The Complex Interplay Between MYC and the Molecular Circadian Clock in Cancer
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Circadian Clock in Cell Culture: II
The Journal of Neuroscience, January 1988, 8(i): 2230 Circadian Clock in Cell Culture: II. /n vitro Photic Entrainment of Melatonin Oscillation from Dissociated Chick Pineal Cells Linda M. Robertson and Joseph S. Takahashi Department of Neurobiology and Physiology, Northwestern University, Evanston, Illinois 60201 The avian pineal gland contains circadian oscillators that regulate the rhythmic synthesisof melatonin (Takahashi et al., regulate the rhythmic synthesis of melatonin. We have de- 1980; Menaker and Wisner, 1983; Takahashi and Menaker, veloped a flow-through cell culture system in order to begin 1984b). Previous work has shown that light exposure in vitro to study the cellular and molecular basis of this vertebrate can modulate N-acetyltransferase activity and melatonin pro- circadian oscillator. Pineal cell cultures express a circadian duction in chick pineal organ cultures (Deguchi, 1979a, 1981; oscillation of melatonin release for at least 5 cycles in con- Wainwright and Wainwright, 1980; Hamm et al., 1983; Taka- stant darkness with a period close to 24 hr. In all circadian hashi and Menaker, 1984b). Although acute exposure to light systems, light regulates the rhythm by the process of en- can suppressmelatonin synthesis, photic entrainment of cir- trainment that involves control of the phase and period of cadian rhythms in the pineal in vitro has not been definitively the circadian oscillator. In chick pineal cell cultures we have demonstrated. Preliminary work hassuggested that entrainment investigated the entraining effects of light in 2 ways: by shift- may occur; however, none of these studies demonstrated that ing the light-dark cycle in vitro and by measuring the phase- the steady-state phase of the oscillator was regulated by light shifting effects of single light pulses. -
The Rise and Fall of the Bovine Corpus Luteum
University of Nebraska Medical Center DigitalCommons@UNMC Theses & Dissertations Graduate Studies Spring 5-6-2017 The Rise and Fall of the Bovine Corpus Luteum Heather Talbott University of Nebraska Medical Center Follow this and additional works at: https://digitalcommons.unmc.edu/etd Part of the Biochemistry Commons, Molecular Biology Commons, and the Obstetrics and Gynecology Commons Recommended Citation Talbott, Heather, "The Rise and Fall of the Bovine Corpus Luteum" (2017). Theses & Dissertations. 207. https://digitalcommons.unmc.edu/etd/207 This Dissertation is brought to you for free and open access by the Graduate Studies at DigitalCommons@UNMC. It has been accepted for inclusion in Theses & Dissertations by an authorized administrator of DigitalCommons@UNMC. For more information, please contact [email protected]. THE RISE AND FALL OF THE BOVINE CORPUS LUTEUM by Heather Talbott A DISSERTATION Presented to the Faculty of the University of Nebraska Graduate College in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy Biochemistry and Molecular Biology Graduate Program Under the Supervision of Professor John S. Davis University of Nebraska Medical Center Omaha, Nebraska May, 2017 Supervisory Committee: Carol A. Casey, Ph.D. Andrea S. Cupp, Ph.D. Parmender P. Mehta, Ph.D. Justin L. Mott, Ph.D. i ACKNOWLEDGEMENTS This dissertation was supported by the Agriculture and Food Research Initiative from the USDA National Institute of Food and Agriculture (NIFA) Pre-doctoral award; University of Nebraska Medical Center Graduate Student Assistantship; University of Nebraska Medical Center Exceptional Incoming Graduate Student Award; the VA Nebraska-Western Iowa Health Care System Department of Veterans Affairs; and The Olson Center for Women’s Health, Department of Obstetrics and Gynecology, Nebraska Medical Center. -
MXD1 Localizes in the Nucleolus, Binds UBF and Impairs Rrna Synthesis
www.impactjournals.com/oncotarget/ Oncotarget, Vol. 7, No. 43 Research Paper MXD1 localizes in the nucleolus, binds UBF and impairs rRNA synthesis Maria del Carmen Lafita-Navarro1,3, Rosa Blanco1, Jorge Mata-Garrido2, Judit Liaño-Pons1, Olga Tapia2, Lucía García-Gutiérrez1, Eva García-Alegría1,4, María T. Berciano2, Miguel Lafarga2, Javier León1 1Instituto de Biomedicina y Biotecnología de Cantabria (IBBTEC), CSIC-Universidad de Cantabria, and Department of Molecular Biology, University of Cantabria, Santander, Spain 2Department of Anatomy and Cell Biology and Centro de Investigación en Red sobre Enfermedades Neurodegenerativas (CIBERNED), University of Cantabria-IDIVAL, Santander, Spain 3Present address: Department of Cell Biology, UT Southwestern Medical Center, Dallas, Texas, USA 4Present address: Stem Cell Hematopoiesis Group, Cancer Research UK Manchester Institute, University of Manchester, Manchester, United Kingdom Correspondence to: Javier León, email: [email protected] Keywords: MXD1, UBF, nucleolus, pre-rRNA, transcription regulation Received: June 20, 2016 Accepted: August 26, 2016 Published: August 31, 2016 ABSTRACT MXD1 is a protein that interacts with MAX, to form a repressive transcription factor. MXD1-MAX binds E-boxes. MXD1-MAX antagonizes the transcriptional activity of the MYC oncoprotein in most models. It has been reported that MYC overexpression leads to augmented RNA synthesis and ribosome biogenesis, which is a relevant activity in MYC-mediated tumorigenesis. Here we describe that MXD1, but not MYC or MNT, localizes to the nucleolus in a wide array of cell lines derived from different tissues (carcinoma, leukemia) as well as in embryonic stem cells. MXD1 also localizes in the nucleolus of primary tissue cells as neurons and Sertoli cells. -
Uncovering the Signaling Landscape Controlling Breast Cancer Cell Migration Identifies Novel Metastasis Driver Genes
ARTICLE https://doi.org/10.1038/s41467-019-11020-3 OPEN Uncovering the signaling landscape controlling breast cancer cell migration identifies novel metastasis driver genes Esmee Koedoot1,4, Michiel Fokkelman 1,4, Vasiliki-Maria Rogkoti1,4, Marcel Smid2, Iris van de Sandt1, Hans de Bont1, Chantal Pont1, Janna E. Klip1, Steven Wink 1, Mieke A. Timmermans2, Erik A.C. Wiemer2, Peter Stoilov3, John A. Foekens2, Sylvia E. Le Dévédec 1, John W.M. Martens 2 & Bob van de Water1 1234567890():,; Ttriple-negative breast cancer (TNBC) is an aggressive and highly metastatic breast cancer subtype. Enhanced TNBC cell motility is a prerequisite of TNBC cell dissemination. Here, we apply an imaging-based RNAi phenotypic cell migration screen using two highly motile TNBC cell lines (Hs578T and MDA-MB-231) to provide a repository of signaling determinants that functionally drive TNBC cell motility. We have screened ~4,200 target genes individually and discovered 133 and 113 migratory modulators of Hs578T and MDA-MB-231, respectively, which are linked to signaling networks predictive for breast cancer progression. The splicing factors PRPF4B and BUD31 and the transcription factor BPTF are essential for cancer cell migration, amplified in human primary breast tumors and associated with metastasis-free survival. Depletion of PRPF4B, BUD31 and BPTF causes primarily down regulation of genes involved in focal adhesion and ECM-interaction pathways. PRPF4B is essential for TNBC metastasis formation in vivo, making PRPF4B a candidate for further drug development. 1 Division of Drug Discovery and Safety, LACDR, Leiden University, Einsteinweg 55, Leiden 2333 CC, Netherlands. 2 Department of Medical Oncology and Cancer Genomics Netherlands, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam 3008 AE, Netherlands. -
Molecular Profile of Tumor-Specific CD8+ T Cell Hypofunction in a Transplantable Murine Cancer Model
Downloaded from http://www.jimmunol.org/ by guest on September 25, 2021 T + is online at: average * The Journal of Immunology , 34 of which you can access for free at: 2016; 197:1477-1488; Prepublished online 1 July from submission to initial decision 4 weeks from acceptance to publication 2016; doi: 10.4049/jimmunol.1600589 http://www.jimmunol.org/content/197/4/1477 Molecular Profile of Tumor-Specific CD8 Cell Hypofunction in a Transplantable Murine Cancer Model Katherine A. Waugh, Sonia M. Leach, Brandon L. Moore, Tullia C. Bruno, Jonathan D. Buhrman and Jill E. Slansky J Immunol cites 95 articles Submit online. Every submission reviewed by practicing scientists ? is published twice each month by Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts http://jimmunol.org/subscription Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html http://www.jimmunol.org/content/suppl/2016/07/01/jimmunol.160058 9.DCSupplemental This article http://www.jimmunol.org/content/197/4/1477.full#ref-list-1 Information about subscribing to The JI No Triage! Fast Publication! Rapid Reviews! 30 days* Why • • • Material References Permissions Email Alerts Subscription Supplementary The Journal of Immunology The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2016 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. This information is current as of September 25, 2021. The Journal of Immunology Molecular Profile of Tumor-Specific CD8+ T Cell Hypofunction in a Transplantable Murine Cancer Model Katherine A. -
A Genome-Wide Analysis of the ERF Gene Family in Sorghum
A genome-wide analysis of the ERF gene family in sorghum H.W. Yan, L. Hong, Y.Q. Zhou, H.Y. Jiang, S.W. Zhu, J. Fan and B.J. Cheng Key Laboratory of Crop Biology of Anhui Province, Anhui Agricultural University, Hefei, China Corresponding author: B.J. Cheng E-mail: [email protected] Genet. Mol. Res. 12 (2): 2038-2055 (2013) Received November 9, 2012 Accepted March 8, 2013 Published May 13, 2013 DOI http://dx.doi.org/10.4238/2013.May.13.1 ABSTRACT. The ethylene response factor (ERF) family are members of the APETALA2 (AP2)/ERF transcription factor superfamily; they are known to play an important role in plant adaptation to biotic and abiotic stress. ERF genes have been studied in Arabidopsis, rice, grape, and maize; however, there are few reports of ERF genes in sorghum. We identified 105 sorghum ERF (SbERF) genes, which were categorized into 12 groups (A-1 to A-6 and B-1 to B-6) based on their sequence similarity, and this new method of classification for ERF genes was then further characterized. A comprehensive bioinformatic analysis of SbERF genes was performed using a sorghum genomic database, to analyze the phylogeny of SbERF genes, identify other conserved motifs apart from the AP2/ERF domain, map SbERF genes to the 10 sorghum chromosomes, and determine the tissue-specific expression patterns of SbERF genes. Gene clustering indicates that SbERF genes were generated by tandem duplications. Comparison of SbERF genes with maize ERF homologs suggests lateral gene transfer between monocot species. These results can contribute to our understanting of Genetics and Molecular Research 12 (2): 2038-2055 (2013) ©FUNPEC-RP www.funpecrp.com.br Analysis of the ERF gene family in sorghum 2039 the evolution of the ERF gene family. -
UNIVERSITY of CALIFORNIA Los Angeles
UNIVERSITY OF CALIFORNIA Los Angeles Circadian Gene Networks In Bone Regeneration A thesis submitted in partial satisfaction of the requirements for the degree Master of Science in Oral Biology by Nathaniel Raphael Hassan 2012 ABSTRACT OF THESIS Circadian Gene Networks In Bone Regeneration By Nathaniel Raphael Hassan Master of Science in Oral Biology University of California, Los Angeles, 2012 Professor Ichiro Nishimura, Chair BACKGROUND: Previous studies suggested that vitamin D played a significant role in bone regeneration, facilitating the establishment of implant osseointegration. A whole genome microarray study further suggested that the vitamin D axis might involve circadian rhythm gene expression in the bone peripheral tissue. OBJECTIVES: To identify key gene networks involved with vitamin D receptor in the bone regeneration process and to explore any correlation with circadian rhythm gene expression in bone marrow mesenchymal stromal/stem cells (BMSC). METHODS: The available whole gene microarray data was analyzed using the weighted gene correlation network analysis (WGCNA) R package and Cytoscape software. Any gene expression correlation was examined for vitamin D receptor (VDR) as well as circadian rhythm ii genes. Separately, Per 1 luciferase transgenic Wistar rats were then applied for in vitro evaluation on BMSC circadian rhythm. Per1::luc BMSCs were seeded on 35mm dishes and forskolin-synchronized luminescence was recorded across different media conditions. The recording media included growth medium containing F12 (10% Fetal Bovine Serum, 1% Pen- Strep and antibiotic) supplemented with or without 1 nM 1,25D. Luminescence was also recorded in F12 growth medium containing bone differentiation factors (beta glycerophosphate, Ascorbic acid and Dexamethasone) supplemented with 0, 1 or 10 nM 1,25D. -
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. -
NPAS2 As a Transcriptional Regulator of Non-Rapid Eye Movement Sleep: Genotype and Sex Interactions
NPAS2 as a transcriptional regulator of non-rapid eye movement sleep: Genotype and sex interactions Paul Franken*†‡, Carol A. Dudley§, Sandi Jo Estill§, Monique Barakat*, Ryan Thomason¶, Bruce F. O’Hara¶, and Steven L. McKnight‡§ §Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390; *Department of Biological Sciences, Stanford University, Stanford, CA 94305; ¶Department of Biology, University of Kentucky, Lexington, KY 40506; and †Center for Integrative Genomics, University of Lausanne, CH-1015 Lausanne-Dorigny, Switzerland Contributed by Steven L. McKnight, March 13, 2006 Because the transcription factor neuronal Per-Arnt-Sim-type sig- delta frequency range is a sensitive marker of time spent awake (4, nal-sensor protein-domain protein 2 (NPAS2) acts both as a sensor 7) and local cortical activation (8) and is therefore widely used as and an effector of intracellular energy balance, and because sleep an index of NREMS need and intensity. is thought to correct an energy imbalance incurred during waking, The PAS-domain proteins, CLOCK, BMAL1, PERIOD-1 we examined NPAS2’s role in sleep homeostasis using npas2 (PER1), and PER2, play crucial roles in circadian rhythm gener- knockout (npas2؊/؊) mice. We found that, under conditions of ation (9). The NPAS2 paralog CLOCK, like NPAS2, can induce the increased sleep need, i.e., at the end of the active period or after transcription of per1, per2, cryptochrome-1 (cry1), and cry2. PER and sleep deprivation (SD), NPAS2 allows for sleep to occur at times CRY proteins, in turn, inhibit CLOCK- and NPAS2-induced when mice are normally awake. Lack of npas2 affected electroen- transcription, thereby closing a negative-feedback loop that is cephalogram activity of thalamocortical origin; during non-rapid thought to underlie circadian rhythm generation. -
A Molecular Perspective of Human Circadian Rhythm Disorders Nicolas Cermakian* , Diane B
Brain Research Reviews 42 (2003) 204–220 www.elsevier.com/locate/brainresrev Review A molecular perspective of human circadian rhythm disorders Nicolas Cermakian* , Diane B. Boivin Douglas Hospital Research Center, McGill University, 6875 LaSalle boulevard, Montreal, Quebec H4H 1R3, Canada Accepted 10 March 2003 Abstract A large number of physiological variables display 24-h or circadian rhythms. Genes dedicated to the generation and regulation of physiological circadian rhythms have now been identified in several species, including humans. These clock genes are involved in transcriptional regulatory feedback loops. The mutation of these genes in animals leads to abnormal rhythms or even to arrhythmicity in constant conditions. In this view, and given the similarities between the circadian system of humans and rodents, it is expected that mutations of clock genes in humans may give rise to health problems, in particular sleep and mood disorders. Here we first review the present knowledge of molecular mechanisms underlying circadian rhythmicity, and we then revisit human circadian rhythm syndromes in light of the molecular data. 2003 Elsevier Science B.V. All rights reserved. Theme: Neural basis of behavior Topic: Biological rhythms and sleep Keywords: Circadian rhythm; Clock gene; Sleep disorder; Suprachiasmatic nucleus Contents 1 . Introduction ............................................................................................................................................................................................ 205 -
Delayed Cryptochrome Degradation Asymmetrically Alters the Daily Rhythm in Suprachiasmatic Clock Neuron Excitability
7824 • The Journal of Neuroscience, August 16, 2017 • 37(33):7824–7836 Systems/Circuits Delayed Cryptochrome Degradation Asymmetrically Alters the Daily Rhythm in Suprachiasmatic Clock Neuron Excitability Sven Wegner,1 Mino D.C. Belle,1 Alun T.L. Hughes,1 Casey O. Diekman,2 and Hugh D. Piggins1 1Faculty of Biology, Medicine, and Health University of Manchester, Manchester, United Kingdom M13 9PT, and 2Department Mathematical Sciences, New Jersey Institute of Technology, Newark, New Jersey 07102 Suprachiasmatic nuclei (SCN) neurons contain an intracellular molecular circadian clock and the Cryptochromes (CRY1/2), key tran- scriptional repressors of this molecular apparatus, are subject to post-translational modification through ubiquitination and targeting for proteosomal degradation by the ubiquitin E3 ligase complex. Loss-of-function point mutations in a component of this ligase complex, Fbxl3, delay CRY1/2 degradation, reduce circadian rhythm strength, and lengthen the circadian period by ϳ2.5 h. The molecular clock drives circadian changes in the membrane properties of SCN neurons, but it is unclear how alterations in CRY1/2 stability affect SCN neurophysiology. Here we use male and female Afterhours mice which carry the circadian period lengthening loss-of-function Fbxl3Afh mutation and perform patch-clamp recordings from SCN brain slices across the projected day/night cycle. We find that the daily rhythm in membrane excitability in the ventral SCN (vSCN) was enhanced in amplitude and delayed in timing in Fbxl3Afh/Afh mice. At night, vSCN cells from Fbxl3Afh/Afh mice were more hyperpolarized, receiving more GABAergic input than their Fbxl3ϩ/ϩ counterparts. Unexpectedly, the progression to daytime hyperexcited states was slowed by Afh mutation, whereas the decline to hypoexcited states was accelerated. -
University of Birmingham Obeticholic Acid for the Treatment of Primary Biliary Cirrhosis
University of Birmingham Obeticholic acid for the treatment of primary biliary cirrhosis Trivedi, Palak J; Hirschfield, Gideon M; Gershwin, M Eric DOI: 10.1586/17512433.2015.1092381 License: None: All rights reserved Document Version Peer reviewed version Citation for published version (Harvard): Trivedi, PJ, Hirschfield, GM & Gershwin, ME 2016, 'Obeticholic acid for the treatment of primary biliary cirrhosis', Expert Review of Clinical Pharmacology, vol. 9, no. 1, pp. 13-26. https://doi.org/10.1586/17512433.2015.1092381 Link to publication on Research at Birmingham portal Publisher Rights Statement: Eligibility for repository: Checked on 29/2/2016 General rights Unless a licence is specified above, all rights (including copyright and moral rights) in this document are retained by the authors and/or the copyright holders. The express permission of the copyright holder must be obtained for any use of this material other than for purposes permitted by law. •Users may freely distribute the URL that is used to identify this publication. •Users may download and/or print one copy of the publication from the University of Birmingham research portal for the purpose of private study or non-commercial research. •User may use extracts from the document in line with the concept of ‘fair dealing’ under the Copyright, Designs and Patents Act 1988 (?) •Users may not further distribute the material nor use it for the purposes of commercial gain. Where a licence is displayed above, please note the terms and conditions of the licence govern your use of this document. When citing, please reference the published version. Take down policy While the University of Birmingham exercises care and attention in making items available there are rare occasions when an item has been uploaded in error or has been deemed to be commercially or otherwise sensitive.