Twisting an Embryonic Transcription Factor Into an Oncoprotein
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Uterine Double-Conditional Inactivation of Smad2 and Smad3 in Mice Causes Endometrial Dysregulation, Infertility, and Uterine Cancer
Uterine double-conditional inactivation of Smad2 and Smad3 in mice causes endometrial dysregulation, infertility, and uterine cancer Maya Krisemana,b, Diana Monsivaisa,c, Julio Agnoa, Ramya P. Masanda, Chad J. Creightond,e, and Martin M. Matzuka,c,f,g,h,1 aDepartment of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030; bReproductive Endocrinology and Infertility, Baylor College of Medicine/Texas Children’s Hospital Women’s Pavilion, Houston, TX 77030; cCenter for Drug Discovery, Baylor College of Medicine, Houston, TX 77030; dDepartment of Medicine, Baylor College of Medicine, Houston, TX 77030; eDan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030; fDepartment of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030; gDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030; and hDepartment of Pharmacology and Chemical Biology, Baylor College of Medicine, Houston, TX 77030 Contributed by Martin M. Matzuk, December 6, 2018 (sent for review April 30, 2018; reviewed by Milan K. Bagchi and Thomas E. Spencer) SMAD2 and SMAD3 are downstream proteins in the transforming in endometrial function. Notably, members of the transforming growth factor-β (TGF β) signaling pathway that translocate signals growth factor β (TGF β) family are involved in many cellular from the cell membrane to the nucleus, bind DNA, and control the processes and serve as principal regulators of numerous biological expression of target genes. While SMAD2/3 have important roles functions, including female reproduction. Previous studies have in the ovary, we do not fully understand the roles of SMAD2/3 in shown the TGF β family to have key roles in ovarian folliculo- the uterus and their implications in the reproductive system. -
Supplemental Figures
A B Previously-induced Doxycycline-naïve survival (%) survival (%) Recurrence-free Recurrence-free Days following dox withdrawal Age C D Primary Recurrent ** Par-4 mRNA H2B-mCherry DAPI Primary Recurrent Supplemental Figure 1: Recurrent tumors are derived from primary tumors. A. Kaplan-Meier survival plot showing recurrent tumor-free survival in mice previously induced with doxycycline (n=30) or tumor-free survival in doxycycline-naïve mice (n=10). B. Kaplan-Meier survival plot showing recurrence-free survival following doxycycline withdrawal in a cohort of recipient mice with orthotopic tumors (n=5). C. Representative images (40x magnification) of primary and recurrent orthotopic tumors following injection of H2B-mCherry labeled primary tumor cell line #1 into recipient mice. D. qRT-PCR analysis of Par-4 transcripts from primary (n=5) and recurrent (n=5) orthotopic tumors. Significance determined by Student’s t-test. Error bars denote mean ± SEM. **p<0.01. A B 1 TWIST1 TWIST2 0.5 SNAI2 0 VIM -0.5 ZEB1 ZEB2 -1 SNAI1 PAWR Positively correlated Negatively correlated with Par-4 with Par-4 CDH1 CLDN7 CLDN4 CLDN3 KRT18 NES = -2.07335 q-value = 0.001129 KRT8 TWIST1 TWIST2 SNAI2 VIM ZEB1 ZEB2 SNAI1 PAWR CDH1 CLDN7 CLDN4 CLDN3 KRT18 KRT8 Marcotte, et al. C 1 SNAI1 0.5 TWIST1 TWIST2 0 VIM -0.5 SNAI2 -1 ZEB1 ZEB2 PAWR CDH1 KRT18 KRT8 CLDN7 CLDN3 CLDN4 SNAI1 TWIST1 TWIST2 VIM SNAI2 ZEB1 ZEB2 PAWR CDH1 KRT18 KRT8 CLDN7 CLDN3 CLDN4 TCGA, Cell 2015 Supplemental Figure 2: Par-4 expression is negatively correlated with EMT in human breast cancer. A. -
Functional Roles of Bromodomain Proteins in Cancer
cancers Review Functional Roles of Bromodomain Proteins in Cancer Samuel P. Boyson 1,2, Cong Gao 3, Kathleen Quinn 2,3, Joseph Boyd 3, Hana Paculova 3 , Seth Frietze 3,4,* and Karen C. Glass 1,2,4,* 1 Department of Pharmaceutical Sciences, Albany College of Pharmacy and Health Sciences, Colchester, VT 05446, USA; [email protected] 2 Department of Pharmacology, Larner College of Medicine, University of Vermont, Burlington, VT 05405, USA; [email protected] 3 Department of Biomedical and Health Sciences, University of Vermont, Burlington, VT 05405, USA; [email protected] (C.G.); [email protected] (J.B.); [email protected] (H.P.) 4 University of Vermont Cancer Center, Burlington, VT 05405, USA * Correspondence: [email protected] (S.F.); [email protected] (K.C.G.) Simple Summary: This review provides an in depth analysis of the role of bromodomain-containing proteins in cancer development. As readers of acetylated lysine on nucleosomal histones, bromod- omain proteins are poised to activate gene expression, and often promote cancer progression. We examined changes in gene expression patterns that are observed in bromodomain-containing proteins and associated with specific cancer types. We also mapped the protein–protein interaction network for the human bromodomain-containing proteins, discuss the cellular roles of these epigenetic regu- lators as part of nine different functional groups, and identify bromodomain-specific mechanisms in cancer development. Lastly, we summarize emerging strategies to target bromodomain proteins in cancer therapy, including those that may be essential for overcoming resistance. Overall, this review provides a timely discussion of the different mechanisms of bromodomain-containing pro- Citation: Boyson, S.P.; Gao, C.; teins in cancer, and an updated assessment of their utility as a therapeutic target for a variety of Quinn, K.; Boyd, J.; Paculova, H.; cancer subtypes. -
Segmentation in Vertebrates: Clock and Gradient Finally Joined
Downloaded from genesdev.cshlp.org on September 24, 2021 - Published by Cold Spring Harbor Laboratory Press REVIEW Segmentation in vertebrates: clock and gradient finally joined Alexander Aulehla1 and Bernhard G. Herrmann2 Max-Planck-Institute for Molecular Genetics, Department of Developmental Genetics, 14195 Berlin, Germany The vertebral column is derived from somites formed by terior (A–P) axis. Somite formation takes place periodi- segmentation of presomitic mesoderm, a fundamental cally in a fixed anterior-to-posterior sequence. process of vertebrate embryogenesis. Models on the In the chick embryo, a new somite is formed approxi- mechanism controlling this process date back some mately every 90 min, whereas in the mouse embryo, the three to four decades. Access to understanding the mo- periodicity varies, dependent on the axial position (Tam lecular control of somitogenesis has been gained only 1981). Classical embryology experiments revealed that recently by the discovery of molecular oscillators (seg- periodicity and directionality of somite formation are mentation clock) and gradients of signaling molecules, controlled by an intrinsic program set off in the cells as as predicted by early models. The Notch signaling path- they are recruited into the psm. For instance, when the way is linked to the oscillator and plays a decisive role in psm is inverted rostro–caudally, somite formation in the inter- and intrasomitic boundary formation. An Fgf8 sig- inverted region proceeds from caudal to rostral, main- naling gradient is involved in somite size control. And taining the original direction (Christ et al. 1974). More- the (canonical) Wnt signaling pathway, driven by Wnt3a, over, neither the transversal bisection nor the isolation appears to integrate clock and gradient in a global of the psm from all surrounding tissues stops the seg- mechanism controlling the segmentation process. -
Dermo-1: a Novel Twist-Related Bhlh Protein Expressed in The
DEVELOPMENTAL BIOLOGY 172, 280±292 (1995) Dermo-1: A Novel Twist-Related bHLH Protein View metadata,Expressed citation and similar in papers the at core.ac.uk Developing Dermis brought to you by CORE provided by Elsevier - Publisher Connector Li Li, Peter Cserjesi,1 and Eric N. Olson2 Department of Biochemistry and Molecular Biology, Box 117, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030 Transcription factors belonging to the basic helix±loop±helix (bHLH) family have been shown to control differentiation of a variety of cell types. Tissue-speci®c bHLH proteins dimerize preferentially with ubiquitous bHLH proteins to form heterodimers that bind the E-box consensus sequence (CANNTG) in the control regions of target genes. Using the yeast two-hybrid system to screen for tissue-speci®c bHLH proteins, which dimerize with the ubiquitous bHLH protein E12, we cloned a novel bHLH protein, named Dermo-1. Within its bHLH region, Dermo-1 shares extensive homology with members of the twist family of bHLH proteins, which are expressed in embryonic mesoderm. During mouse embryogenesis, Dermo- 1 showed an expression pattern similar to, but distinct from, that of mouse twist. Dermo-1 was expressed at a low level in the sclerotome and dermatome of the somites, and in the limb buds at Day 10.5 post coitum (p.c.), and accumulated predominantly in the dermatome, prevertebrae, and the derivatives of the branchial arches by Day 13.5 p.c. As differentiation of prechondrial cells proceeded, Dermo-1 expression became restricted to the perichondrium. Expression of Dermo-1 increased continuously in the dermis through Day 17.5 p.c. -
The Title of the Dissertation
UNIVERSITY OF CALIFORNIA SAN DIEGO Novel network-based integrated analyses of multi-omics data reveal new insights into CD8+ T cell differentiation and mouse embryogenesis A dissertation submitted in partial satisfaction of the requirements for the degree Doctor of Philosophy in Bioinformatics and Systems Biology by Kai Zhang Committee in charge: Professor Wei Wang, Chair Professor Pavel Arkadjevich Pevzner, Co-Chair Professor Vineet Bafna Professor Cornelis Murre Professor Bing Ren 2018 Copyright Kai Zhang, 2018 All rights reserved. The dissertation of Kai Zhang is approved, and it is accept- able in quality and form for publication on microfilm and electronically: Co-Chair Chair University of California San Diego 2018 iii EPIGRAPH The only true wisdom is in knowing you know nothing. —Socrates iv TABLE OF CONTENTS Signature Page ....................................... iii Epigraph ........................................... iv Table of Contents ...................................... v List of Figures ........................................ viii List of Tables ........................................ ix Acknowledgements ..................................... x Vita ............................................. xi Abstract of the Dissertation ................................. xii Chapter 1 General introduction ............................ 1 1.1 The applications of graph theory in bioinformatics ......... 1 1.2 Leveraging graphs to conduct integrated analyses .......... 4 1.3 References .............................. 6 Chapter 2 Systematic -
Table S1 the Four Gene Sets Derived from Gene Expression Profiles of Escs and Differentiated Cells
Table S1 The four gene sets derived from gene expression profiles of ESCs and differentiated cells Uniform High Uniform Low ES Up ES Down EntrezID GeneSymbol EntrezID GeneSymbol EntrezID GeneSymbol EntrezID GeneSymbol 269261 Rpl12 11354 Abpa 68239 Krt42 15132 Hbb-bh1 67891 Rpl4 11537 Cfd 26380 Esrrb 15126 Hba-x 55949 Eef1b2 11698 Ambn 73703 Dppa2 15111 Hand2 18148 Npm1 11730 Ang3 67374 Jam2 65255 Asb4 67427 Rps20 11731 Ang2 22702 Zfp42 17292 Mesp1 15481 Hspa8 11807 Apoa2 58865 Tdh 19737 Rgs5 100041686 LOC100041686 11814 Apoc3 26388 Ifi202b 225518 Prdm6 11983 Atpif1 11945 Atp4b 11614 Nr0b1 20378 Frzb 19241 Tmsb4x 12007 Azgp1 76815 Calcoco2 12767 Cxcr4 20116 Rps8 12044 Bcl2a1a 219132 D14Ertd668e 103889 Hoxb2 20103 Rps5 12047 Bcl2a1d 381411 Gm1967 17701 Msx1 14694 Gnb2l1 12049 Bcl2l10 20899 Stra8 23796 Aplnr 19941 Rpl26 12096 Bglap1 78625 1700061G19Rik 12627 Cfc1 12070 Ngfrap1 12097 Bglap2 21816 Tgm1 12622 Cer1 19989 Rpl7 12267 C3ar1 67405 Nts 21385 Tbx2 19896 Rpl10a 12279 C9 435337 EG435337 56720 Tdo2 20044 Rps14 12391 Cav3 545913 Zscan4d 16869 Lhx1 19175 Psmb6 12409 Cbr2 244448 Triml1 22253 Unc5c 22627 Ywhae 12477 Ctla4 69134 2200001I15Rik 14174 Fgf3 19951 Rpl32 12523 Cd84 66065 Hsd17b14 16542 Kdr 66152 1110020P15Rik 12524 Cd86 81879 Tcfcp2l1 15122 Hba-a1 66489 Rpl35 12640 Cga 17907 Mylpf 15414 Hoxb6 15519 Hsp90aa1 12642 Ch25h 26424 Nr5a2 210530 Leprel1 66483 Rpl36al 12655 Chi3l3 83560 Tex14 12338 Capn6 27370 Rps26 12796 Camp 17450 Morc1 20671 Sox17 66576 Uqcrh 12869 Cox8b 79455 Pdcl2 20613 Snai1 22154 Tubb5 12959 Cryba4 231821 Centa1 17897 -
Estrogen-Related Receptor Alpha: an Under-Appreciated Potential Target for the Treatment of Metabolic Diseases
International Journal of Molecular Sciences Review Estrogen-Related Receptor Alpha: An Under-Appreciated Potential Target for the Treatment of Metabolic Diseases Madhulika Tripathi, Paul Michael Yen and Brijesh Kumar Singh * Laboratory of Hormonal Regulation, Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School, Singapore 169857, Singapore; [email protected] (M.T.); [email protected] (P.M.Y.) * Correspondence: [email protected] Received: 7 February 2020; Accepted: 24 February 2020; Published: 28 February 2020 Abstract: The estrogen-related receptor alpha (ESRRA) is an orphan nuclear receptor (NR) that significantly influences cellular metabolism. ESRRA is predominantly expressed in metabolically-active tissues and regulates the transcription of metabolic genes, including those involved in mitochondrial turnover and autophagy. Although ESRRA activity is well-characterized in several types of cancer, recent reports suggest that it also has an important role in metabolic diseases. This minireview focuses on the regulation of cellular metabolism and function by ESRRA and its potential as a target for the treatment of metabolic disorders. Keywords: estrogen-related receptor alpha; mitophagy; mitochondrial turnover; metabolic diseases; non-alcoholic fatty liver disease (NAFLD); adipogenesis; adaptive thermogenesis 1. Introduction When the estrogen-related receptor alpha (ESRRA) was first cloned, it was found to be a nuclear receptor (NR) that had DNA sequence homology to the estrogen receptor alpha (ESR1) [1]. There are several examples of estrogen-related receptor (ESRR) and estrogen-signaling cross-talk via mutual transcriptional regulation or reciprocal binding to each other’s response elements of common target genes in a context-specific manner [2,3]. -
GABPA Is a Master Regulator of Luminal Identity and Restrains Aggressive Diseases in Bladder Cancer
Cell Death & Differentiation (2020) 27:1862–1877 https://doi.org/10.1038/s41418-019-0466-7 ARTICLE GABPA is a master regulator of luminal identity and restrains aggressive diseases in bladder cancer 1,2,3 3,4 5 2,5 5 3 5 5 Yanxia Guo ● Xiaotian Yuan ● Kailin Li ● Mingkai Dai ● Lu Zhang ● Yujiao Wu ● Chao Sun ● Yuan Chen ● 5 6 3 1,2 1,2 3,7 Guanghui Cheng ● Cheng Liu ● Klas Strååt ● Feng Kong ● Shengtian Zhao ● Magnus Bjorkhölm ● Dawei Xu 3,7 Received: 3 June 2019 / Revised: 20 November 2019 / Accepted: 21 November 2019 / Published online: 4 December 2019 © The Author(s) 2019. This article is published with open access Abstract TERT promoter mutations occur in the majority of glioblastoma, bladder cancer (BC), and other malignancies while the ETS family transcription factors GABPA and its partner GABPB1 activate the mutant TERT promoter and telomerase in these tumors. GABPA depletion or the disruption of the GABPA/GABPB1 complex by knocking down GABPB1 was shown to inhibit telomerase, thereby eliminating the tumorigenic potential of glioblastoma cells. GABPA/B1 is thus suggested as a cancer therapeutic target. However, it is unclear about its role in BC. Here we unexpectedly observed that GABPA ablation 1234567890();,: 1234567890();,: inhibited TERT expression, but robustly increased proliferation, stem, and invasive phenotypes and cisplatin resistance in BC cells, while its overexpression exhibited opposite effects, and inhibited in vivo metastasizing in a xenograft transplant model. Mechanistically, GABPA directly activates the transcription of FoxA1 and GATA3, key transcription factors driving luminal differentiation of urothelial cells. Consistently, TCGA/GEO dataset analyses show that GABPA expression is correlated positively with luminal while negatively with basal signatures. -
SOMITOGENESIS in the CORN SNAKE Céline Gomez
SOMITOGENESIS IN THE CORN SNAKE Céline Gomez To cite this version: Céline Gomez. SOMITOGENESIS IN THE CORN SNAKE. Development Biology. Université Pierre et Marie Curie - Paris VI, 2007. English. NNT : 2007PA066439. tel-00807996 HAL Id: tel-00807996 https://tel.archives-ouvertes.fr/tel-00807996 Submitted on 4 Apr 2013 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. THESE DE DOCTORAT DE L’UNIVERSITE PIERRE ET MARIE CURIE Spécialité Biologie du Développement Présentée par Céline GOMEZ Pour obtenir le grade de DOCTEUR de l’UNIVERSITE PIERRE ET MARIE CURIE ETUDE DE LA SOMITOGENESE CHEZ LE SERPENT DES BLES Soutenue le 19 décembre 2007 Devant le jury composé de : Dr. Olivier POURQUIE: Directeur de thèse Dr. Guillaume BALAVOINE: Rapporteur Pr. Martin CATALA: Rapporteur Pr. Muriel UMBHAUER: Examinateur Pr. Denis DUBOULE: Examinateur 1 The Pierre et Marie Curie University SOMITOGENESIS IN THE CORN SNAKE A Thesis in Developmental Biology by Céline GOMEZ Submitted in Partial Fulfillement of the Requirements for the Degree of Doctor of Philosophy December 2007 2 ACKNOWLEDGMENTS I would like to heartily thank the Dr. Olivier Pourquié for his help in many ways. Thank you for having welcomed me in your team, whereas I was struggling to escape another laboratory, after having spent one year of my PhD. -
Increased HOXA5 Expression Provides a Selective Advantage for Gain of Whole Chromosome 7 in IDH Wild-Type Glioblastoma
Downloaded from genesdev.cshlp.org on May 11, 2018 - Published by Cold Spring Harbor Laboratory Press Increased HOXA5 expression provides a selective advantage for gain of whole chromosome 7 in IDH wild-type glioblastoma Patrick J. Cimino,1,2,17 Youngmi Kim,1,17 Hua-Jun Wu,3,4,5 Jes Alexander,1 Hans-Georg Wirsching,1,6 Frank Szulzewsky,1 Ken Pitter,7 Tatsuya Ozawa,1,8 Jiguang Wang,9,10,16 Julio Vazquez,11 Sonali Arora,1 Raul Rabadan,9,10 Ross Levine,12 Franziska Michor,3,4,5,13,14,15 and Eric C. Holland1 1Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA; 2Department of Pathology, Division of Neuropathology, University of Washington, Seattle, Washington 98104, USA; 3Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Harvard T.H. Chan School of Public Health, Boston, Massachusetts 02215, USA; 4Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts 02115, USA; 5Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA; 6Department of Neurology, University Hospital Zurich, Zurich 8091, Switzerland; 7Department of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA; 8Division of Brain Tumor Translational Research, National Cancer Center Research Institute, Tokyo 104-0045, Japan; 9Department of Biomedical Informatics, Columbia University, New York, New York 10027, USA; 10Department of Systems Biology, Columbia University, New York, -
Functional Genomics Atlas of Synovial Fibroblasts Defining Rheumatoid Arthritis
medRxiv preprint doi: https://doi.org/10.1101/2020.12.16.20248230; this version posted December 18, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Functional genomics atlas of synovial fibroblasts defining rheumatoid arthritis heritability Xiangyu Ge1*, Mojca Frank-Bertoncelj2*, Kerstin Klein2, Amanda Mcgovern1, Tadeja Kuret2,3, Miranda Houtman2, Blaž Burja2,3, Raphael Micheroli2, Miriam Marks4, Andrew Filer5,6, Christopher D. Buckley5,6,7, Gisela Orozco1, Oliver Distler2, Andrew P Morris1, Paul Martin1, Stephen Eyre1* & Caroline Ospelt2*,# 1Versus Arthritis Centre for Genetics and Genomics, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK 2Department of Rheumatology, Center of Experimental Rheumatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland 3Department of Rheumatology, University Medical Centre, Ljubljana, Slovenia 4Schulthess Klinik, Zurich, Switzerland 5Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK 6NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, University of Birmingham, Birmingham, UK 7Kennedy Institute of Rheumatology, University of Oxford Roosevelt Drive Headington Oxford UK *These authors contributed equally #corresponding author: [email protected] NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. 1 medRxiv preprint doi: https://doi.org/10.1101/2020.12.16.20248230; this version posted December 18, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.