Wilms' Tumour 1 (WT1) in Development, Homeostasis and Disease
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The Splicing Factor U2AF1 Contributes to Cancer Progression Through a Noncanonical Role in Translation Regulation
Downloaded from genesdev.cshlp.org on September 30, 2021 - Published by Cold Spring Harbor Laboratory Press The splicing factor U2AF1 contributes to cancer progression through a noncanonical role in translation regulation Murali Palangat,1 Dimitrios G. Anastasakis,2 Dennis Liang Fei,3 Katherine E. Lindblad,4 Robert Bradley,5 Christopher S. Hourigan,4 Markus Hafner,2 and Daniel R. Larson1 1Laboratory of Receptor Biology and Gene Expression, National Cancer Insitute, National Institutes of Health, Bethesda, Maryland 20892, USA; 2National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA; 3Weill Cornell Medicine, New York, New York 10065, USA; 4Laboratory of Myeloid Malignancies, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA; 5Computational Biology Program, Public Health Sciences and Biological Sciences, Fred Hutchinson Cancer Center, Seattle, Washington 98109, USA Somatic mutations in the genes encoding components of the spliceosome occur frequently in human neoplasms, including myeloid dysplasias and leukemias, and less often in solid tumors. One of the affected factors, U2AF1, is involved in splice site selection, and the most common change, S34F, alters a conserved nucleic acid-binding domain, recognition of the 3′ splice site, and alternative splicing of many mRNAs. However, the role that this mutation plays in oncogenesis is still unknown. Here, we uncovered a noncanonical function of U2AF1, showing that it directly binds mature mRNA in the cytoplasm and negatively regulates mRNA translation. This splicing- independent role of U2AF1 is altered by the S34F mutation, and polysome profiling indicates that the mutation affects translation of hundreds of mRNA. -
Hedgehog Signaling Is Evolutionarily Conserved Cilium-Independent
Downloaded from genesdev.cshlp.org on August 14, 2009 - Published by Cold Spring Harbor Laboratory Press Cilium-independent regulation of Gli protein function by Sufu in Hedgehog signaling is evolutionarily conserved Miao-Hsueh Chen, Christopher W. Wilson, Ya-Jun Li, et al. Genes Dev. 2009 23: 1910-1928 Access the most recent version at doi:10.1101/gad.1794109 Supplemental http://genesdev.cshlp.org/content/suppl/2009/07/23/23.16.1910.DC1.html Material References This article cites 97 articles, 47 of which can be accessed free at: http://genesdev.cshlp.org/content/23/16/1910.full.html#ref-list-1 Email alerting Receive free email alerts when new articles cite this article - sign up in the box at the service top right corner of the article or click here To subscribe to Genes & Development go to: http://genesdev.cshlp.org/subscriptions Copyright © 2009 by Cold Spring Harbor Laboratory Press Downloaded from genesdev.cshlp.org on August 14, 2009 - Published by Cold Spring Harbor Laboratory Press Cilium-independent regulation of Gli protein function by Sufu in Hedgehog signaling is evolutionarily conserved Miao-Hsueh Chen,1,3 Christopher W. Wilson,1,3 Ya-Jun Li,1 Kelvin King Lo Law,2 Chi-Sheng Lu,1 Rhodora Gacayan,1 Xiaoyun Zhang,2 Chi-chung Hui,2 and Pao-Tien Chuang1,4 1Cardiovascular Research Institute, University of California at San Francisco, San Francisco, California 94158, USA; 2Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, and Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5G 1L7, Canada A central question in Hedgehog (Hh) signaling is how evolutionarily conserved components of the pathway might use the primary cilium in mammals but not fly. -
Genetic Mutations Underlying Phenotypic Plasticity in Basosquamous Carcinoma Audris Chiang1,2,7, Caroline Z
See related commentary on pg 2258 ORIGINAL ARTICLE Genetic Mutations Underlying Phenotypic Plasticity in Basosquamous Carcinoma Audris Chiang1,2,7, Caroline Z. Tan1,7, Franc¸ois Kuonen1, Luqman M. Hodgkinson1, Felicia Chiang3, Raymond J. Cho4, Andrew P. South5,JeanY.Tang1, Anne Lynn S. Chang1, Kerri E. Rieger1,6, Anthony E. Oro1 and Kavita Y. Sarin1 Basosquamous carcinoma (BSC) is an aggressive skin neoplasm with the features of both basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). While genetic drivers of BCC and SCC development have been extensively characterized, BSC has not been well studied, and it remains unclear whether these tumors orig- inally derive from BCC or SCC. In addition, it is unknown which molecular pathways mediate the reprog- ramming of tumor keratinocytes toward basaloid or squamatized phenotypes. We sought to characterize the genomic alterations underlying sporadic BSC to elucidate the derivation of these mixed tumors. We identifed frequent Hedgehog (Hh) pathway mutations in BSCs, implicating Hh deregulation as the primary driving event in BSC. Principal component analysis of BCC and SCC driver genes further demonstrate the genetic similarity between BCC and BSC. In addition, 45% of the BSCs harbor recurrent mutations in the SWI/SNF complex gene, ARID1A, and evolutionary analysis revealed that ARID1A mutations occur after PTCH1 but before SCC driver mutations, indicating that ARID1A mutations may bestow plasticity enabling squamatization. Finally, we demonstrate mitogen-activated protein kinase pathway activation and the loss of Hh signaling associated with the squamatization of BSCs. Overall, these results support the genetic derivation of BSCs from BCCs and highlight potential factors involved in modulating tumor reprogramming between basaloid and squamatized phenotypes. -
Sonic Hedgehog-Gli1 Signaling and Cellular Retinoic Acid Binding Protein 1 Gene Regulation in Motor Neuron Differentiation and Diseases
International Journal of Molecular Sciences Article Sonic Hedgehog-Gli1 Signaling and Cellular Retinoic Acid Binding Protein 1 Gene Regulation in Motor Neuron Differentiation and Diseases Yu-Lung Lin y, Yi-Wei Lin y, Jennifer Nhieu y, Xiaoyin Zhang and Li-Na Wei * Department of Pharmacology, University of Minnesota, Minneapolis, MN 55455, USA; [email protected] (Y.-L.L.); [email protected] (Y.-W.L.); [email protected] (J.N.); [email protected] (X.Z.) * Correspondence: [email protected]; Tel.: +1-612-6259402 Contributed equally. y Received: 29 April 2020; Accepted: 7 June 2020; Published: 9 June 2020 Abstract: Cellular retinoic acid-binding protein 1 (CRABP1) is highly expressed in motor neurons. Degenerated motor neuron-like MN1 cells are engineered by introducing SODG93A or AR-65Q to model degenerated amyotrophic lateral sclerosis (ALS) or spinal bulbar muscular atrophy neurons. Retinoic acid (RA)/sonic hedgehog (Shh)-induced embryonic stem cells differentiation into motor neurons are employed to study up-regulation of Crabp1 by Shh. In SODG93A or AR-65Q MN1 neurons, CRABP1 level is reduced, revealing a correlation of motor neuron degeneration with Crabp1 down-regulation. Up-regulation of Crabp1 by Shh is mediated by glioma-associated oncogene homolog 1 (Gli1) that binds the Gli target sequence in Crabp10s neuron-specific regulatory region upstream of minimal promoter. Gli1 binding triggers chromatin juxtaposition with minimal promoter, activating transcription. Motor neuron differentiation and Crabp1 up-regulation are both inhibited by blunting Shh with Gli inhibitor GANT61. Expression data mining of ALS and spinal muscular atrophy (SMA) motor neurons shows reduced CRABP1, coincided with reduction in Shh-Gli1 signaling components. -
Role of Gas1 Down-Regulation in Mitogenic Stimulation of Quiescent NIH3T3 Cells by V-Src
Oncogene (1998) 17, 1629 ± 1638 1998 Stockton Press All rights reserved 0950 ± 9232/98 $12.00 http://www.stockton-press.co.uk/onc Role of Gas1 down-regulation in mitogenic stimulation of quiescent NIH3T3 cells by v-Src Milena Grossi1, S Anna La Rocca1, Gloria Pierluigi1, Serena Vannucchi1, Elisabetta M Ruaro2, Claudio Schneider2 and Franco TatoÁ 1 1Istituto Pasteur-Fondazione Cenci-Bolognetti, Dipartimento di Biologia Cellulare e dello Sviluppo, UniversitaÁ di Roma `La Sapienza', Vie degli Apuli, 100185-Roma, Italy and 2Laboratorio Nazionale Consorzio Interuniversitario per le Biotecnologie, 34012-Trieste, Italy Quiescent mammalian ®broblasts can be induced to re- interfering with the early serum response (Del Sal et enter the cell cycle by growth factors and oncoproteins. al., 1992). Gas1-induced growth arrest appears to be We studied the pathway(s) through which v-Src, the mediated by p53, with no requirement for its sequence- oncogenic tyrosine kinase encoded by the v-src oncogene speci®c transactivating function (Del Sal et al., 1995). of Rous sarcoma virus, forces serum-starved NIH3T3 Ample evidence documents that positive signalling cells to enter S-phase. To this purpose, we isolated and from growth factors and oncogene products very often characterized a polyclonal population of NIH3T3 cells involves the activation of a major biochemical pathway transformed by the MR31 retroviral vector, encoding known as the Ras-pathway (Kazlauskas, 1994; Mar- G418 resistance and the v-src temperature-sensitive allele shall, 1994; McCormick, 1994; Schlessinger, 1994). In from the mutant ts LA31 PR-A. NIH(MR31) cells order to activate this pathway, ultimately leading to S- displayed a temperature-conditional transformed pheno- phase entry, transduction of signals generated at the type and could be made quiescent by serum deprivation cell membrane is needed and performed by adaptor at the restrictive temperature. -
Wt1) – an Effector in Leukemogenesis?
WILMS’ TUMOUR GENE 1 PROTEIN (WT1) – AN EFFECTOR IN LEUKEMOGENESIS? Vidovic, Karina 2010 Link to publication Citation for published version (APA): Vidovic, K. (2010). WILMS’ TUMOUR GENE 1 PROTEIN (WT1) – AN EFFECTOR IN LEUKEMOGENESIS?. Lund University: Faculty of Medicine. Total number of authors: 1 General rights Unless other specific re-use rights are stated the following general rights apply: Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal Read more about Creative commons licenses: https://creativecommons.org/licenses/ Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. LUND UNIVERSITY PO Box 117 221 00 Lund +46 46-222 00 00 Download date: 07. Oct. 2021 Division of Hematology and Transfusion Medicine Lund University, Lund, Sweden WILMS’ TUMOUR GENE 1 PROTEIN (WT1) – AN EFFECTOR IN LEUKEMOGENESIS? Karina Vidovic Thesis 2010 Contact adress Karina Vidovic Division of Hematology and Transfusion Medicine BMC, C14 Klinikgatan 28 SE- 221 84 Lund Sweden Phone +46 46 222 07 30 e-mail: [email protected] ISBN 978-91-86443-99-3 ! Karina Vidovic Printed by Media-Tryck, Lund, Sweden 2 ”The journey of a thousand miles begins with one step” Lao Tzu (Chinese taoist), 600-531 BC 3 4 LIST OF PAPERS This thesis is based on the following papers, referred to in the text by their Roman numerals I. -
An Integrated Genome Screen Identifies the Wnt Signaling Pathway As a Major Target of WT1
An integrated genome screen identifies the Wnt signaling pathway as a major target of WT1 Marianne K.-H. Kima,b, Thomas J. McGarryc, Pilib O´ Broind, Jared M. Flatowb, Aaron A.-J. Goldend, and Jonathan D. Lichta,b,1 aDivision of Hematology/Oncology and cFeinberg Cardiovascular Research Institute, Division of Cardiology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611; bRobert H. Lurie Cancer Center, Northwestern University, Chicago, IL 60611; and dDepartment of Information Technology, National University of Ireland, Galway, Republic of Ireland Edited by Peter K. Vogt, The Scripps Research Institute, La Jolla, CA, and approved May 18, 2009 (received for review February 12, 2009) WT1, a critical regulator of kidney development, is a tumor suppressor control. A first generation of in vitro cotransfection and DNA for nephroblastoma but in some contexts functions as an oncogene. binding assays have given way to more biologically relevant exper- A limited number of direct transcriptional targets of WT1 have been iments where manipulation of WT1 levels has been accompanied identified to explain its complex roles in tumorigenesis and organo- by examination of candidate or global gene expression. Classes of genesis. In this study we performed genome-wide screening for direct WT1 targets thus identified consist of inducers of differentiation, WT1 targets, using a combination of ChIP–ChIP and expression arrays. regulators of cell growth and modulators of cell death. WT1 target Promoter regions bound by WT1 were highly G-rich and resembled genes include CDKN1A (22), a negative regulator of the cell cycle; the sites for a number of other widely expressed transcription factors AREG (23), a facilitator of kidney differentiation; WNT4 (24), a such as SP1, MAZ, and ZNF219. -
Gastrointestinal Defects of the Gas1 Mutant Involve Dysregulated Hedgehog and Ret Signaling
144 Research Article Gastrointestinal defects of the Gas1 mutant involve dysregulated Hedgehog and Ret signaling Sandrine Biau1,2,*, Shiying Jin1,* and Chen-Ming Fan1,` 1Department of Embryology, Carnegie Institution of Washington, 3520 San Martin Drive, Baltimore, Maryland 21218, USA 22iE Foundation, International Institute for Water and Environmental Engineering, Rue de la Science, 01 BP 594, Ouagadougou 01, Burkina Faso *These authors contributed equally to this work `Author for correspondence ([email protected]) Biology Open 2, 144–155 doi: 10.1242/bio.20123186 Received 24th September 2012 Accepted 2nd October 2012 Summary The gastrointestinal (GI) tract defines the digestive system and in the GI tract. Because Gas1 has been shown to inhibit Ret is composed of the stomach, intestine and colon. Among the signaling elicited by Glial cell line-derived neurotrophic factor major cell types lining radially along the GI tract are the (Gdnf), we explored whether Gas1 mutant enteric neurons epithelium, mucosa, smooth muscles and enteric neurons. displayed any alteration of Ret signaling levels. Indeed, isolated The Hedgehog (Hh) pathway has been implicated in directing mutant enteric progenitors not only showed increased levels of various aspects of the developing GI tract, notably the mucosa phospho-Ret and its downstream effectors, phospho-Akt and and smooth muscle growth, and enteric neuron patterning, phospho-Erk, but also displayed altered responses to Gdnf and while the Ret signaling pathway is selectively required for Shh. We therefore conclude that phenotypes observed in the enteric neuron migration, proliferation, and differentiation. The Gas1 mutant are due to a combination of reduced Hh signaling growth arrest specific gene 1 (Gas1) encodes a GPI-anchored and increased Ret signaling. -
Transcriptional Regulation by Extracellular Signals 209
Cell, Vol. 80, 199-211, January 27, 1995, Copyright © 1995 by Cell Press Transcriptional Regulation Review by Extracellular Signals: Mechanisms and Specificity Caroline S. Hill and Richard Treisman Nuclear Translocation Transcription Laboratory In principle, regulated nuclear localization of transcription Imperial Cancer Research Fund factors can involve regulated activity of either nuclear lo- Lincoln's Inn Fields calization signals (NLSs) or cytoplasmic retention signals, London WC2A 3PX although no well-characterized case of the latter has yet England been reported. N LS activity, which is generally dependent on short regions of basic amino acids, can be regulated either by masking mechanisms or by phosphorylations Changes in cell behavior induced by extracellular signal- within the NLS itself (Hunter and Karin, 1992). For exam- ing molecules such as growth factors and cytokines re- ple, association with an inhibitory subunit masks the NLS quire execution of a complex program of transcriptional of NF-KB and its relatives (Figure 1; for review see Beg events. While the route followed by the intracellular signal and Baldwin, 1993), while an intramolecular mechanism from the cell membrane to its transcription factor targets may mask NLS activity in the heat shock regulatory factor can be traced in an increasing number of cases, how the HSF2 (Sheldon and Kingston, 1993). When transcription specificity of the transcriptional response of the cell to factor localization is dependent on regulated NLS activity, different stimuli is determined is much less clear. How- linkage to a constitutively acting NLS may be sufficient to ever, it is possible to understand at least in principle how render nuclear localization independent of signaling (Beg different stimuli can activate the same signal pathway yet et al., 1992). -
Homeobox Gene Expression Profile in Human Hematopoietic Multipotent
Leukemia (2003) 17, 1157–1163 & 2003 Nature Publishing Group All rights reserved 0887-6924/03 $25.00 www.nature.com/leu Homeobox gene expression profile in human hematopoietic multipotent stem cells and T-cell progenitors: implications for human T-cell development T Taghon1, K Thys1, M De Smedt1, F Weerkamp2, FJT Staal2, J Plum1 and G Leclercq1 1Department of Clinical Chemistry, Microbiology and Immunology, Ghent University Hospital, Ghent, Belgium; and 2Department of Immunology, Erasmus Medical Center, Rotterdam, The Netherlands Class I homeobox (HOX) genes comprise a large family of implicated in this transformation proces.14 The HOX-C locus transcription factors that have been implicated in normal and has been primarily implicated in lymphomas.15 malignant hematopoiesis. However, data on their expression or function during T-cell development is limited. Using degener- Hematopoietic cells are derived from stem cells that reside in ated RT-PCR and Affymetrix microarray analysis, we analyzed fetal liver (FL) in the embryo and in the adult bone marrow the expression pattern of this gene family in human multipotent (ABM), which have the unique ability to self-renew and thereby stem cells from fetal liver (FL) and adult bone marrow (ABM), provide a life-long supply of blood cells. T lymphocytes are a and in T-cell progenitors from child thymus. We show that FL specific type of hematopoietic cells that play a major role in the and ABM stem cells are similar in terms of HOX gene immune system. They develop through a well-defined order of expression, but significant differences were observed between differentiation steps in the thymus.16 Several transcription these two cell types and child thymocytes. -
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. -
Supplemental Materials ZNF281 Enhances Cardiac Reprogramming
Supplemental Materials ZNF281 enhances cardiac reprogramming by modulating cardiac and inflammatory gene expression Huanyu Zhou, Maria Gabriela Morales, Hisayuki Hashimoto, Matthew E. Dickson, Kunhua Song, Wenduo Ye, Min S. Kim, Hanspeter Niederstrasser, Zhaoning Wang, Beibei Chen, Bruce A. Posner, Rhonda Bassel-Duby and Eric N. Olson Supplemental Table 1; related to Figure 1. Supplemental Table 2; related to Figure 1. Supplemental Table 3; related to the “quantitative mRNA measurement” in Materials and Methods section. Supplemental Table 4; related to the “ChIP-seq, gene ontology and pathway analysis” and “RNA-seq” and gene ontology analysis” in Materials and Methods section. Supplemental Figure S1; related to Figure 1. Supplemental Figure S2; related to Figure 2. Supplemental Figure S3; related to Figure 3. Supplemental Figure S4; related to Figure 4. Supplemental Figure S5; related to Figure 6. Supplemental Table S1. Genes included in human retroviral ORF cDNA library. Gene Gene Gene Gene Gene Gene Gene Gene Symbol Symbol Symbol Symbol Symbol Symbol Symbol Symbol AATF BMP8A CEBPE CTNNB1 ESR2 GDF3 HOXA5 IL17D ADIPOQ BRPF1 CEBPG CUX1 ESRRA GDF6 HOXA6 IL17F ADNP BRPF3 CERS1 CX3CL1 ETS1 GIN1 HOXA7 IL18 AEBP1 BUD31 CERS2 CXCL10 ETS2 GLIS3 HOXB1 IL19 AFF4 C17ORF77 CERS4 CXCL11 ETV3 GMEB1 HOXB13 IL1A AHR C1QTNF4 CFL2 CXCL12 ETV7 GPBP1 HOXB5 IL1B AIMP1 C21ORF66 CHIA CXCL13 FAM3B GPER HOXB6 IL1F3 ALS2CR8 CBFA2T2 CIR1 CXCL14 FAM3D GPI HOXB7 IL1F5 ALX1 CBFA2T3 CITED1 CXCL16 FASLG GREM1 HOXB9 IL1F6 ARGFX CBFB CITED2 CXCL3 FBLN1 GREM2 HOXC4 IL1F7