Lamin B1 Is Required for Mature Neuron-Specific Gene Expression
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The Role of Nuclear Lamin B1 in Cell Proliferation and Senescence
Downloaded from genesdev.cshlp.org on September 29, 2021 - Published by Cold Spring Harbor Laboratory Press The role of nuclear lamin B1 in cell proliferation and senescence Takeshi Shimi,1 Veronika Butin-Israeli,1 Stephen A. Adam,1 Robert B. Hamanaka,2 Anne E. Goldman,1 Catherine A. Lucas,1 Dale K. Shumaker,1 Steven T. Kosak,1 Navdeep S. Chandel,2 and Robert D. Goldman1,3 1Department of Cell and Molecular Biology, 2Department of Medicine, Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA Nuclear lamin B1 (LB1) is a major structural component of the nucleus that appears to be involved in the regulation of many nuclear functions. The results of this study demonstrate that LB1 expression in WI-38 cells decreases during cellular senescence. Premature senescence induced by oncogenic Ras also decreases LB1 expression through a retinoblastoma protein (pRb)-dependent mechanism. Silencing the expression of LB1 slows cell proliferation and induces premature senescence in WI-38 cells. The effects of LB1 silencing on proliferation require the activation of p53, but not pRb. However, the induction of premature senescence requires both p53 and pRb. The proliferation defects induced by silencing LB1 are accompanied by a p53-dependent reduction in mitochondrial reactive oxygen species (ROS), which can be rescued by growth under hypoxic conditions. In contrast to the effects of LB1 silencing, overexpression of LB1 increases the proliferation rate and delays the onset of senescence of WI-38 cells. This overexpression eventually leads to cell cycle arrest at the G1/S boundary. -
Revealing the Mechanism of Xist-Mediated Silencing
Revealing the Mechanism of Xist-mediated Silencing Thesis by Chun-Kan Chen In Partial Fulfillment of the Requirements for the degree of Doctor of Philosophy CALIFORNIA INSTITUTE OF TECHNOLOGY Pasadena, California 2018 Defended November 1, 2017 ii 2017 Chun-Kan Chen ORCID: 0000-0002-1194-9137 iii ACKNOWLEDGEMENTS First of all, I’d like to thank my great mentor, Dr. Mitch Guttman (California Institute of Technology, Pasadena, CA), who led me to become an independent researcher and gave me valuable advice that guided me to accomplish this thesis. He has always been supportive of my future plans and career goals. I really enjoyed every discussion we have had. We often generated some interesting ideas for projects during our discussions. I would also like to send my thanks to my lab mates, Amy Chow, Mario Blanco, and Erik Aznauryan, who helped me with many experiments to move the project forward. I’d like to acknowledge Dr. Kathrin Plath (University of California, Los Angeles, Los Angeles, CA) for the collaboration and his critical comments on this project. Also, I want to thank Jesse Engreitz and Patrick McDonel, who provided helpful comments and suggestions to the project. I want to thank my parents, brother, and parents-in-law who provided both instrumental and emotional support to assist me in completing my Ph.D. degree. I also want to thank my friends, Lily Chen, Pei-Ying Lin, Tzu-Yao Wang, and Wei Li, for giving me valuable social support during my years in graduate school. Last but not least, I would like to send my special thanks to my wife, Christine Juang, who has always been supportive. -
Myosin Myth4-FERM Structures Highlight Important Principles of Convergent Evolution
Myosin MyTH4-FERM structures highlight important principles of convergent evolution Vicente José Planelles-Herreroa,b, Florian Blanca,c, Serena Sirigua, Helena Sirkiaa, Jeffrey Clausea, Yannick Souriguesa, Daniel O. Johnsrudd, Beatrice Amiguesa, Marco Cecchinic, Susan P. Gilberte, Anne Houdussea,1,2, and Margaret A. Titusd,1,2 aStructural Motility, Institut Curie, CNRS, UMR 144, PSL Research University, F-75005 Paris, France; bUPMC Université de Paris 6, Institut de Formation Doctorale, Sorbonne Universités, 75252 Paris Cedex 05, France; cLaboratoire d’Ingénierie des Fonctions Moléculaires, Institut de Science et d’Ingénierie Supramoléculaires, UMR 7006 CNRS, Université de Strasbourg, F-67083 Strasbourg Cedex, France; dDepartment of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN 55455; and eDepartment of Biological Sciences, Rensselaer Polytechnic Institute, Troy, NY 12180 Edited by James A. Spudich, Stanford University School of Medicine, Stanford, CA, and approved March 31, 2016 (received for review January 15, 2016) Myosins containing MyTH4-FERM (myosin tail homology 4-band (Fig. 1). These MF myosins are widespread and likely quite an- 4.1, ezrin, radixin, moesin, or MF) domains in their tails are found cient because they are found in many different branches of the in a wide range of phylogenetically divergent organisms, such as phylogenetic tree (5, 6), including Opisthokonts (which includes humans and the social amoeba Dictyostelium (Dd). Interestingly, Metazoa, unicellular Holozoa, and Fungi), Amoebozoa, and the evolutionarily distant MF myosins have similar roles in the exten- SAR (Stramenopiles, Alveolates, and Rhizaria) (Fig. 1 A and B). sion of actin-filled membrane protrusions such as filopodia and Over the course of hundreds of millions years of parallel evolution bind to microtubules (MT), suggesting that the core functions of the MF myosins have acquired or maintained roles in the formation these MF myosins have been highly conserved over evolution. -
The Roles of Histone Deacetylase 5 and the Histone Methyltransferase Adaptor WDR5 in Myc Oncogenesis
The Roles of Histone Deacetylase 5 and the Histone Methyltransferase Adaptor WDR5 in Myc oncogenesis By Yuting Sun This thesis is submitted in fulfilment of the requirements for the degree of Doctor of Philosophy at the University of New South Wales Children’s Cancer Institute Australia for Medical Research School of Women’s and Children’s Health, Faculty of Medicine University of New South Wales Australia August 2014 PLEASE TYPE THE UNIVERSITY OF NEW SOUTH WALES Thesis/Dissertation Sheet Surname or Family name: Sun First name: Yuting Other name/s: Abbreviation for degree as given in the University calendar: PhD School : School of·Women's and Children's Health Faculty: Faculty of Medicine Title: The Roles of Histone Deacetylase 5 and the Histone Methyltransferase Adaptor WDR5 in Myc oncogenesis. Abstract 350 words maximum: (PLEASE TYPE) N-Myc Induces neuroblastoma by regulating the expression of target genes and proteins, and N-Myc protein is degraded by Fbxw7 and NEDD4 and stabilized by Aurora A. The class lla histone deacetylase HDAC5 suppresses gene transcription, and blocks myoblast and leukaemia cell differentiation. While histone H3 lysine 4 (H3K4) trimethylation at target gene promoters is a pre-requisite for Myc· induced transcriptional activation, WDRS, as a histone H3K4 methyltransferase presenter, is required for H3K4 methylation and transcriptional activation mediated by a histone H3K4 methyltransferase complex. Here, I investigated the roles of HDAC5 and WDR5 in N-Myc overexpressing neuroblastoma. I have found that N-Myc upregulates HDAC5 protein expression, and that HDAC5 represses NEDD4 gene expression, increases Aurora A gene expression and consequently upregulates N-Myc protein expression in neuroblastoma cells. -
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. -
Nuclear Matrix
Nuclear matrix, nuclear envelope and premature aging syndromes in a translational research perspective Pierre Cau, Claire Navarro, Karim Harhouri, Patrice Roll, Sabine Sigaudy, Elise Kaspi, Sophie Perrin, Annachiara de Sandre-Giovannoli, Nicolas Lévy To cite this version: Pierre Cau, Claire Navarro, Karim Harhouri, Patrice Roll, Sabine Sigaudy, et al.. Nuclear matrix, nuclear envelope and premature aging syndromes in a translational research perspective. Seminars in Cell and Developmental Biology, Elsevier, 2014, 29, pp.125-147. 10.1016/j.semcdb.2014.03.021. hal-01646524 HAL Id: hal-01646524 https://hal-amu.archives-ouvertes.fr/hal-01646524 Submitted on 20 Dec 2017 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Review Nuclear matrix, nuclear envelope and premature aging syndromes in a translational research perspective Pierre Cau a,b,c,∗, Claire Navarro a,b,1, Karim Harhouri a,b,1, Patrice Roll a,b,c,1,2, Sabine Sigaudy a,b,d,1,3, Elise Kaspi a,b,c,1,2, Sophie Perrin a,b,1, Annachiara De Sandre-Giovannoli a,b,d,1,3, Nicolas Lévy a,b,d,∗∗ a Aix-Marseille -
Supplementary Materials
1 Supplementary Materials: Supplemental Figure 1. Gene expression profiles of kidneys in the Fcgr2b-/- and Fcgr2b-/-. Stinggt/gt mice. (A) A heat map of microarray data show the genes that significantly changed up to 2 fold compared between Fcgr2b-/- and Fcgr2b-/-. Stinggt/gt mice (N=4 mice per group; p<0.05). Data show in log2 (sample/wild-type). 2 Supplemental Figure 2. Sting signaling is essential for immuno-phenotypes of the Fcgr2b-/-lupus mice. (A-C) Flow cytometry analysis of splenocytes isolated from wild-type, Fcgr2b-/- and Fcgr2b-/-. Stinggt/gt mice at the age of 6-7 months (N= 13-14 per group). Data shown in the percentage of (A) CD4+ ICOS+ cells, (B) B220+ I-Ab+ cells and (C) CD138+ cells. Data show as mean ± SEM (*p < 0.05, **p<0.01 and ***p<0.001). 3 Supplemental Figure 3. Phenotypes of Sting activated dendritic cells. (A) Representative of western blot analysis from immunoprecipitation with Sting of Fcgr2b-/- mice (N= 4). The band was shown in STING protein of activated BMDC with DMXAA at 0, 3 and 6 hr. and phosphorylation of STING at Ser357. (B) Mass spectra of phosphorylation of STING at Ser357 of activated BMDC from Fcgr2b-/- mice after stimulated with DMXAA for 3 hour and followed by immunoprecipitation with STING. (C) Sting-activated BMDC were co-cultured with LYN inhibitor PP2 and analyzed by flow cytometry, which showed the mean fluorescence intensity (MFI) of IAb expressing DC (N = 3 mice per group). 4 Supplemental Table 1. Lists of up and down of regulated proteins Accession No. -
(RRP1B) Modulates Metastasis Through Regulation of Histone Methylation
Published OnlineFirst August 4, 2014; DOI: 10.1158/1541-7786.MCR-14-0167 Molecular Cancer Oncogenes and Tumor Suppressors Research Metastasis-Associated Protein Ribosomal RNA Processing 1 Homolog B (RRP1B) Modulates Metastasis through Regulation of Histone Methylation Minnkyong Lee1, Amy M. Dworkin1, Jens Lichtenberg1, Shashank J. Patel1, Niraj S. Trivedi2, Derek Gildea2, David M. Bodine1, and Nigel P.S. Crawford1 Abstract Overexpression of ribosomal RNA processing 1 homolog B (RRP1B) induces a transcriptional profile that accurately predicts patient outcome in breast cancer. However, the mechanism by which RRP1B modulates transcription is unclear. Here, the chromatin-binding properties of RRP1B were examined to define how it regulates metastasis-associated transcription. To identify genome-wide RRP1B-binding sites, high-throughput ChIP-seq was performed in the human breast cancer cell line MDA-MB-231 and HeLa cells using antibodies against endogenous RRP1B. Global changes in repressive marks such as histone H3 lysine 9 trimethylation (H3K9me3) were also examined by ChIP-seq. Analysis of these samples identified 339 binding regions in MDA- MB-231 cells and 689 RRP1B-binding regions in HeLa cells. Among these, 136 regions were common to both cell lines. Gene expression analyses of these RRP1B-binding regions revealed that transcriptional repression is the primary result of RRP1B binding to chromatin. ChIP-reChIP assays demonstrated that RRP1B co-occupies loci with decreased gene expression with the heterochromatin-associated proteins, tripartite motif-containing protein 28 (TRIM28/KAP1), and heterochromatin protein 1-a (CBX5/HP1a). RRP1B occupancy at these loci was also associated with higher H3K9me3 levels, indicative of heterochromatinization mediated by the TRIM28/HP1a complex. -
Spectrum of MYO7A Mutations in an Indigenous South African
G C A T T A C G G C A T genes Article Spectrum of MYO7A Mutations in an Indigenous South African Population Further Elucidates the Nonsyndromic Autosomal Recessive Phenotype of DFNB2 to Include Both Homozygous and Compound Heterozygous Mutations Rosemary Ida Kabahuma 1,2,*, Wolf-Dieter Schubert 2, Christiaan Labuschagne 3, Denise Yan 4, Susan Halloran Blanton 4,5 , Michael Sean Pepper 6 and Xue Zhong Liu 4,5,* 1 Department of Otorhinolaryngology, University of Pretoria, Pretoria 0001, South Africa 2 Departments of Biochemistry, Genetics and Microbiology, Faculty of Natural and Agricultural Sciences, University of Pretoria, Pretoria 0001, South Africa; [email protected] 3 Inqaba Biotechnical Industries, Pretoria 0002, South Africa; [email protected] 4 Department Otolaryngology, University of Miami Miller School of Medicine, Miami, FL 33136, USA; [email protected] (D.Y.); [email protected] (S.H.B.) 5 Dr. John T. Macdonald Foundation Department of Human Genetics, and John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL 33136, USA 6 Department Immunology and SAMRC Extramural Unit for Stem Cell Research and Therapy, Faculty of Health Sciences, Institute for Cellular and Molecular Medicine, University of Pretoria, Citation: Kabahuma, R.I.; Pretoria 0001, South Africa; [email protected] Schubert, W.-D.; Labuschagne, C.; * Correspondence: [email protected] (R.I.K.); [email protected] (X.Z.L.) Yan, D.; Blanton, S.H.; Pepper, M.S.; Liu, X.Z. Spectrum of MYO7A Abstract: MYO7A gene encodes unconventional myosin VIIA, which, when mutated, causes a phe- Mutations in an Indigenous South notypic spectrum ranging from recessive hearing loss DFNB2 to deaf-blindness, Usher Type 1B African Population Further (USH1B). -
Non-Coding RNA: X-Chromosome Inactivation Unravelled
RESEARCH HIGHLIGHTS Nature Reviews Molecular Cell Biology | AOP, published online 8 May 2015; doi:10.1038/nrm3998 NON-CODING RNA X-chromosome inactivation unravelled The long non-coding RNA (lncRNA) specific and reproducible set of ten suggesting that SAFA acts to localize Xist (X inactive-specific transcript) is proteins that directly interact with Xist to genomic DNA. Depleting required for the transcriptional silenc- Xist. Of these proteins, knocking Xist binds to SHARP led to the retention of Pol II ing of one X chromosome in each cell, down the genes encoding scaffold SHARP to at Xist-coated X chromosomes, in a process known as X-chromosome attachment factor A (SAFA; also recruit SMRT indicating that SHARP might be inactivation (XCI) that occurs during known as HNRNPU), SMRT- and required for initiating transcriptional mammalian female development. HDAC1-associated repressor protein and activate silencing following Xist localization, Owing to technical limitations, little (SHARP; also known as SPEN or HDAC3 … possibly by recruiting the transcrip- is known about the mechanism of MSX2-interacting protein) and resulting in tional co-repressors SMRT and transcriptional silencing during XCI. lamin-B receptor (LBR) largely abol- HDAC3. Indeed, depleting SMRT McHugh et al. now describe using ished the silencing of XCI‑affected gene silencing or HDAC3 (but not other HDACs) RNA antisense purification followed genes in the male ES cells as well as in abrogated Xist-dependent gene by quantitative mass spectrometry differentiating female ES cells. These silencing. Another feature of XCI (RAP–MS) — a novel approach for three proteins are therefore required is the recruitment of the Polycomb identifying proteins that directly for Xist-mediated gene silencing. -
Ion Channels 3 1
r r r Cell Signalling Biology Michael J. Berridge Module 3 Ion Channels 3 1 Module 3 Ion Channels Synopsis Ion channels have two main signalling functions: either they can generate second messengers or they can function as effectors by responding to such messengers. Their role in signal generation is mainly centred on the Ca2 + signalling pathway, which has a large number of Ca2+ entry channels and internal Ca2+ release channels, both of which contribute to the generation of Ca2 + signals. Ion channels are also important effectors in that they mediate the action of different intracellular signalling pathways. There are a large number of K+ channels and many of these function in different + aspects of cell signalling. The voltage-dependent K (KV) channels regulate membrane potential and + excitability. The inward rectifier K (Kir) channel family has a number of important groups of channels + + such as the G protein-gated inward rectifier K (GIRK) channels and the ATP-sensitive K (KATP) + + channels. The two-pore domain K (K2P) channels are responsible for the large background K current. Some of the actions of Ca2 + are carried out by Ca2+-sensitive K+ channels and Ca2+-sensitive Cl − channels. The latter are members of a large group of chloride channels and transporters with multiple functions. There is a large family of ATP-binding cassette (ABC) transporters some of which have a signalling role in that they extrude signalling components from the cell. One of the ABC transporters is the cystic − − fibrosis transmembrane conductance regulator (CFTR) that conducts anions (Cl and HCO3 )and contributes to the osmotic gradient for the parallel flow of water in various transporting epithelia. -
Lamin B2 Follows Lamin A/C- Mediated Nuclear Mechanics and Cancer Cell Invasion Efficacy
bioRxiv preprint doi: https://doi.org/10.1101/2020.04.07.028969; this version posted April 8, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Lamin B2 follows lamin A/C- mediated nuclear mechanics and cancer cell invasion efficacy Short running title: Nuclear lamins in tumor cell migration Marina Vortmeyer-Krause1†, Mariska te Lindert1†, Joost te Riet2†, Veronika te Boekhorst1†, Rene Marke1, Ramanil Perera1, Philipp Isermann3, Tom van Oorschot1, Monika Zwerger3, Fengwei Yang4, Martin Svoreň1, Anotida Madzvamuse 4, Jan Lammerding3, Peter Friedl1,5,6, Katarina Wolf1* †These authors contributed equally to this work. * Correspondence to: [email protected] *Address of corresponding author: Department of Cell Biology (route 283), Radboud University Medical Center, PO Box 9101, 6500 HB Nijmegen, The Netherlands; [email protected]; Orcid: http://orcid.org/0000-0003-0616-2708 Affiliations 1 Radboud University Medical Center, Department of Cell Biology, 6500 HB Nijmegen, The Netherlands 2 Radboud University Medical Center, Department of Tumor Immunology, 6500 HB Nijmegen, The Netherlands 3 Weill Institute for Cell and Molecular Biology, Meinig School of Biomedical Engineering Cornell University, Ithaca, NY 14853; USA 4 School of Mathematical and Physical Sciences, University of Sussex, Department of Mathematics, BN1 9QH, Falmer, Brighton, United Kingdom 5 David H. Koch Center for Applied Research of Genitourinary Cancers, Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA 6 Cancer Genomics Center, 3584 CG Utrecht, The Netherlands 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.04.07.028969; this version posted April 8, 2020.