Genetic Variations Associated with Resistance to Doxorubicin and Paclitaxel in Breast Cancer
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Dysfunctional Mechanotransduction Through the YAP/TAZ/Hippo Pathway As a Feature of Chronic Disease
cells Review Dysfunctional Mechanotransduction through the YAP/TAZ/Hippo Pathway as a Feature of Chronic Disease 1, 2, 2,3, 4 Mathias Cobbaut y, Simge Karagil y, Lucrezia Bruno y, Maria Del Carmen Diaz de la Loza , Francesca E Mackenzie 3, Michael Stolinski 2 and Ahmed Elbediwy 2,* 1 Protein Phosphorylation Lab, Francis Crick Institute, London NW1 1AT, UK; [email protected] 2 Department of Biomolecular Sciences, Kingston University, Kingston-upon-Thames KT1 2EE, UK; [email protected] (S.K.); [email protected] (L.B.); [email protected] (M.S.) 3 Department of Chemical and Pharmaceutical Sciences, Kingston University, Kingston-upon-Thames KT1 2EE, UK; [email protected] 4 Epithelial Biology Lab, Francis Crick Institute, London NW1 1AT, UK; [email protected] * Correspondence: [email protected] These authors contribute equally to this work. y Received: 30 November 2019; Accepted: 4 January 2020; Published: 8 January 2020 Abstract: In order to ascertain their external environment, cells and tissues have the capability to sense and process a variety of stresses, including stretching and compression forces. These mechanical forces, as experienced by cells and tissues, are then converted into biochemical signals within the cell, leading to a number of cellular mechanisms being activated, including proliferation, differentiation and migration. If the conversion of mechanical cues into biochemical signals is perturbed in any way, then this can be potentially implicated in chronic disease development and processes such as neurological disorders, cancer and obesity. This review will focus on how the interplay between mechanotransduction, cellular structure, metabolism and signalling cascades led by the Hippo-YAP/TAZ axis can lead to a number of chronic diseases and suggest how we can target various pathways in order to design therapeutic targets for these debilitating diseases and conditions. -
Targeting the Hippo Pathway in Prostate Cancer: What's New?
cancers Review Targeting the Hippo Pathway in Prostate Cancer: What’s New? Kelly Coffey Solid Tumour Target Discovery Laboratory, Translational and Clinical Research Institute, Newcastle University Centre for Cancer, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK; [email protected] Simple Summary: Prostate cancer is the most commonly diagnosed cancer in men in the UK, accounting for the deaths of over 11,000 men per year. A major problem in this disease are tumours which no longer respond to available treatments. Understanding how this occurs will reveal new ways to treat these patients. In this review, the latest findings regarding a particular group of cellular factors which make up a signalling network called the Hippo pathway will be described. Accumulating evidence suggests that this network contributes to prostate cancer progression and resistance to current treatments. Identifying how this pathway can be targeted with drugs is a promising area of research to improve the treatment of prostate cancer. Abstract: Identifying novel therapeutic targets for the treatment of prostate cancer (PC) remains a key area of research. With the emergence of resistance to androgen receptor (AR)-targeting therapies, other signalling pathways which crosstalk with AR signalling are important. Over recent years, evidence has accumulated for targeting the Hippo signalling pathway. Discovered in Drosophila melanogasta, the Hippo pathway plays a role in the regulation of organ size, proliferation, migration and invasion. In response to a variety of stimuli, including cell–cell contact, nutrients and stress, a kinase cascade is activated, which includes STK4/3 and LATS1/2 to inhibit the effector proteins YAP and its paralogue TAZ. -
ZRF1-‐Mediated Transcriptional Regulation in Acute Myeloid Leukemia
ZRF1-mediated transcriptional regulation in acute myeloid leukemia Santiago Demajo Meseguer TESI DOCTORAL UPF / 2013 Aquesta tesi ha estat realitzada sota la direcció del Dr. Luciano Di Croce Departament de Regulació Gènica, Cèl·lules Mare i Càncer Centre de Regulació Genòmica (CRG) Barcelona, desembre de 2013 TABLE OF CONTENTS ABSTRACT ....................................................................................................... 5 INTRODUCTION ...........................................................................................11 1. ACUTE MYELOID LEUKEMIA................................................................................13 1.1 Leukemia ........................................................................................................ 13 1.2 Acute myeloid leukemia (AML)............................................................. 14 1.3 Differentiation therapy in AML............................................................. 15 2. RETINOIC ACID SIGNALING PATHWAY ..............................................................19 2.1 RA metabolism and signaling................................................................ 19 2.2 Role of RA in differentiation, apoptosis and proliferation........ 20 2.3 RA molecular mechanism........................................................................ 22 2.4 Disruption of RA signaling: the example of PML-RARα.............. 23 3. CHROMATIN AND EPIGENETICS IN TRANSCRIPTION ......................................27 3.1 Chromatin structure................................................................................. -
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 -
The Hippo–YAP Pathway in Organ Size Control and Tumorigenesis: an Updated Version
Downloaded from genesdev.cshlp.org on September 26, 2021 - Published by Cold Spring Harbor Laboratory Press REVIEW The Hippo–YAP pathway in organ size control and tumorigenesis: an updated version Bin Zhao,1 Li Li,1 Qunying Lei,2 and Kun-Liang Guan1,3 1Department of Pharmacology and Moores Cancer Center, University of California at San Diego, La Jolla, California 92093, USA; 2Department of Biological Chemistry, School of Medicine, and Molecular and Cell Biology Laboratory, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China The Hippo signaling pathway is gaining recognition as The Hippo pathway was named after the Drosophila an important player in both organ size control and Hippo kinase that was discovered using this approach. tumorigenesis, which are physiological and pathological Components of the Hippo pathway are highly conserved processes that share common cellular signaling mecha- in mammals (Fig. 1). Later genetic and biochemical studies nisms. Upon activation by stimuli such as high cell den- gradually shaped the current working model, in which the sity in cell culture, the Hippo pathway kinase cascade mammalian Mst1/2 kinase (Hippo homolog), complexed phosphorylates and inhibits the Yes-associated protein with a scaffold protein, Sav1, phosphorylates and activates (YAP)/TAZ transcription coactivators representing the the Lats1/2 kinase. Lats1/2 is also activated by another major signaling output of the pathway. Altered gene scaffold protein, Mob1 (Fig. 2). These four proteins are expression resulting from YAP/TAZ inhibition affects often referred to as the core components of the Hippo cell number by repressing cell proliferation and promot- pathway. At the upstream, several components have ing apoptosis, thereby limiting organ size. -
DNAJC2 Rabbit Pab
Leader in Biomolecular Solutions for Life Science DNAJC2 Rabbit pAb Catalog No.: A4633 Basic Information Background Catalog No. This gene is a member of the M-phase phosphoprotein (MPP) family. The gene encodes A4633 a phosphoprotein with a J domain and a Myb DNA-binding domain which localizes to both the nucleus and the cytosol. The protein is capable of forming a heterodimeric Observed MW complex that associates with ribosomes, acting as a molecular chaperone for nascent 72kDa polypeptide chains as they exit the ribosome. This protein was identified as a leukemia- associated antigen and expression of the gene is upregulated in leukemic blasts. Also, Calculated MW chromosomal aberrations involving this gene are associated with primary head and 65kDa/71kDa neck squamous cell tumors. This gene has a pseudogene on chromosome 6. Alternatively spliced variants which encode different protein isoforms have been Category described. Primary antibody Applications WB Cross-Reactivity Human, Mouse Recommended Dilutions Immunogen Information WB 1:500 - 1:2000 Gene ID Swiss Prot 27000 Q99543 Immunogen Recombinant fusion protein containing a sequence corresponding to amino acids 1-140 of human DNAJC2 (NP_055192.1). Synonyms DNAJC2;MPHOSPH11;MPP11;ZRF1;ZUO1 Contact Product Information www.abclonal.com Source Isotype Purification Rabbit IgG Affinity purification Storage Store at -20℃. Avoid freeze / thaw cycles. Buffer: PBS with 0.02% sodium azide,50% glycerol,pH7.3. Validation Data Western blot analysis of extracts of various cell lines, using DNAJC2 antibody (A4633) at 1:1000 dilution. Secondary antibody: HRP Goat Anti-Rabbit IgG (H+L) (AS014) at 1:10000 dilution. Lysates/proteins: 25ug per lane. -
A Causal Gene Network with Genetic Variations Incorporating Biological Knowledge and Latent Variables
A CAUSAL GENE NETWORK WITH GENETIC VARIATIONS INCORPORATING BIOLOGICAL KNOWLEDGE AND LATENT VARIABLES By Jee Young Moon A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy (Statistics) at the UNIVERSITY OF WISCONSIN–MADISON 2013 Date of final oral examination: 12/21/2012 The dissertation is approved by the following members of the Final Oral Committee: Brian S. Yandell. Professor, Statistics, Horticulture Alan D. Attie. Professor, Biochemistry Karl W. Broman. Professor, Biostatistics and Medical Informatics Christina Kendziorski. Associate Professor, Biostatistics and Medical Informatics Sushmita Roy. Assistant Professor, Biostatistics and Medical Informatics, Computer Science, Systems Biology in Wisconsin Institute of Discovery (WID) i To my parents and brother, ii ACKNOWLEDGMENTS I greatly appreciate my adviser, Prof. Brian S. Yandell, who has always encouraged, inspired and supported me. I am grateful to him for introducing me to the exciting research areas of statis- tical genetics and causal gene network analysis. He also allowed me to explore various statistical and biological problems on my own and guided me to see the problems in a bigger picture. Most importantly, he waited patiently as I progressed at my own pace. I would also like to thank Dr. Elias Chaibub Neto and Prof. Xinwei Deng who my adviser arranged for me to work together. These three improved my rigorous writing and thinking a lot when we prepared the second chapter of this dissertation for publication. It was such a nice opportunity for me to join the group of Prof. Alan D. Attie, Dr. Mark P. Keller, Prof. Karl W. Broman and Prof. -
Genetic Insight Into the Domain Structure and Functions of Dicer-Type Ribonucleases
International Journal of Molecular Sciences Review Genetic Insight into the Domain Structure and Functions of Dicer-Type Ribonucleases Kinga Ciechanowska, Maria Pokornowska and Anna Kurzy ´nska-Kokorniak* Department of Ribonucleoprotein Biochemistry, Institute of Bioorganic Chemistry Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznan, Poland; [email protected] (K.C.); [email protected] (M.P.) * Correspondence: [email protected]; Tel.: +48-61-852-85-03 (ext. 1264) Abstract: Ribonuclease Dicer belongs to the family of RNase III endoribonucleases, the enzymes that specifically hydrolyze phosphodiester bonds found in double-stranded regions of RNAs. Dicer enzymes are mostly known for their essential role in the biogenesis of small regulatory RNAs. A typical Dicer-type RNase consists of a helicase domain, a domain of unknown function (DUF283), a PAZ (Piwi-Argonaute-Zwille) domain, two RNase III domains, and a double-stranded RNA binding domain; however, the domain composition of Dicers varies among species. Dicer and its homologues developed only in eukaryotes; nevertheless, the two enzymatic domains of Dicer, helicase and RNase III, display high sequence similarity to their prokaryotic orthologs. Evolutionary studies indicate that a combination of the helicase and RNase III domains in a single protein is a eukaryotic signature and is supposed to be one of the critical events that triggered the consolidation of the eukaryotic RNA interference. In this review, we provide the genetic insight into the domain organization and structure of Dicer proteins found in vertebrate and invertebrate animals, plants and fungi. We also discuss, in the context of the individual domains, domain deletion variants and partner proteins, a variety of Dicers’ functions not only related to small RNA biogenesis pathways. -
[KO Validated] DNAJC2 Rabbit Pab
Leader in Biomolecular Solutions for Life Science [KO Validated] DNAJC2 Rabbit pAb Catalog No.: A19954 KO Validated Basic Information Background Catalog No. This gene is a member of the M-phase phosphoprotein (MPP) family. The gene encodes A19954 a phosphoprotein with a J domain and a Myb DNA-binding domain which localizes to both the nucleus and the cytosol. The protein is capable of forming a heterodimeric Observed MW complex that associates with ribosomes, acting as a molecular chaperone for nascent 80KDa polypeptide chains as they exit the ribosome. This protein was identified as a leukemia- associated antigen and expression of the gene is upregulated in leukemic blasts. Also, Calculated MW chromosomal aberrations involving this gene are associated with primary head and 65kDa/71kDa neck squamous cell tumors. This gene has a pseudogene on chromosome 6. Alternatively spliced variants which encode different protein isoforms have been Category described. Primary antibody Applications WB Cross-Reactivity Human, Mouse Recommended Dilutions Immunogen Information WB 1:500 - 1:2000 Gene ID Swiss Prot 27000 Q99543 Immunogen Recombinant protein of human DNAJC2. Synonyms DNAJC2;MPHOSPH11;MPP11;ZRF1;ZUO1 Contact Product Information www.abclonal.com Source Isotype Purification Rabbit IgG Affinity purification Storage Store at -20℃. Avoid freeze / thaw cycles. Buffer: PBS with 0.02% sodium azide,50% glycerol,pH7.3. Validation Data Western blot analysis of extracts from normal (control) and DNAJC2 knockout (KO) 293T cells, using DNAJC2 antibody (A19954) at 1:1000 dilution. Secondary antibody: HRP Goat Anti-Rabbit IgG (H+L) (AS014) at 1:10000 dilution. Lysates/proteins: 25ug per lane. Blocking buffer: 3% nonfat dry milk in TBST. -
Nucleotide Excision Repair: Interplay Between Nuclear Compartmentalization, Histone Modifications and Signaling
Nucleotide Excision Repair: Interplay between nuclear compartmentalization, histone modifications and signaling Dissertation zur Erlangung des Grades "Doktor der Naturwissenschaften" am Fachbereich Biologie der Johannes Gutenberg-Universität in Mainz Shalaka Chitale geb. am 20.06.1988 in Pune, India Mainz, 2017 Tag der mündlichen Prüfung: 20.06.2017 1 1 Table of Contents SUMMARY 4 ZUSSAMENFASSUNG 5 INTRODUCTION 7 THE NEED FOR EFFICIENT DNA REPAIR: 7 TYPES OF DNA DAMAGE: 7 Double strand break repair 9 Mismatch repair 10 Base excision repair 11 Nucleotide excision repair 12 DNA REPAIR IN THE CONTEXT OF CHROMATIN 17 Mechanisms of regulation of chromatin structure at site of DNA damage 18 Histone modifications: 19 ATP dependent Chromatin remodeling 22 SPATIAL NUCLEAR ORGANIZATION OF NER 23 REFERENCES 26 AIMS OF THE STUDY 34 ZRF1 MEDIATES REMODELING OF E3 LIGASES AT DNA LESION SITES DURING NUCLEOTIDE EXCISION REPAIR 35 INTRODUCTION 36 RESULTS 38 DISCUSSION 52 MATERIALS AND METHODS 57 AUTHOR CONTRIBUTION 63 REFERENCES 63 NUCLEAR ORGANIZATION OF NUCLEOTIDE EXCISION REPAIR IS MEDIATED BY RING1B DEPENDENT H2A-UBIQUITYLATION 69 SUMMARY 70 INTRODUCTION 70 RESULTS 72 NER is partially routed to the nucleolus and involves reorganization of chromatin 72 DDB2 causes repositioning of chromatin to the vicinity of the nucleolus 77 Nucleolar repositioning requires presence of a functional UV-RING1B complex and H2A-K119 ubiquitylation 80 ZRF1 is present in the nucleolus and facilitates relocalization of chromatin 85 DISCUSSION 88 EXPERIMENTAL PROCEDURES 90 -
An Integrative Analysis of Gene Expression Profiles
Int J Clin Exp Pathol 2020;13(7):1698-1706 www.ijcep.com /ISSN:1936-2625/IJCEP0107763 Original Article Identification of transcriptomic markers for developing idiopathic pulmonary fibrosis: an integrative analysis of gene expression profiles Diandian Li1, Yi Liu2, Bo Wang1 1Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu 610041, China; 2West China School of Medicine, Sichuan University, Chengdu 610041, China Received January 12, 2020; Accepted March 6, 2020; Epub July 1, 2020; Published July 15, 2020 Abstract: Idiopathic pulmonary fibrosis (IPF) remains a lethal disease with unknown etiology and unmet medical need. The aim of this study was to perform an integrative analysis of multiple public microarray datasets to inves- tigate gene expression patterns between IPF patients and healthy controls. Moreover, functional interpretation of differentially expressed genes (DEGs) was performed to assess the molecular mechanisms underlying IPF progres- sion. DEGs between IPF and normal lung tissues were picked out by GEO2R tool and Venn diagram software. Data- base for Annotation, Visualization and Integrated Discovery (DAVID) was applied to analyze gene ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway. Protein-protein interaction (PPI) of these DEGs was visu- alized by Cytoscape with Search Tool for the Retrieval of Interacting Genes (STRING). 5520 DEGs were identified in IPF based on six profile datasets, including 3714 up-regulated genes and 1806 down-regulated genes. Using Venn software, a total of 367 commonly altered DEGs were revealed, including 259 up-regulated genes mostly enriched in collagen catabolic process, heparin binding, and the extracellular region. -
Variation in Protein Coding Genes Identifies Information Flow
bioRxiv preprint doi: https://doi.org/10.1101/679456; this version posted June 21, 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. Animal complexity and information flow 1 1 2 3 4 5 Variation in protein coding genes identifies information flow as a contributor to 6 animal complexity 7 8 Jack Dean, Daniela Lopes Cardoso and Colin Sharpe* 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 Institute of Biological and Biomedical Sciences 25 School of Biological Science 26 University of Portsmouth, 27 Portsmouth, UK 28 PO16 7YH 29 30 * Author for correspondence 31 [email protected] 32 33 Orcid numbers: 34 DLC: 0000-0003-2683-1745 35 CS: 0000-0002-5022-0840 36 37 38 39 40 41 42 43 44 45 46 47 48 49 Abstract bioRxiv preprint doi: https://doi.org/10.1101/679456; this version posted June 21, 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. Animal complexity and information flow 2 1 Across the metazoans there is a trend towards greater organismal complexity. How 2 complexity is generated, however, is uncertain. Since C.elegans and humans have 3 approximately the same number of genes, the explanation will depend on how genes are 4 used, rather than their absolute number.