DOCSLIB.ORG

Identification of Genetic Associations of SP110/MYBBP1A/RELA With

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Identification of Genetic Associations of SP110/MYBBP1A/RELA With Hum Genet (2013) 132:265–273 DOI 10.1007/s00439-012-1244-5 ORIGINAL INVESTIGATION Identification of genetic associations of SP110/MYBBP1A/RELA with pulmonary tuberculosis in the Chinese Han population Lei Cai • Shao-Li Deng • Li Liang • Hui Pan • Jia Zhou • Mei-Yan Wang • Jun Yue • Chun-Ling Wan • Guang He • Lin He Received: 18 June 2012 / Accepted: 17 October 2012 / Published online: 6 November 2012 Ó Springer-Verlag Berlin Heidelberg 2012 Abstract Genetic factors play important roles in the meta-analysis of rs9061 in East Asian populations showed development of tuberculosis (TB). SP110 is a promising that the rs9061 T allele conferred significant risk for TB candidate target for controlling TB infections. However, [P = 0.002, pooled odds ratio (OR), 1.24, 95 % confidence several studies associating SP110 single nucleotide poly- interval (CI) = 1.08–1.43]. The MYBBP1A GTCTTGGG morphisms (SNPs) with TB have yielded conflicting haplotype and haplotypes CGACCG/TGATTG within results. This may be partly resolved by studying other SP110 were found to be markedly and significantly asso- genes associated with SP110, such as MYBBP1A and ciated with TB (P = 2.00E-06, 5.00E-6 and 2.59E-4, RELA. Here, we genotyped 6 SP110 SNPs, 8 MYBBP1A respectively). Gene-based analysis also demonstrated that SNPs and 5 RELA SNPs in 702 Chinese pulmonary TB SP110 and MYBBP1A were each associated with TB patients and 425 healthy subjects using MassARRAY and (Pcor = 0.011 and 0.035, respectively). The logistic SNaPshot methods. Using SNP-based analysis with Bon- regression analysis results supported interactions between ferroni correction, rs3809849 in MYBBP1A [Pcorrected SP110 and MYBBP1A, indicating that subjects carrying a (cor) = 0.0038] and rs9061 in SP110 (Pcor = 0.019) were GC/CC genotype in MYBBP1A and CC genotype in SP110 found to be significantly associated with TB. Furthermore, possessed the high risk of developing TB (P = 1.74E-12). Our study suggests that a combination of SP110 and MYBBP1A gene polymorphisms may serve as a novel Electronic supplementary material The online version of this article (doi:10.1007/s00439-012-1244-5) contains supplementary material, which is available to authorized users. L. Cai (&) Á C.-L. Wan Á G. He Á L. He L. Liang Á J. Yue (&) Bio-X Center, Key Laboratory for the Genetics Shanghai Key Laboratory of Mycobacterium Tuberculosis, of Developmental and Neuropsychiatric Disorders Shanghai Pulmonary Hospital, Tongji University School (Ministry of Education), Shanghai Jiaotong University, of Medicine, 507 Zhengmin Rd, Shanghai 200433, China 800 Dongchuan Road, Shanghai 200030, China e-mail: [email protected] e-mail: [email protected] H. Pan L. Cai Á J. Zhou Department of Immunology and Infectious Diseases, Gordon Life Science Institute, 13784 Torrey Del Mar Drive, Harvard School of Public Health, Boston, USA San Diego, CA 92130, USA M.-Y. Wang L. Cai Á J. Zhou Fudan University School of Life Sciences and Technology, Key Laboratory of Systems Biomedicine, Advanced Institute of Translational Medicine, Shanghai, China Shanghai Centre for Systems Biomedicine, Shanghai Jiaotong University, Shanghai, China S.-L. Deng Department of Laboratory Medicine, Institute of Surgery Research, Daping Hospital, The Third Military Medical University, Chongqing, China 123 266 Hum Genet (2013) 132:265–273 marker for identifying the risk of developing TB in the structurally related inducible transcription factors (Bonizzi Chinese Han population. and Karin 2004). NF-jB, which is known to interact with IFN-c during TB development, regulates the expression of a wide variety of human genes, including factors regulating Introduction apoptosis and inducers of proliferation (Chan et al. 2001; Pahl 1999). Tuberculosis (TB) is a re-emerging disease epidemic in This study aimed to determine whether any genetic many parts of the world. As of 2010, China has the second- associations exist between SP110/MYBBP1A/RELA and largest number of incident cases worldwide (WHO 2011). pulmonary TB. We performed multiple analyses including Despite the availability of effective treatment over the past SNP-based, haplotype-based and gene-based analyses on an few decades, TB remains the second leading cause of association study using 1,127 Chinese subjects. The SNP- deaths from infectious diseases worldwide (WHO 2011). based analysis results were further evaluated using meta- Multiple factors contribute to the risk of infection and analysis and protein 3D structure analysis. The logistic development of TB, including host–pathogen interactions regression analysis was performed to evaluate the gene– and environmental factors. Furthermore, there is evidence gene interaction. Our work suggests a combination of SP110 to indicate that the risk of developing TB in human is and MYBBP1A gene polymorphisms is significantly asso- strongly influenced by genetic factors (Bellamy 2003; ciated with TB, which provides an effective novel bio- Cooke and Hill 2001). marker for TB susceptibility in the Chinese Han population. SP110 is emerging as a promising candidate for its mouse homologue controlling Mycobacterium tuberculosis (MTB) infections (Pan et al. 2005). SP110 contains Materials and methods nuclear-characterized structural motifs, such as the chro- matin-interacting SAND domain and the LXXLL nuclear Study subjects hormone interaction motif. Following induction by inter- feron-a and interferon-c, SP110 is preferentially expressed Patients with TB were recruited from Shanghai Pulmonary in leukocytes and spleen cells (Bloch et al. 2000). The Hospital and Chongqing Daping Hospital in southern mouse homologue of SP110 has been found to be strongly China between June 2009 and September 2011. All patients expressed in lung lesions from TB and macrophages of were clinically and radiologically diagnosed with pul- susceptibility to tuberculosis 1 (sst1)-resistant mice, but not monary TB; sputum smears and cultures were used to expressed in sst1-susceptible mice. Moreover, mouse confirm M. tuberculosis infection. All patients were HIV- SP110 has the ability to control MTB growth in macro- negative and none presented with other infectious diseases phages and induce apoptosis in infected macrophage cells or immunosuppressive conditions. The characteristics of (Pan et al. 2005). study subjects were listed in Table 1. Healthy control Several SNP-based studies have reported associations subjects were recruited from blood donors, who had neg- between SP110 and susceptibility to pulmonary TB in ative tuberculin skin tests with indurations of \5mmon different populations, however, these have yielded con- the fourth day after inoculation, no history of TB and no flicting results (Babb et al. 2007; Cong et al. 2010; Liang evidence of prior TB noted in chest radiographies. Both et al. 2011; Png et al. 2012; Szeszko et al. 2007; Tosh et al. cases and controls were selected with following procedures 2006). We note that inconsistencies arising from popula- to exclude the possibility of immunosuppressive condi- tion differences are more readily resolved by use of a gene- tions. Firstly, they were investigated that they had no his- based or multi-gene-based approach rather than using tory of an immunosuppressive condition (i.e., human either a SNP-based or a haplotype-based approach (Neale immunodeficiency virus (HIV) infection, leukemia, lym- and Sham 2004). Thus, these conflicting results may be phoma, diabetes mellitus, or renal failure) or of taking partly resolved by studying other genes associated with immunosuppressive drugs within the last 3 months. Sec- SP110, such as MYBBP1A and RELA, which have not been ondly, HIV antibody and CD4? cell counts were assessed investigated in previous works. MYBBP1A has been to exclude HIV infection. Thirdly, these CD3?, CD4? and reported to bind with SP110 in mice, and it has been CD8? cell counts were assessed to exclude cell immune demonstrated that SP110 induces cells apoptosis by inter- deficiency. Finally, measurements of quantitative immu- acting with MYBBP1A (Cai et al. 2010). MYBBP1A is a noglobulin levels, including IgG, IgA, and IgM, and transcription factor critical for hematopoietic cell proli- complement levels were used to exclude antibody and feration and differentiation and is involved in the NF-jB complement deficiency. Informed consent was obtained pathway through its ability to bind with RELA (Owen et al. from all TB patients and controls participating in this 2007). RELA is a member of the NF-jB family of study. This study protocol was approved by the Ethics 123 Hum Genet (2013) 132:265–273 267 Table 1 Characteristics of subjects in this study using 5.4 pmol of each primer extension probe, 50 mmol Characteristics Cases Controls of iPlex Termination Mix, and 0.5 U of iPLEX enzyme (Sequenom). The extension reactions were carried out at Number 702 425 94 °C for 30 s and then 94 °C for 5 s, followed by 5 cycles at Age, mean ± SD (years) 40.0 ± 15.6 41.2 ± 17.7 52 °C for 5 s and 80 °C for 5 s for a total of 40 cycles and Male (%) 68.2 66.7 finally at 72 °C for 3 min. Purified extension reaction prod- Number of patients with/without fever 254/448 ucts with cation exchange resin were spotted onto Spectro- Number of patients with cavities in 369 CHIPs and determined by MALDI-TOF mass spectrometry. chest radiograph The SNP rs9061 and two other SNPs (rs11556887 and SD standard deviation rs1135791) investigated to evaluate the genotyping above were studied using the SNaPshot Kit (Applied Biosystems, Committee of Shanghai Pulmonary Hospital and Chongq- Inc.).
Load more

Recommended publications
  • Grant Application Form Please Complete the Following Form for IETF
    ©2007 IETF Grant Application Form Please complete the following form for IETF grant applications. This form and all the attachments below must be combined into one document before submitting electronically. Grant submissions will not be accepted otherwise. Attachments Required 1. Specific aims of the proposal (1 page maximum). 2. Rationale of the proposal and relevance to essential tremor (1-2 pages maximum). 3. Preliminary data, if available should be incorporated into the Rationale/Relevance section. Preliminary data are not required for a proposal. However, if preliminary data are referred to in the proposal rationale, or have been used to formulate the hypotheses to be tested, such information must be formally presented in this section. 4. Research methods and procedures (1-2 pages maximum). 5. Anticipated results (half-page maximum). 6. Detailed budget and justification (1 page maximum). 7. Biographic sketch of principal investigator and all professional personnel participating in the project (standard NIH format, including biosketch and other support). 8. Copies of relevant abstracts and/or articles that have been published, are in press, or have been submitted for publication. 9. Completed conflict of interest questionnaire. Project Title: ____________________________________________________________________________ Sponsoring Institution: ____________________________________________________________________ Principal Investigator: Last Name: _______________________________ First Name: ______________________ Middle Initial: __ Degree(s):
    [Show full text]
  • Open Data for Differential Network Analysis in Glioma
    International Journal of Molecular Sciences Article Open Data for Differential Network Analysis in Glioma , Claire Jean-Quartier * y , Fleur Jeanquartier y and Andreas Holzinger Holzinger Group HCI-KDD, Institute for Medical Informatics, Statistics and Documentation, Medical University Graz, Auenbruggerplatz 2/V, 8036 Graz, Austria; [email protected] (F.J.); [email protected] (A.H.) * Correspondence: [email protected] These authors contributed equally to this work. y Received: 27 October 2019; Accepted: 3 January 2020; Published: 15 January 2020 Abstract: The complexity of cancer diseases demands bioinformatic techniques and translational research based on big data and personalized medicine. Open data enables researchers to accelerate cancer studies, save resources and foster collaboration. Several tools and programming approaches are available for analyzing data, including annotation, clustering, comparison and extrapolation, merging, enrichment, functional association and statistics. We exploit openly available data via cancer gene expression analysis, we apply refinement as well as enrichment analysis via gene ontology and conclude with graph-based visualization of involved protein interaction networks as a basis for signaling. The different databases allowed for the construction of huge networks or specified ones consisting of high-confidence interactions only. Several genes associated to glioma were isolated via a network analysis from top hub nodes as well as from an outlier analysis. The latter approach highlights a mitogen-activated protein kinase next to a member of histondeacetylases and a protein phosphatase as genes uncommonly associated with glioma. Cluster analysis from top hub nodes lists several identified glioma-associated gene products to function within protein complexes, including epidermal growth factors as well as cell cycle proteins or RAS proto-oncogenes.
    [Show full text]
  • Spatial Localization of Genes Determined by Intranu- Clear DNA Fragmentation with the Fusion Proteins Lamin KRED and Histone
    Int. J. Med. Sci. 2013, Vol. 10 1136 Ivyspring International Publisher International Journal of Medical Sciences 2013; 10(9):1136-1148. doi: 10.7150/ijms.6121 Research Paper Spatial Localization of Genes Determined by Intranu- clear DNA Fragmentation with the Fusion Proteins Lamin KRED and Histone KRED und Visible Light Waldemar Waldeck1, Gabriele Mueller1, Karl-Heinz Glatting3, Agnes Hotz-Wagenblatt3, Nicolle Diessl4, Sasithorn Chotewutmonti4, Jörg Langowski1, Wolfhard Semmler2, Manfred Wiessler2 and Klaus Braun2 1. German Cancer Research Center, Dept. of Biophysics of Macromolecules, INF 580, D-69120 Heidelberg, Germany; 2. German Cancer Research Center, Dept. of Medical Physics in Radiology, INF 280, D-69120 Heidelberg, Germany; 3. German Cancer Research Center, Genomics Proteomics Core Facility HUSAR Bioinformatics Lab, INF 580, D-69120 Heidelberg, Ger- many; 4. German Cancer Research Center, Genomics and Proteomics Core Facility High Throughput Sequencing, INF 580, D-69120 Heidelberg, Germany. Corresponding author: Dr. Klaus Braun, German Cancer Research Center (DKFZ), Dept. of Medical Physics in Radiology, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany. Phone: +49 6221-42 3329 Fax: +49 6221-42 3326 e-mail: [email protected]. © Ivyspring International Publisher. This is an open-access article distributed under the terms of the Creative Commons License (http://creativecommons.org/ licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. Received: 2013.02.22; Accepted: 2013.06.06; Published: 2013.07.07 Abstract The highly organized DNA architecture inside of the nuclei of cells is accepted in the scientific world. In the human genome about 3 billion nucleotides are organized as chromatin in the cell nucleus.
    [Show full text]
  • A High-Throughput Approach to Uncover Novel Roles of APOBEC2, a Functional Orphan of the AID/APOBEC Family
    Rockefeller University Digital Commons @ RU Student Theses and Dissertations 2018 A High-Throughput Approach to Uncover Novel Roles of APOBEC2, a Functional Orphan of the AID/APOBEC Family Linda Molla Follow this and additional works at: https://digitalcommons.rockefeller.edu/ student_theses_and_dissertations Part of the Life Sciences Commons A HIGH-THROUGHPUT APPROACH TO UNCOVER NOVEL ROLES OF APOBEC2, A FUNCTIONAL ORPHAN OF THE AID/APOBEC FAMILY A Thesis Presented to the Faculty of The Rockefeller University in Partial Fulfillment of the Requirements for the degree of Doctor of Philosophy by Linda Molla June 2018 © Copyright by Linda Molla 2018 A HIGH-THROUGHPUT APPROACH TO UNCOVER NOVEL ROLES OF APOBEC2, A FUNCTIONAL ORPHAN OF THE AID/APOBEC FAMILY Linda Molla, Ph.D. The Rockefeller University 2018 APOBEC2 is a member of the AID/APOBEC cytidine deaminase family of proteins. Unlike most of AID/APOBEC, however, APOBEC2’s function remains elusive. Previous research has implicated APOBEC2 in diverse organisms and cellular processes such as muscle biology (in Mus musculus), regeneration (in Danio rerio), and development (in Xenopus laevis). APOBEC2 has also been implicated in cancer. However the enzymatic activity, substrate or physiological target(s) of APOBEC2 are unknown. For this thesis, I have combined Next Generation Sequencing (NGS) techniques with state-of-the-art molecular biology to determine the physiological targets of APOBEC2. Using a cell culture muscle differentiation system, and RNA sequencing (RNA-Seq) by polyA capture, I demonstrated that unlike the AID/APOBEC family member APOBEC1, APOBEC2 is not an RNA editor. Using the same system combined with enhanced Reduced Representation Bisulfite Sequencing (eRRBS) analyses I showed that, unlike the AID/APOBEC family member AID, APOBEC2 does not act as a 5-methyl-C deaminase.
    [Show full text]
  • Toward Understanding the Role of P53 in Cardiovascular Diseases
    J. Biomedical Science and Engineering, 2013, 6, 209-212 JBiSE http://dx.doi.org/10.4236/jbise.2013.62A025 Published Online February 2013 (http://www.scirp.org/journal/jbise/) Toward understanding the role of p53 in cardiovascular diseases Mohanalatha Chandrasekharan1, Silvia Vasquez2, Rajesh Kumar Galimudi3, Prashanth Suravajhala1 1Bioclues.org, IKP Knowledge Park, Secunderabad, India 2Instituto Peruano de Energía Nuclear, Centro Nuclear RACSO, Lima, Perú 3Department of Genetics, Osmania University, Hyderabad, India Email: [email protected], [email protected], [email protected], [email protected] Received 14 November 2012; revised 15 December 2012; accepted 22 December 2012 ABSTRACT hypertrophy to heart failure through the suppression of hypoxia inducible factor-1 (HIF-1), which regulates an- Tumour suppressor protein 53 (TP53 or simply p53) giogenesis in the hypertrophied heart. In addition, as p53 is a well known protein linked to apoptosis, cell sig- is known to promote apoptosis, which in turn is involved nalling, cascading and several myriad functions in in heart failure, p53 might be a key molecule in trigger- cells. Many diseases are linked to p53 though analysis ing the development of heart failure from multiple me- show only 216 interaction partners. Whether p53 chanisms [5,6]. While p53 can modulate the activity and plays an important role in cardiovascular diseases expression of some other proteins have been recently (CVD) remains uncertain. Through this bioinfor- studied, whether or not there are potentially beneficial matical analysis, we propose that p53 might play a effects remains to be understood. The actions of the ag- major role in CVD whilst being linked to Hypoxia ing proteins on the CVD have been well studied [7] with and Lupus.
    [Show full text]
  • (MYBBP1A) Is Essential for Early Embryonic Development, Controls
    Myb-binding protein 1A (MYBBP1A) is essential for early embryonic development, controls cell cycle and mitosis, and acts as a tumor suppressor Silvia Mori, Rosa Bernardi, Audrey Laurent, Massimo Resnati, Ambra Crippa, Arianna Gabrieli, Rebecca Keough, Thomas J Gonda, Francesco Blasi To cite this version: Silvia Mori, Rosa Bernardi, Audrey Laurent, Massimo Resnati, Ambra Crippa, et al.. Myb-binding protein 1A (MYBBP1A) is essential for early embryonic development, controls cell cycle and mito- sis, and acts as a tumor suppressor. PLoS ONE, Public Library of Science, 2012, 7 (10), pp.1-14. 10.1371/journal.pone.0039723. hal-02181057 HAL Id: hal-02181057 https://hal.archives-ouvertes.fr/hal-02181057 Submitted on 11 Jul 2019 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. Distributed under a Creative Commons Attribution| 4.0 International License Myb-Binding Protein 1A (MYBBP1A) Is Essential for Early Embryonic Development, Controls Cell Cycle and Mitosis, and Acts as a Tumor Suppressor Silvia Mori1, Rosa Bernardi1,2, Audrey Laurent3, Massimo Resnati2,
    [Show full text]
  • Coexpression Networks Based on Natural Variation in Human Gene Expression at Baseline and Under Stress
    University of Pennsylvania ScholarlyCommons Publicly Accessible Penn Dissertations Fall 2010 Coexpression Networks Based on Natural Variation in Human Gene Expression at Baseline and Under Stress Renuka Nayak University of Pennsylvania, [email protected] Follow this and additional works at: https://repository.upenn.edu/edissertations Part of the Computational Biology Commons, and the Genomics Commons Recommended Citation Nayak, Renuka, "Coexpression Networks Based on Natural Variation in Human Gene Expression at Baseline and Under Stress" (2010). Publicly Accessible Penn Dissertations. 1559. https://repository.upenn.edu/edissertations/1559 This paper is posted at ScholarlyCommons. https://repository.upenn.edu/edissertations/1559 For more information, please contact [email protected]. Coexpression Networks Based on Natural Variation in Human Gene Expression at Baseline and Under Stress Abstract Genes interact in networks to orchestrate cellular processes. Here, we used coexpression networks based on natural variation in gene expression to study the functions and interactions of human genes. We asked how these networks change in response to stress. First, we studied human coexpression networks at baseline. We constructed networks by identifying correlations in expression levels of 8.9 million gene pairs in immortalized B cells from 295 individuals comprising three independent samples. The resulting networks allowed us to infer interactions between biological processes. We used the network to predict the functions of poorly-characterized human genes, and provided some experimental support. Examining genes implicated in disease, we found that IFIH1, a diabetes susceptibility gene, interacts with YES1, which affects glucose transport. Genes predisposing to the same diseases are clustered non-randomly in the network, suggesting that the network may be used to identify candidate genes that influence disease susceptibility.
    [Show full text]
  • Genome-Wide SNP-Based Linkage Analysis of Tuberculosis in Thais
    Genes and Immunity (2009) 10, 77–83 & 2009 Macmillan Publishers Limited All rights reserved 1466-4879/09 $32.00 www.nature.com/gene ORIGINAL ARTICLE Genome-wide SNP-based linkage analysis of tuberculosis in Thais S Mahasirimongkol1,2, H Yanai2,3, N Nishida4, C Ridruechai5, I Matsushita6, J Ohashi4, S Summanapan7, N Yamada2, S Moolphate2, C Chuchotaworn8, A Chaiprasert9, W Manosuthi10, P Kantipong11, S Kanitwittaya12, T Sura13, S Khusmith5, K Tokunaga4, P Sawanpanyalert1 and N Keicho6 1Medical Genetic Section, National Institute of Health, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand; 2TB/HIV Research Project, Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Chiang Rai, Thailand; 3Center for Collaborative Research and Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan; 4Department of Human Genetics, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan; 5Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; 6Department of Respiratory Diseases, Research Institute, International Medical Center of Japan, Shinjuku-ku, Tokyo, Japan; 7Chiang Rai Provincial Health Office, Ministry of Public Health, Chiang Rai, Thailand; 8Chest Disease Institute, Department of Medical Services, Ministry of Public Health, Nonthaburi, Thailand; 9Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; 10Bamrasnaradura Infectious Diseases Institute, Ministry of Public Health, Nonthaburi, Thailand; 11Chiang Rai Regional Hospital, Ministry of Public Health, Chiang Rai, Thailand; 12Chiang Rai Regional Medical Sciences Center, Department of Medical Sciences, Ministry of Public Health, Chiang Rai, Thailand and 13Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand Tuberculosis, a potentially fatal infectious disease, affects millions of individuals annually worldwide.
    [Show full text]
  • Identification and Characterisation of Mybbp1a As a Regulator of Rrna Synthesis
    Dissertation zur Erlangung des Doktorgrades der Fakultät für Biologie der Ludwig-Maximilians-Universität München Identification and Characterisation of Mybbp1a as a Regulator of rRNA Synthesis Julia Hochstatter aus München 2011 Ehrenwörtliche Versicherung Ich versichere hiermit ehrenwörtlich, dass die vorgelegte Dissertation von mir selbständig und ohne unerlaubte Hilfe angefertigt ist. München, den 01.06.2011 Julia Hochstatter Erklärung Hiermit erkläre ich, dass die Dissertation nicht ganz oder in wesentlichen Teilen einer anderen Prüfungskommission vorgelegt worden ist. Ich habe mich nicht anderweitig einer Doktorprüfung unterzogen und ich habe zu keinem früheren Zeitpunkt versucht, eine Dissertation einzureichen oder mich der Doktorprüfung zu unterziehen. München, den 01.06.2011 Julia Hochstatter Dissertation eingereicht am: 01. Juni 2011 1. Gutachter: Prof. Dr. Peter Becker 2. Gutachterin: Prof. Dr. Elisabeth Weiß Tag der mündlichen Prüfung: 18.07.2011 Veröffentlichungen in Fachzeitschriften Teile bzw. Beiträge der vorliegenden Arbeit wurden in folgenden Artikel veröffentlicht: Julia Hochstatter, Attila Németh, Michael Hölzel, Michaela Rohrmoser, Lothar Schermelleh, Heinrich Leonhardt, Rebecca Keough, Thomas J. Gonda, Axel Imhof, Dirk Eick and Gernot Längst Mybbp1a is Involved in the Regulation of rRNA Gene Transcription and pre-rRNA Processing submitted Hölzel M, Orban M, Hochstatter J, Rohrmoser M, Harasim T, Malamoussi A, Kremmer E, Längst G, Eick D. Defects in 18 S or 28 S rRNA processing activate the p53 pathway. J Biol Chem. 2010 Feb 26;285(9):6364-70. Epub 2010 Jan 7. Für Moritz und Franz Acknowledgements First, I would like to thank my supervisor Prof. Dr. Gernot Längst for giving me the opportunity to work on an exciting project in a great team.
    [Show full text]
  • Multiple Myeloma–Associated Chromosomal Translocation Activates Orphan Snorna ACA11 to Suppress Oxidative Stress
    Multiple myeloma–associated chromosomal translocation activates orphan snoRNA ACA11 to suppress oxidative stress Liang Chu, … , Ravi Vij, Michael H. Tomasson J Clin Invest. 2012;122(8):2793-2806. https://doi.org/10.1172/JCI63051. Research Article The histone methyltransferase WHSC1 (also known as MMSET) is overexpressed in multiple myeloma (MM) as a result of the t(4;14) chromosomal translocation and in a broad variety of other cancers by unclear mechanisms. Overexpression of WHSC1 did not transform wild-type or tumor-prone primary hematopoietic cells. We found that ACA11, an orphan box H/ACA class small nucleolar RNA (snoRNA) encoded within an intron of WHSC1, was highly expressed in t(4;14)-positive MM and other cancers. ACA11 localized to nucleoli and bound what we believe to be a novel small nuclear ribonucleoprotein (snRNP) complex composed of several proteins involved in postsplicing intron complexes. RNA targets of this uncharacterized snRNP included snoRNA intermediates hosted within ribosomal protein (RP) genes, and an RP gene signature was strongly associated with t(4;14) in patients with MM. Expression of ACA11 was sufficient to downregulate RP genes and other snoRNAs implicated in the control of oxidative stress. ACA11 suppressed oxidative stress, afforded resistance to chemotherapy, and increased the proliferation of MM cells, demonstrating that ACA11 is a critical target of the t(4;14) translocation in MM and suggesting an oncogenic role in other cancers as well. Find the latest version: https://jci.me/63051/pdf Related Commentary, page 2765 Research article Multiple myeloma–associated chromosomal translocation activates orphan snoRNA ACA11 to suppress oxidative stress Liang Chu,1 Mack Y.
    [Show full text]
  • Latest/ Static/Widget/Autocomplete/Js/Mygene
    MyGene.info Documentation Release 3.0 Chunlei Wu Jul 26, 2021 Contents 1 Introduction 1 2 What’s new in v3 API 3 3 Quick start 5 3.1 Gene query service............................................5 3.1.1 URL...............................................5 3.1.2 Examples............................................5 3.1.3 To learn more..........................................5 3.2 Gene annotation service.........................................6 3.2.1 URL...............................................6 3.2.2 Examples............................................6 3.2.3 To learn more..........................................6 4 Documentation 7 4.1 Migration from v2 API..........................................7 4.1.1 URL change...........................................7 4.1.2 Returned Objects........................................7 4.2 Gene annotation data........................................... 12 4.2.1 Data sources........................................... 12 4.2.2 Gene object........................................... 12 4.2.3 _id field............................................. 13 4.2.4 _score field........................................... 13 4.2.5 Species............................................. 13 4.2.6 Genome assemblies....................................... 13 4.2.7 Available fields......................................... 14 4.3 Data release notes............................................ 14 4.3.1 MyGene Releases........................................ 14 4.4 Gene query service...........................................
    [Show full text]
  • Bothrops Jararaca Snake Venom Modulates Key Cancer-Related Proteins in Breast Tumor Cell Lines
    toxins Article Bothrops Jararaca Snake Venom Modulates Key Cancer-Related Proteins in Breast Tumor Cell Lines Carolina Yukiko Kisaki 1, Stephanie Santos Suehiro Arcos 1, Fabio Montoni 1, Wellington da Silva Santos 1, Hamida Macêdo Calacina 1, Ismael Feitosa Lima 1, Daniela Cajado-Carvalho 1 , Emer Suavinho Ferro 2 , Milton Yutaka Nishiyama-Jr 1,* and Leo Kei Iwai 1,* 1 Laboratory of Applied Toxinology (LETA) and Center of Toxins, Immune-Response and Cell Signaling (CeTICS), Butantan Institute, São Paulo 05503-900, Brazil; [email protected] (C.Y.K.); [email protected] (S.S.S.A.); [email protected] (F.M.); [email protected] (W.d.S.S.); [email protected] (H.M.C.); [email protected] (I.F.L.); [email protected] (D.C.-C.) 2 Department of Pharmacology, Biomedical Sciences Institute (ICB), University of São Paulo (USP), São Paulo 05508-000, Brazil; [email protected] * Correspondence: [email protected] (M.Y.N.-J.); [email protected] (L.K.I.) Abstract: Cancer is characterized by the development of abnormal cells that divide in an uncontrolled way and may spread into other tissues where they may infiltrate and destroy normal body tissue. Several previous reports have described biochemical anti-tumorigenic properties of crude snake venom or its components, including their capability of inhibiting cell proliferation and promoting cell death. However, to the best of our knowledge, there is no work describing cancer cell pro- teomic changes following treatment with snake venoms. In this work we describe the quantitative changes in proteomics of MCF7 and MDA-MB-231 breast tumor cell lines following treatment with Citation: Kisaki, C.Y.; Arcos, S.S.S.; Bothrops jararaca snake venom, as well as the functional implications of the proteomic changes.
    [Show full text]