DOCSLIB.ORG

Pathway Antigen-Processing and Peptide-Loading

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Pathway Antigen-Processing and Peptide-Loading PRDM1/BLIMP-1 Modulates IFN-γ -Dependent Control of the MHC Class I Antigen-Processing and Peptide-Loading Pathway This information is current as of September 26, 2021. Gina M. Doody, Sophie Stephenson, Charles McManamy and Reuben M. Tooze J Immunol 2007; 179:7614-7623; ; doi: 10.4049/jimmunol.179.11.7614 http://www.jimmunol.org/content/179/11/7614 Downloaded from References This article cites 67 articles, 21 of which you can access for free at: http://www.jimmunol.org/content/179/11/7614.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication by guest on September 26, 2021 *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2007 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology PRDM1/BLIMP-1 Modulates IFN-␥-Dependent Control of the MHC Class I Antigen-Processing and Peptide-Loading Pathway1 Gina M. Doody,* Sophie Stephenson,* Charles McManamy,† and Reuben M. Tooze2* A diverse spectrum of unique peptide-MHC class I complexes guides CD8 T cell responses toward viral or stress-induced Ags. Multiple components are required to process Ag and facilitate peptide loading in the endoplasmic reticulum. IFN-␥, a potent proinflammatory cytokine, markedly up-regulates transcription of genes involved in MHC class I assembly. Physiological mech- anisms which counteract this response are poorly defined. We demonstrate that promoters of functionally linked genes on this pathway contain conserved regulatory elements that allow antagonistic regulation by IFN-␥ and the transcription factor B lymphocyte-induced maturation protein-1 (also known as PR domain-containing 1, with ZNF domain (PRDM1)). Repression of ERAP1, TAPASIN, MECL1, and LMP7 by PRDM1 results in failure to up-regulate surface MHC class I in response to IFN-␥ in Downloaded from human cell lines. Using the sea urchin prdm1 ortholog, we demonstrate that the capacity of PRDM1 to repress the IFN response of such promoters is evolutionarily ancient and that dependence on the precise IFN regulatory factor element sequence is highly conserved. This indicates that the functional interaction between PRDM1 and IFN-regulated pathways antedates the evolution of the adaptive immune system and the MHC, and identifies a unique role for PRDM1 as a key regulator of Ag presentation by MHC class I. The Journal of Immunology, 2007, 179: 7614–7623. http://www.jimmunol.org/ he MHC class I system is first evident early in the evo- (MECL1), to generate the immunoproteasome (3). It acts to facil- lution of jawed vertebrates at the inception of the “adap- itate the transport of such peptides into the endoplasmic reticulum T tive” or “anticipatory” type immune response (1). The (ER), where the MHC class I peptide complex is assembled, by MHC class I Ag-processing and -presentation pathways co-opted inducing the expression of the peptide transporters TAP1 and and adapted existing cellular machinery to allow the sampling of TAP2 (4, 5). It enhances the expression of the TAP-associated proteins during normal and altered cellular conditions and subse- chaperone protein TAPASIN which facilitates peptide loading into quent presentation to CD8-restricted T cells (2). The immune sys- the MHC class I-binding groove (6, 7) and ER amino peptidase 1 tem has evolved the ability to change the pattern of peptide pre- (ERAP1) (8, 9), which is responsible for trimming peptides to fit by guest on September 26, 2021 sentation in response to inflammatory cues by adapting the cellular the groove, a function vital to the generation of the mature peptide machinery engaged in the generation of the peptide repertoire. For repertoire (10). example, in the context of viral infection or inflammation, IFN-␥ The cumulative effects of IFN-␥ therefore provide the cell with modulates not only the transcription of the MHC class I genes, but both qualitatively different peptides and a quantitative increase in also multiple components of the Ag-processing and -loading path- surface MHC expression with which to elicit T cell activation. ways. IFN-␥ enhances the generation of peptides of an appropriate Changes in the peptide repertoire can lead to inappropriate de- length for presentation by inducing the expression of alternate pro- structive immune responses and contribute to the initiation of au- 3 teasome components, large multifunctional peptidase 2 (LMP2) , toimmune disease (11). The response to IFN-␥ provides a para- LMP7, and multicatalytic endopeptidase complex subunit-1 digm for the transcriptional control of MHC class I-dependent Ag presentation (3). Although the mechanisms for activation have *Section of Experimental Haematology, Leeds Institute of Molecular Medicine, and been extensively studied, the endogenous factors mediating oppos- †Academic Unit of Oncology and Haematology, Haematological Malignancy Diag- ing or repressive effects on IFN-␥-induced transcription to main- nostic Service, University of Leeds, Leeds, United Kingdom tain normal levels of MHC class I expression and unaltered peptide Received for publication February 16, 2007. Accepted for publication September 11, 2007. repertoires are ill-defined. Nevertheless, the tight control inherent in other aspects of the immune response suggests that these are The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance likely to exist. with 18 U.S.C. Section 1734 solely to indicate this fact. B lymphocyte-induced maturation protein-1 (BLIMP-1), 1 This work was supported by a Medical Research Council Clinician Scientist Fel- which is also known as PR domain-containing 1, with ZNF lowship (to R.M.T). domain (PRDM1), is an evolutionarily conserved transcrip- 2 Address correspondence and reprint requests to Dr. Reuben M. Tooze, Section of tional repressor of the Kru¨ppel family of zinc finger proteins Experimental Haematology, Leeds Institute of Molecular Medicine, Wellcome Trust Brenner Building, St. James’s University Hospital, Beckett Street, Leeds LS9 7TF, (12–15), which acts both through direct competition for pro- U.K. E-mail address: [email protected] moter occupancy, and by recruiting epigenetic modifiers (16– 3 Abbreviations used in this paper: LMP, large multifunctional peptidase; MECL-1, 20). It is best known as a regulator of terminal B cell differen- multicatalytic endopeptidase complex subunit-1; ER, endoplasmic reticulum; ERAP1, ER amino peptidase-1; BLIMP-1, B lymphocyte-induced maturation protein-1; tiation (21, 22), but additional roles for PRDM1 have also been PRDM1, PR domain-containing 1, with ZNF domain; IRF, IFN regulatory factor; identified in the control of T cell (23, 24), macrophage (25), and IRF-E, IRF element; ChIP, chromatin immunoprecipitation; EGFP, enhanced GFP; sebaceous gland differentiation (26). The original identification siRNA, short interfering RNA. of PRDM1 as a postinduction repressor of the IFN␤ promoter Copyright © 2007 by The American Association of Immunologists, Inc. 0022-1767/07/$2.00 during cellular viral infection suggested that PRDM1 is a key www.jimmunol.org The Journal of Immunology 7615 regulator of cellular responses to IFNs (12). The optimum plasmid preparations. The data are from a representative experiment dis- PRDM1 DNA-binding sequence overlaps with the IFN regula- played as fold increase in light units relative to unstimulated cells cotrans- tory factor-element (IRF-E) (27, 28), and we recently showed fected with the empty vector. that PRDM1 has the ability to regulate an IFN-␥-responsive Antibodies promoter by competing with IRFs for occupancy of an IRF-E Rabbit antisera to PRDM1 have been described previously (19, 32). (19). Given these characteristics, PRDM1 is a candidate to act Rabbit polyclonal Abs to IRF-1 and IRF-2 were obtained from Santa as a transcriptional repressor controlling MHC class I-depen- Cruz Biotechnology. Nonimmune rabbit IgG was obtained from Upstate dent Ag-presentation pathways. Biotechnology. Abs used for flow cytometry were mouse IgG2a con- Only a subset of IRF-E sequences, among all IFN-␥-responsive jugated to PE (BD Biosciences) and monoclonal anti-human HLA-ABC gene regulatory elements, are potential targets for PRDM1-depen- conjugated to PE (clone W6/32; DakoCytomation). Mouse mAb to TA- PASIN, clone 16, was obtained from BD Biosciences, goat polyclonal dent repression (19, 28). In this study, we demonstrate that the Ab to human keratin (GTX28572) was obtained from GeneTex, and promoters of multiple linked genes on the MHC class I Ag-pro- mouse mAb to ␤-actin, clone AC15, was obtained from Sigma-Aldrich. cessing and -loading pathway contain conserved IRF-E sequences Secondary Abs for immunofluorescence were Alexa Fluor 488 donkey which allow competitive binding by PRDM1 and IRFs. PRDM1 anti-mouse, Alexa Fluor 594 donkey anti-rabbit, and biotinylated
Load more

Recommended publications
  • Screening and Identification of Key Biomarkers in Clear Cell Renal Cell Carcinoma Based on Bioinformatics Analysis
    bioRxiv preprint doi: https://doi.org/10.1101/2020.12.21.423889; this version posted December 23, 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. Screening and identification of key biomarkers in clear cell renal cell carcinoma based on bioinformatics analysis Basavaraj Vastrad1, Chanabasayya Vastrad*2 , Iranna Kotturshetti 1. Department of Biochemistry, Basaveshwar College of Pharmacy, Gadag, Karnataka 582103, India. 2. Biostatistics and Bioinformatics, Chanabasava Nilaya, Bharthinagar, Dharwad 580001, Karanataka, India. 3. Department of Ayurveda, Rajiv Gandhi Education Society`s Ayurvedic Medical College, Ron, Karnataka 562209, India. * Chanabasayya Vastrad [email protected] Ph: +919480073398 Chanabasava Nilaya, Bharthinagar, Dharwad 580001 , Karanataka, India bioRxiv preprint doi: https://doi.org/10.1101/2020.12.21.423889; this version posted December 23, 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. Abstract Clear cell renal cell carcinoma (ccRCC) is one of the most common types of malignancy of the urinary system. The pathogenesis and effective diagnosis of ccRCC have become popular topics for research in the previous decade. In the current study, an integrated bioinformatics analysis was performed to identify core genes associated in ccRCC. An expression dataset (GSE105261) was downloaded from the Gene Expression Omnibus database, and included 26 ccRCC and 9 normal kideny samples. Assessment of the microarray dataset led to the recognition of differentially expressed genes (DEGs), which was subsequently used for pathway and gene ontology (GO) enrichment analysis.
    [Show full text]
  • Gene Expression Polarization
    Transcriptional Profiling of the Human Monocyte-to-Macrophage Differentiation and Polarization: New Molecules and Patterns of Gene Expression This information is current as of September 27, 2021. Fernando O. Martinez, Siamon Gordon, Massimo Locati and Alberto Mantovani J Immunol 2006; 177:7303-7311; ; doi: 10.4049/jimmunol.177.10.7303 http://www.jimmunol.org/content/177/10/7303 Downloaded from Supplementary http://www.jimmunol.org/content/suppl/2006/11/03/177.10.7303.DC1 Material http://www.jimmunol.org/ References This article cites 61 articles, 22 of which you can access for free at: http://www.jimmunol.org/content/177/10/7303.full#ref-list-1 Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision by guest on September 27, 2021 • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2006 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Transcriptional Profiling of the Human Monocyte-to-Macrophage Differentiation and Polarization: New Molecules and Patterns of Gene Expression1 Fernando O.
    [Show full text]
  • Activated Peripheral-Blood-Derived Mononuclear Cells
    Transcription factor expression in lipopolysaccharide- activated peripheral-blood-derived mononuclear cells Jared C. Roach*†, Kelly D. Smith*‡, Katie L. Strobe*, Stephanie M. Nissen*, Christian D. Haudenschild§, Daixing Zhou§, Thomas J. Vasicek¶, G. A. Heldʈ, Gustavo A. Stolovitzkyʈ, Leroy E. Hood*†, and Alan Aderem* *Institute for Systems Biology, 1441 North 34th Street, Seattle, WA 98103; ‡Department of Pathology, University of Washington, Seattle, WA 98195; §Illumina, 25861 Industrial Boulevard, Hayward, CA 94545; ¶Medtronic, 710 Medtronic Parkway, Minneapolis, MN 55432; and ʈIBM Computational Biology Center, P.O. Box 218, Yorktown Heights, NY 10598 Contributed by Leroy E. Hood, August 21, 2007 (sent for review January 7, 2007) Transcription factors play a key role in integrating and modulating system. In this model system, we activated peripheral-blood-derived biological information. In this study, we comprehensively measured mononuclear cells, which can be loosely termed ‘‘macrophages,’’ the changing abundances of mRNAs over a time course of activation with lipopolysaccharide (LPS). We focused on the precise mea- of human peripheral-blood-derived mononuclear cells (‘‘macro- surement of mRNA concentrations. There is currently no high- phages’’) with lipopolysaccharide. Global and dynamic analysis of throughput technology that can precisely and sensitively measure all transcription factors in response to a physiological stimulus has yet to mRNAs in a system, although such technologies are likely to be be achieved in a human system, and our efforts significantly available in the near future. To demonstrate the potential utility of advanced this goal. We used multiple global high-throughput tech- such technologies, and to motivate their development and encour- nologies for measuring mRNA levels, including massively parallel age their use, we produced data from a combination of two distinct signature sequencing and GeneChip microarrays.
    [Show full text]
  • Angiogenic Patterning by STEEL, an Endothelial-Enriched Long
    Angiogenic patterning by STEEL, an endothelial- enriched long noncoding RNA H. S. Jeffrey Mana,b, Aravin N. Sukumara,b, Gabrielle C. Lamc,d, Paul J. Turgeonb,e, Matthew S. Yanb,f, Kyung Ha Kub,e, Michelle K. Dubinskya,b, J. J. David Hob,f, Jenny Jing Wangb,e, Sunit Dasg,h, Nora Mitchelli, Peter Oettgeni, Michael V. Seftonc,d,j, and Philip A. Marsdena,b,e,f,1 aInstitute of Medical Science, University of Toronto, Toronto, ON M5S 1A8, Canada; bKeenan Research Centre for Biomedical Science in the Li Ka Shing Knowledge Institute, St. Michael’s Hospital, University of Toronto, Toronto, ON M5B 1T8, Canada; cDonnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E2, Canada; dInstitute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON M5S 3G9, Canada; eDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada; fDepartment of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada; gArthur and Sonia Labatt Brain Tumour Research Institute, Hospital for SickKids, University of Toronto, Toronto, ON M5G 1X8, Canada; hDivision of Neurosurgery and Keenan Research Centre for Biomedical Science, St. Michael’s Hospital, University of Toronto, Toronto, ON M5B 1W8, Canada; iDepartment of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115; and jDepartment of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON M5S 3E5, Canada Edited by Napoleone Ferrara, University of California, San Diego, La Jolla, CA, and approved January 24, 2018 (received for review August 28, 2017) Endothelial cell (EC)-enriched protein coding genes, such as endothelial formation in vitro and blood vessel formation in vivo.
    [Show full text]
  • Anti-Inflammatory Role of Curcumin in LPS Treated A549 Cells at Global Proteome Level and on Mycobacterial Infection
    Anti-inflammatory Role of Curcumin in LPS Treated A549 cells at Global Proteome level and on Mycobacterial infection. Suchita Singh1,+, Rakesh Arya2,3,+, Rhishikesh R Bargaje1, Mrinal Kumar Das2,4, Subia Akram2, Hossain Md. Faruquee2,5, Rajendra Kumar Behera3, Ranjan Kumar Nanda2,*, Anurag Agrawal1 1Center of Excellence for Translational Research in Asthma and Lung Disease, CSIR- Institute of Genomics and Integrative Biology, New Delhi, 110025, India. 2Translational Health Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, 110067, India. 3School of Life Sciences, Sambalpur University, Jyoti Vihar, Sambalpur, Orissa, 768019, India. 4Department of Respiratory Sciences, #211, Maurice Shock Building, University of Leicester, LE1 9HN 5Department of Biotechnology and Genetic Engineering, Islamic University, Kushtia- 7003, Bangladesh. +Contributed equally for this work. S-1 70 G1 S 60 G2/M 50 40 30 % of cells 20 10 0 CURI LPSI LPSCUR Figure S1: Effect of curcumin and/or LPS treatment on A549 cell viability A549 cells were treated with curcumin (10 µM) and/or LPS or 1 µg/ml for the indicated times and after fixation were stained with propidium iodide and Annexin V-FITC. The DNA contents were determined by flow cytometry to calculate percentage of cells present in each phase of the cell cycle (G1, S and G2/M) using Flowing analysis software. S-2 Figure S2: Total proteins identified in all the three experiments and their distribution betwee curcumin and/or LPS treated conditions. The proteins showing differential expressions (log2 fold change≥2) in these experiments were presented in the venn diagram and certain number of proteins are common in all three experiments.
    [Show full text]
  • Identification of Transcriptomic Differences Between Lower
    International Journal of Molecular Sciences Article Identification of Transcriptomic Differences between Lower Extremities Arterial Disease, Abdominal Aortic Aneurysm and Chronic Venous Disease in Peripheral Blood Mononuclear Cells Specimens Daniel P. Zalewski 1,*,† , Karol P. Ruszel 2,†, Andrzej St˛epniewski 3, Dariusz Gałkowski 4, Jacek Bogucki 5 , Przemysław Kołodziej 6 , Jolanta Szyma ´nska 7 , Bartosz J. Płachno 8 , Tomasz Zubilewicz 9 , Marcin Feldo 9,‡ , Janusz Kocki 2,‡ and Anna Bogucka-Kocka 1,‡ 1 Chair and Department of Biology and Genetics, Medical University of Lublin, 4a Chod´zkiSt., 20-093 Lublin, Poland; [email protected] 2 Chair of Medical Genetics, Department of Clinical Genetics, Medical University of Lublin, 11 Radziwiłłowska St., 20-080 Lublin, Poland; [email protected] (K.P.R.); [email protected] (J.K.) 3 Ecotech Complex Analytical and Programme Centre for Advanced Environmentally Friendly Technologies, University of Marie Curie-Skłodowska, 39 Gł˛ebokaSt., 20-612 Lublin, Poland; [email protected] 4 Department of Pathology and Laboratory Medicine, Rutgers-Robert Wood Johnson Medical School, One Robert Wood Johnson Place, New Brunswick, NJ 08903-0019, USA; [email protected] 5 Chair and Department of Organic Chemistry, Medical University of Lublin, 4a Chod´zkiSt., Citation: Zalewski, D.P.; Ruszel, K.P.; 20-093 Lublin, Poland; [email protected] St˛epniewski,A.; Gałkowski, D.; 6 Laboratory of Diagnostic Parasitology, Chair and Department of Biology and Genetics, Medical University of Bogucki, J.; Kołodziej, P.; Szyma´nska, Lublin, 4a Chod´zkiSt., 20-093 Lublin, Poland; [email protected] J.; Płachno, B.J.; Zubilewicz, T.; Feldo, 7 Department of Integrated Paediatric Dentistry, Chair of Integrated Dentistry, Medical University of Lublin, M.; et al.
    [Show full text]
  • Supplementary Table S1. Correlation Between the Mutant P53-Interacting Partners and PTTG3P, PTTG1 and PTTG2, Based on Data from Starbase V3.0 Database
    Supplementary Table S1. Correlation between the mutant p53-interacting partners and PTTG3P, PTTG1 and PTTG2, based on data from StarBase v3.0 database. PTTG3P PTTG1 PTTG2 Gene ID Coefficient-R p-value Coefficient-R p-value Coefficient-R p-value NF-YA ENSG00000001167 −0.077 8.59e-2 −0.210 2.09e-6 −0.122 6.23e-3 NF-YB ENSG00000120837 0.176 7.12e-5 0.227 2.82e-7 0.094 3.59e-2 NF-YC ENSG00000066136 0.124 5.45e-3 0.124 5.40e-3 0.051 2.51e-1 Sp1 ENSG00000185591 −0.014 7.50e-1 −0.201 5.82e-6 −0.072 1.07e-1 Ets-1 ENSG00000134954 −0.096 3.14e-2 −0.257 4.83e-9 0.034 4.46e-1 VDR ENSG00000111424 −0.091 4.10e-2 −0.216 1.03e-6 0.014 7.48e-1 SREBP-2 ENSG00000198911 −0.064 1.53e-1 −0.147 9.27e-4 −0.073 1.01e-1 TopBP1 ENSG00000163781 0.067 1.36e-1 0.051 2.57e-1 −0.020 6.57e-1 Pin1 ENSG00000127445 0.250 1.40e-8 0.571 9.56e-45 0.187 2.52e-5 MRE11 ENSG00000020922 0.063 1.56e-1 −0.007 8.81e-1 −0.024 5.93e-1 PML ENSG00000140464 0.072 1.05e-1 0.217 9.36e-7 0.166 1.85e-4 p63 ENSG00000073282 −0.120 7.04e-3 −0.283 1.08e-10 −0.198 7.71e-6 p73 ENSG00000078900 0.104 2.03e-2 0.258 4.67e-9 0.097 3.02e-2 Supplementary Table S2.
    [Show full text]
  • Expression and Regulation of Sex Determining Genes in the Mouse
    Expression and regulation of sex determining genes in the mouse. Veronica Mercedes Narvaez Padilla A thesis submitted for the Degree of Doctor of Philosophy 1996 Department of Developmental Genetics Department of Biology National Institute for Medical Research, University College London The Ridgeway, Mill Hill, Gower Street, London, NW7 lAA London, WCIE GET ProQuest Number: 10016705 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. uest. ProQuest 10016705 Published by ProQuest LLC(2016). Copyright of the Dissertation is held by the Author. All rights reserved. This work is protected against unauthorized copying under Title 17, United States Code. Microform Edition © ProQuest LLC. ProQuest LLC 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106-1346 In memory of Pepe and Arturo. ...Many times Fve been alone and many times Fve cried. Anyway you’ll never know the many ways Fve tried... (Lennon & M cC artney) Little darling, it’s being a long cold lonely winter. Little darling, it feels like years since it’s been here. Here comes the sun, here comes the sun and I say It’s alright! (G. Harrison) Contents Contents ...................................................................................................................................................4
    [Show full text]
  • Prognostic Impact of Concurrent MYC and BCL6 Rearrangements and Expression in De Novo Diffuse Large B-Cell Lymphoma
    www.impactjournals.com/oncotarget/ Oncotarget, Vol. 7, No. 3 Prognostic impact of concurrent MYC and BCL6 rearrangements and expression in de novo diffuse large B-cell lymphoma Qing Ye1,*, Zijun Y. Xu-Monette1,*, Alexandar Tzankov2,*, Lijuan Deng1, Xiaoxiao Wang1, Ganiraju C. Manyam3, Carlo Visco4, Santiago Montes-Moreno5, Li Zhang3, Karen Dybkær6, April Chiu7, Attilio Orazi8, Youli Zu9, Govind Bhagat10, Kristy L. Richards11, Eric D. Hsi12, William W.L. Choi13, J. Han van Krieken14, Jooryung Huh15, Maurilio Ponzoni16, Andrés J.M. Ferreri16, Ben M. Parsons17, Michael B. Møller18, Miguel A. Piris5, Jane N. Winter19, L. Jeffrey Medeiros1 Shimin Hu1 and Ken H. Young1,20 1 Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA 2 University Hospital, Basel, Switzerland 3 Department of Computational Biology and Bioinformatics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA 4 San Bortolo Hospital, Vicenza, Italy 5 Hospital Universitario Marques de Valdecilla, Santander, Spain 6 Aalborg University Hospital, Aalborg, Denmark 7 Memorial Sloan-Kettering Cancer Center, New York, New York, USA 8 Weill Medical College of Cornell University, New York, New York, USA 9 Houston Methodist Hospital, Houston, Texas, USA 10 Columbia University Medical Center and New York Presbyterian Hospital, New York, New York, USA 11 University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA 12 Cleveland Clinic, Cleveland, Ohio, USA 13 University of Hong Kong Li Ka Shing Faculty of Medicine, Hong Kong, China 14 Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands 15 Asan Medical Center, Ulsan University College of Medicine, Seoul, Korea 16 San Raffaele H.
    [Show full text]
  • Genetic Variations of ISL1 Associated with Human Congenital Heart Disease in Chinese Han People
    Genetic variations of ISL1 associated with human congenital heart disease in Chinese Han people Z.L. Luo1, H. Sun2, Z.Q. Yang2, Y.H. Ma3, Y. Gu1, Y.Q. He2, D. Wei4, L.B. Xia4, B.H. Yang1 and T. Guo1 1Department of Cardiology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China 2Department of Medical Genetics, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, Yunnan, China 3Department of Obstetrics and Gynecology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China 4Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China Corresponding author: T. Guo E-mail: [email protected] Genet. Mol. Res. 13 (1): 1329-1338 (2014) Received January 2, 2013 Accepted May 23, 2013 Published February 28, 2014 DOI http://dx.doi.org/10.4238/2014.February.28.5 ABSTRACT. Congenital heart disease (CHD) is the most common birth abnormality, but the etiology of CHD is unknown. ISL1 may play a fundamental role in cardiac morphogenesis, and mutations of this gene could cause CHD. To evaluate whether genetic variations of ISL1 are associated with CHD in Chinese Han people, polymerase chain reaction restriction fragment-length polymorphism and SNaPshot were used to examine 9 polymorphisms of ISL1 in 233 patients with CHD Genetics and Molecular Research 13 (1): 1329-1338 (2014) ©FUNPEC-RP www.funpecrp.com.br Z.L. Luo et al. 1330 as well as 288 healthy controls. We found that one SNP (rs1017) in ISL1 was significantly associated with simple CHD. Genetic variation of ISL1 was confirmed to be associated with the risk of CHD.
    [Show full text]
  • Proteasome Biology: Chemistry and Bioengineering Insights
    polymers Review Proteasome Biology: Chemistry and Bioengineering Insights Lucia Raˇcková * and Erika Csekes Centre of Experimental Medicine, Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Dúbravská cesta 9, 841 04 Bratislava, Slovakia; [email protected] * Correspondence: [email protected] or [email protected] Received: 28 September 2020; Accepted: 23 November 2020; Published: 4 December 2020 Abstract: Proteasomal degradation provides the crucial machinery for maintaining cellular proteostasis. The biological origins of modulation or impairment of the function of proteasomal complexes may include changes in gene expression of their subunits, ubiquitin mutation, or indirect mechanisms arising from the overall impairment of proteostasis. However, changes in the physico-chemical characteristics of the cellular environment might also meaningfully contribute to altered performance. This review summarizes the effects of physicochemical factors in the cell, such as pH, temperature fluctuations, and reactions with the products of oxidative metabolism, on the function of the proteasome. Furthermore, evidence of the direct interaction of proteasomal complexes with protein aggregates is compared against the knowledge obtained from immobilization biotechnologies. In this regard, factors such as the structures of the natural polymeric scaffolds in the cells, their content of reactive groups or the sequestration of metal ions, and processes at the interface, are discussed here with regard to their
    [Show full text]
  • Advancing the Role of Gamma-Tocotrienol As Proteasomes Inhibitor: a Quantitative Proteomic Analysis of MDA-MB-231 Human Breast Cancer Cells
    biomolecules Article Advancing the Role of Gamma-Tocotrienol as Proteasomes Inhibitor: A Quantitative Proteomic Analysis of MDA-MB-231 Human Breast Cancer Cells Premdass Ramdas 1,2, Ammu Kutty Radhakrishnan 3 , Asmahani Azira Abdu Sani 4 , Mangala Kumari 5, Jeya Seela Anandha Rao 6 and Puteri Shafinaz Abdul-Rahman 1,7,* 1 Department of Molecular Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia; [email protected] 2 Department of Medical Biotechnology, School of Health Sciences, International Medical University, 57000 Kuala Lumpur, Malaysia 3 Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway, 47500 Selangor, Malaysia; [email protected] 4 Malaysian Genome Institute, National Institute of Biotechnology, 43000 Bangi, Malaysia; [email protected] 5 Division of Human Biology, International Medical University, 57000 Kuala Lumpur, Malaysia; [email protected] 6 Division of Pathology, International Medical University, 57000 Kuala Lumpur, Malaysia; [email protected] 7 University of Malaya Centre of Proteomics Research (UMCPR), University of Malaya, 50603 Kuala Lumpur, Malaysia * Correspondence: [email protected] Received: 27 November 2019; Accepted: 14 December 2019; Published: 21 December 2019 Abstract: Tocotrienol, an analogue of vitamin E has been known for its numerous health benefits and anti-cancer effects. Of the four isoforms of tocotrienols, gamma-tocotrienol (γT3) has been frequently reported for their superior anti-tumorigenic activity in both in vitro and in vivo studies, when compared to its counterparts. In this study, the effect of γT3 treatment in the cytoplasmic and nuclear fraction of MDA-MB-231 human breast cancer cells were assessed using the label-free quantitative proteomics analysis.
    [Show full text]