contribution ** Correspondence: Tony Ly: [email protected]; Helfrid Hochegger: [email protected] bioRxiv preprint doi: https://doi.org/10.1101/501684; this version posted December 20, 2018.
    [Show full text]
  • Datasheet: VMA00460 Product Details
    Datasheet: VMA00460 Description: MOUSE ANTI PROSC Specificity: PROSC Format: Purified Product Type: PrecisionAb™ Monoclonal Clone: 3A6 Isotype: IgG1 Quantity: 100 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 1/1000 PrecisionAb antibodies have been extensively validated for the western blot application. The antibody has been validated at the suggested dilution. Where this product has not been tested for use in a particular technique this does not necessarily exclude its use in such procedures. Further optimization may be required dependant on sample type. Target Species Human Species Cross Reacts with: Mouse Reactivity N.B. Antibody reactivity and working conditions may vary between species. Product Form Purified IgG - liquid Preparation Purified IgG prepared by affinity chromatography on Protein G from ascites Buffer Solution Phosphate buffered saline Preservative 0.09% Sodium Azide (NaN3) Stabilisers 1% Bovine Serum Albumin 50% Glycerol Immunogen Full length recombinant protein of human PROSC produced in E. Coli. External Database Links UniProt: O94903 Related reagents Entrez Gene: 11212 PROSC Related reagents Page 1 of 2 Specificity Mouse anti Human PROSC antibody recognizes PROSC also known as proline synthase co-transcribed bacterial homolog protein. PROSC is a ubiquitoously expressed 275 amino acid cytoplasmic protein highly conserved between divergent species (Ikegawa 1999). Mouse anti Human PROSC antibody detects a band of 30 kDa.
    [Show full text]
  • Based on Network Pharmacology and RNA Sequencing Techniques to Explore the Molecular Mechanism of Huatan Jiangzhuo Decoction for Treating Hyperlipidemia
    Hindawi Evidence-Based Complementary and Alternative Medicine Volume 2021, Article ID 9863714, 16 pages https://doi.org/10.1155/2021/9863714 Research Article Based on Network Pharmacology and RNA Sequencing Techniques to Explore the Molecular Mechanism of Huatan Jiangzhuo Decoction for Treating Hyperlipidemia XiaowenZhou ,1 ZhenqianYan ,1 YaxinWang ,1 QiRen ,1 XiaoqiLiu ,2 GeFang ,3 Bin Wang ,4 and Xiantao Li 1 1Laboratory of TCM Syndrome Essence and Objectification, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China 2Guangzhou Sagene Tech Co., Ltd., Guangzhou 510006, China 3College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha 410208, China 4Shenzhen Traditional Chinese Medicine Hospital, Shenzhen 518000, China Correspondence should be addressed to Xiantao Li; [email protected] Received 22 May 2020; Revised 12 March 2021; Accepted 18 March 2021; Published 12 April 2021 Academic Editor: Jianbo Wan Copyright © 2021 Xiaowen Zhou et al. +is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background. Hyperlipidemia, due to the practice of unhealthy lifestyles of modern people, has been a disturbance to a large portion of population worldwide. Recently, several scholars have turned their attention to Chinese medicine (CM) to seek out a lipid-lowering approach with high efficiency and low toxicity. +is study aimed to explore the mechanism of Huatan Jiangzhuo decoction (HTJZD, a prescription of CM) in the treatment of hyperlipidemia and to determine the major regulation pathways and potential key targets involved in the treatment process.
    [Show full text]