Search

Your search keyword '"MESH : Neoplasm Proteins"' showing total 7 results
Start Over Descriptor "MESH : Neoplasm Proteins" Topic biology
7 results on '"MESH : Neoplasm Proteins"'

1. Sex differences in the GSK3β-mediated survival of adherent leukemic progenitors

Author

Jessica Bertrand, Bernard Payrastre, N Gallay, Nathalie Vergnolle, Véronique Maguer-Satta, Mathieu Despeaux, Cécile Demur, Ezzeddine Bourogaa, S Joly, P Bonnevialle, F Louache, Claire Racaud-Sultan, ANDRA, Laboratoire d'Hématologie [Purpan], Université Paul Sabatier - Toulouse 3 ( UPS ) -CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Equipe 11, Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de Physiopathologie Toulouse Purpan, Université Paul Sabatier - Toulouse 3 ( UPS ) -IFR30-IFR150-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Departement /u563 : Oncogenèse, Signalisation et Innovation thérapeutique, Université Paul Sabatier - Toulouse 3 ( UPS ) -Institut Claudius Regaud-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Claudius Regaud

Subjects
Male, MESH : Aged, Antigens, CD34, MESH : Blotting, Western, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Glycogen Synthase Kinase 3, 0302 clinical medicine, MESH : Indoles, MESH : Tumor Cells, Cultured, GSK-3, Tumor Cells, Cultured, Protein Phosphatase 2, MESH : GTP-Binding Proteins, Cells, Cultured, MESH: Glycogen Synthase Kinase 3, MESH: Etoposide, Etoposide, MESH: Indoles, MESH : Maleimides, Aged, 80 and over, MESH : Cell Survival, 0303 health sciences, education.field_of_study, MESH: Middle Aged, MESH: Protein Phosphatase 2, Neoplasm Proteins, MESH: Cell Survival, MESH: Young Adult, 030220 oncology & carcinogenesis, Neoplastic Stem Cells, RNA Interference, MESH: Cells, Cultured, MESH : Protein Phosphatase 2, MESH : Glycogen Synthase Kinase 3, MESH: Antineoplastic Agents, Phytogenic, Blotting, Western, MESH : Young Adult, Receptors, Cell Surface, MESH: Cell Adhesion, 03 medical and health sciences, MESH : Neoplasm Proteins, MESH: Sex Factors, Genetics, MESH: Blotting, Western, Humans, MESH : Middle Aged, MESH: Tumor Cells, Cultured, Progenitor cell, MESH : Aged, 80 and over, Clonogenic assay, education, Molecular Biology, Aged, MESH: Interleukin-3 Receptor alpha Subunit, MESH: Humans, Glycogen Synthase Kinase 3 beta, MESH : Hematopoietic Stem Cells, MESH : Humans, MESH : Leukemia, MESH: Adult, MESH: Antigens, CD34, Protein phosphatase 2, Hematopoietic Stem Cells, MESH: Neoplastic Stem Cells, Immunology, MESH: Female, MESH: Neoplasm Proteins, Cancer Research, Indoles, MESH : Receptors, Cell Surface, MESH : Interleukin-3 Receptor alpha Subunit, MESH : Antineoplastic Agents, Phytogenic, MESH: Hematopoietic Stem Cells, Maleimides, MESH: Aged, 80 and over, MESH : Female, MESH: Maleimides, MESH: Receptors, Cell Surface, MESH: Aged, Leukemia, Myeloid leukemia, MESH : Adult, Middle Aged, medicine.anatomical_structure, MESH : Antigens, CD34, Female, Stem cell, Adult, MESH: GTP-Binding Proteins, Cell Survival, MESH : Male, MESH : Sex Factors, MESH: RNA Interference, Population, Interleukin-3 Receptor alpha Subunit, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH : Etoposide, Biology, Receptors for Activated C Kinase, Young Adult, MESH : Neoplastic Stem Cells, Sex Factors, GTP-Binding Proteins, MESH: Leukemia, MESH : Cells, Cultured, Cell Adhesion, medicine, 030304 developmental biology, Antineoplastic Agents, Phytogenic, MESH: Male, MESH : Cell Adhesion, Cancer research, Bone marrow, MESH : RNA Interference
Abstract

International audience; Therapeutic resistance of acute myeloid leukemia stem cells, enriched in the CD34(+)38(-)123(+) progenitor population, is supported by extrinsic factors such as the bone marrow niche. Here, we report that when adherent onto fibronectin or osteoblast components, CD34(+)38(-)123(+) progenitors survive through an integrin-dependent activation of glycogen synthase kinase 3β (GSK3β) by serine 9-dephosphorylation. Strikingly, GSK3β-mediated survival was restricted to leukemic progenitors from female patients. GSK3β inhibition restored sensitivity to etoposide, and impaired the clonogenic capacities of adherent leukemic progenitors from female patients. In leukemic progenitors from female but not male patients, the scaffolding protein RACK1, activated downstream of α(5)β(1)-integrin engagement, was specifically upregulated and controlled GSK3β activation through the phosphatase protein phosphatase 2A (PP2A). In a mirrored manner, survival of adherent progenitors (CD34(+)38(-)) from male but not female healthy donors was partially dependent on this pathway. We conclude that the GSK3β-dependent survival pathway might be sex-specific in normal immature population and flip-flopped upon leukemogenesis. Taken together, our results strengthen GSK3β as a promising target for leukemic stem cell therapy and reveal gender differences as a new parameter in anti-leukemia therapy.

Published
2011
Full Text
View/download PDF

2. A protocol to quantify mammary early common progenitors from long-term mammosphere culture

Author

Véronique Maguer-Satta, Emmanuel Delay, Elodie Bachelard-Cascales, Marion Chapellier, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Claude Bernard Lyon 1 ( UCBL ), and Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS )

Subjects
MESH: Neoplasm Proteins, Time Factors, Cellular differentiation, Cell Culture Techniques, MESH : Aged, MESH : Receptors, Cell Surface, MESH : Blotting, Western, MESH : Interleukin-3 Receptor alpha Subunit, MESH : Antineoplastic Agents, Phytogenic, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH: Hematopoietic Stem Cells, Mice, 0302 clinical medicine, MESH: Aged, 80 and over, MESH : Indoles, MESH : Tumor Cells, Cultured, MESH : Female, MESH : GTP-Binding Proteins, MESH: Glycogen Synthase Kinase 3, MESH: Maleimides, MESH: Receptors, Cell Surface, MESH: Etoposide, MESH : Maleimides, MESH: Aged, MESH: Indoles, MESH : Cell Survival, 0303 health sciences, MESH: Middle Aged, Stem Cells, MESH: Protein Phosphatase 2, Cell Differentiation, General Medicine, MESH : Adult, Cell biology, MESH: Cell Survival, MESH: Young Adult, 030220 oncology & carcinogenesis, MESH : Antigens, CD34, Stem cell, MESH: Cells, Cultured, Adult, MESH: GTP-Binding Proteins, MESH : Protein Phosphatase 2, MESH : Glycogen Synthase Kinase 3, MESH : Male, MESH : Sex Factors, MESH: RNA Interference, MESH: Antineoplastic Agents, Phytogenic, MESH : Young Adult, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH : Etoposide, Biology, MESH: Cell Adhesion, Colony-Forming Units Assay, 03 medical and health sciences, MESH : Neoplasm Proteins, MESH : Neoplastic Stem Cells, MESH: Sex Factors, Spheroids, Cellular, MESH : Cells, Cultured, MESH: Leukemia, Animals, Humans, MESH: Blotting, Western, MESH : Middle Aged, MESH: Tumor Cells, Cultured, Progenitor cell, Mammary Glands, Human, MESH : Aged, 80 and over, 030304 developmental biology, Progenitor, MESH: Interleukin-3 Receptor alpha Subunit, MESH: Humans, MESH : Hematopoietic Stem Cells, Stem cell population, MESH : Humans, MESH : Leukemia, MESH: Adult, Cell Biology, MESH: Antigens, CD34, MESH: Neoplastic Stem Cells, MESH: Male, MESH : Cell Adhesion, Cell culture, Immunology, NIH 3T3 Cells, MESH : RNA Interference, MESH: Female, Developmental Biology
Abstract

International audience; Here we describe a protocol established in our laboratory to quantify early common progenitors/stem cells grown as spheres in non-adherent culture conditions. This protocol is based on the combination of two functional tests: the mammosphere assay to maintain and enrich early mammary progenitors/stem cells, and the epithelial colony-forming cells (E-CFC) assay to identify and quantify further differentiated epithelial progenitors. Primary spheres mainly contain progenitors and rare stem/early common progenitor cells while secondary and tertiary spheres contain progenitor cells derived from the early common progenitor/stem cell population maintained through passages and partially differentiated. Spheres are enzymatically and mechanically dissociated; the derived cells are subsequently plated on irradiated NIH-3T3 fibroblasts for further processing, as in the E-CFC assay. The principle of this assay is to quantify the number of epithelial colonies generated by cells present in the different sequential spheres. This assay has therefore been named ECP-DC, standing for Early Common Progenitor-Derived Colonies assay.

Published
2012
Full Text
View/download PDF

3. Aberrant DNA methylation of cancer-associated genes in gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST)

Author

Karen Balassiano, Jean-Yves Scoazec, Pierre Hainaut, Petra H.M. Peeters, Federico Canzian, Göran Hallmans, Sara Grioni, Domenico Palli, Bakary S. Sylla, Karina Meidtner, Marí a.José Sánchez, Carmen Navarro, Antonia Trichopoulou, J. Ramón Quirós, Ruth C. Travis, Kim Overvad, Roy Ehrnström, Eva Ardanaz, Eiliv Lund, Carlos A. González, Salvatore Panico, Pagona Laglou, H. Bas Bueno-de-Mesquita, G. Johan A. Offerhaus, Zdenko Herceg, Sheila Coelho Soares Lima, Mazda Jenab, Naomi E. Allen, Kay-Tee Khaw, Rudolf Kaaks, Sara Regnér, Anne Tjønneland, Roger Stenling, Françoise Clavel-Chapelon, Elio Riboli, Heiner Boeing, Núria Sala, M. E. Numans, Marie-Christine Boutron-Ruault, Miren Dorronsoro, Rosario Tumino, Paolo Vineis, Unit of Nutrition, Environment, and Cancer, Catalan Institute of Oncology, Department of Cardiology, Aalborg Hospital-Aarhus University Hospital, Danish Cancer Society, Institute of Cancer Epidemiology, Centre de recherche en épidémiologie et santé des populations ( CESP ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Nutrition, hormones et cancer: épidémiologie et prévention ( E3N ), Epidémiologie, sciences sociales, santé publique ( IFR 69 ), Université Panthéon-Sorbonne ( UP1 ) -Université Paris-Sud - Paris 11 ( UP11 ) -École des hautes études en sciences sociales ( EHESS ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Panthéon-Sorbonne ( UP1 ) -Université Paris-Sud - Paris 11 ( UP11 ) -École des hautes études en sciences sociales ( EHESS ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Paris-Sud - Paris 11 ( UP11 ) -Institut Gustave Roussy ( IGR ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Department of Cancer Epidemiology, German Cancer Research Center, Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), German Institute of Human Nutrition Potsdam-Rehbrücke, Department of Epidemiology, German Institute of Human Nutrition, Department of Hygiene, Epidemiology and Medical Statistics, Centre for Environment and Health, Imperial College London-School of public health, Human Genetics Foundation ( HuGeF ), Università degli studi di Torino ( UNITO ), Department of Clinical and Experimental Medicine, Università degli studi di Napoli Federico II-Medical School, Molecular and Nutritional Epidemiology Unit, ISPO-Cancer Research and Prevention Institute, Epidemiology, Cancer Registry, Azienda Ospedaliera 'Civile M.P.Arezzo', Institute of Community Medicine, University of Tromsø ( UiT ), National Institute for Public Health and the Environment [Bilthoven] ( RIVM ), Julius Centre for Health Sciences and Primary Care, University Medical Center, Julius Center for Health Sciences and Primary Care, Consorcio de Investigación Biomédica en Red especializado en Epidemiología y Salud Pública ( CIBERESP ), Los Centros de Investigación Biomédica en Red (CIBER), Granada Cancer Registry, Andalusian School of Public Health, CIBERESP, CIBER Epidemiologia y Salud Pública, Epidemiology Department, Murcia Health Council, Navarra Public Health Institute, Leyre 15, Epidemiology and Health Information, Public Health Department of Gipuzkoa, Department of Public Health and Clinical Medicine/Nutritional Research, University of Umeå, Cancer Epidemiology Unit, University of Oxford [Oxford]-Cancer Epidemiology Unit, School of Clinical Medicine, University of Cambridge [UK] ( CAM ), Department of Epidemiology and Public Health, Imperial College London, International Agency for Cancer Research ( IACR ), International Agency for Cancer Research, Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), General practice, EMGO - Mental health, Aarhus University Hospital, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition, hormones et cancer: épidémiologie et prévention (E3N), Epidémiologie, sciences sociales, santé publique (IFR 69), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), The University of Hong Kong (HKU)-The University of Hong Kong (HKU), Human Genetics Foundation (HuGeF), Università degli studi di Torino = University of Turin (UNITO), Civile - M.P.Arezzo Hospital, University of Tromsø (UiT), National Institute for Public Health and the Environment [Bilthoven] (RIVM), VU University Medical Center [Amsterdam], Consorcio de Investigación Biomédica en Red especializado en Epidemiología y Salud Pública (CIBERESP), Andalusian School of Public Health [Granada], Umeå University, University of Cambridge [UK] (CAM), International Agency for Cancer Research (IACR), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), and Università degli studi di Torino (UNITO)

Subjects
MESH: Neoplasm Proteins, Male, Cancer Research, MESH : Aged, MESH : Prospective Studies, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH: DNA Methylation, 0302 clinical medicine, MESH : Stomach Neoplasms, MESH : Female, Prospective Studies, MESH: Aged, Genetics, 0303 health sciences, Molecular Epidemiology, MESH: Middle Aged, MESH: Genetic Predisposition to Disease, MESH: Stomach Neoplasms, Methylation, Middle Aged, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Neoplasm Proteins, Europe, Oncology, 030220 oncology & carcinogenesis, DNA methylation, Female, MESH : Male, MESH : Europe, MESH : Molecular Epidemiology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, MLH1, 03 medical and health sciences, MESH : Neoplasm Proteins, p14arf, Stomach Neoplasms, medicine, MESH: Molecular Epidemiology, Humans, Genetic Predisposition to Disease, MESH : Middle Aged, Epigenetics, Gene, 030304 developmental biology, Aged, MESH: Humans, MESH : Humans, Cancer, DNA Methylation, medicine.disease, MESH: Prospective Studies, MESH: Male, MESH : Genetic Predisposition to Disease, MESH: Europe, MESH: Female, MESH : DNA Methylation
Abstract

Epigenetic events have emerged as key mechanisms in the regulation of critical biological processes and in the development of a wide variety of human malignancies, including gastric cancer (GC), however precise gene targets of aberrant DNA methylation in GC remain largely unknown. Here, we have combined pyrosequencing-based quantitative analysis of DNA methylation in 98 GC cases and 64 controls nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort and in cancer tissue and non-tumorigenic adjacent tissue of an independent series of GC samples. A panel of 10 cancer-associated genes (CHRNA3, DOK1, MGMT, RASSF1A, p14ARF, CDH1, MLH1, ALDH2, GNMT and MTHFR) and LINE-1 repetitive elements were included in the analysis and their association with clinicopathological characteristics (sex, age at diagnosis, anatomical sub-site, histological sub-type) was examined. Three out of the 10 genes analyzed exhibited a marked hypermethylation, whereas two genes (ALDH2 and MTHFR) showed significant hypomethylation, in gastric tumors. Among differentially methylated genes, we identified new genes (CHRNA3 and DOK1) as targets of aberrant hypermethylation in GC, suggesting that epigenetic deregulation of these genes and their corresponding cellular pathways may promote the development and progression of GC. We also found that global demethylation of tumor cell genomes occurs in GC, consistent with the notion that abnormal hypermethylation of specific genes occurs concomitantly with genome-wide hypomethylation. Age and gender had no significant influence on methylation states, but an association was observed between LINE-1 and MLH1 methylation levels with histological sub-type and anatomical sub-site. This study identifies aberrant methylation patters in specific genes in GC thus providing information that could be exploited as novel biomarkers in clinics and molecular epidemiology of GC. © 2011 Elsevier Ireland Ltd.

Published
2011
Full Text
View/download PDF

4. Analysis of the DND1 gene in men with sporadic and familial testicular germ cell tumors

Author

Gedske Daugaard, Sophie D. Fosså, Sergei Tjulandin, Walter P. Weber, Douglas F. Easton, Rachel Linger, Dominique Stoppa-Lyonnet, Peter Albers, David W. Hogg, Parry Guilford, Robert Huddart, Michael Friedlander, Peter A. Daly, Ketil Heimdal, Michael A.S. Jewett, Darshna Dudakia, Michael R. Stratton, Katherine L. Nathanson, Hans Stoll, Lajos Géczi, Mary L. McMaster, Catherine Bonaïti-Pellié, Stéphane Richard, Elizabeth A. Rapley, Lawrence H. Einhorn, Mark H. Greene, Victoria K. Cortessis, Edith Olah, Agnès Chompret, Axel Heidenreich, Radka Lohynska, Katherine M. Tucker, Kelly-Anne Phillips, D. Timothy Bishop, Larissa A. Korde, Ludmila Liubchenko, István Bodrogi, Section of Cancer Genetics, Institute of cancer research, Academic Radiotherapy Unit, Dept of Medical Oncology, Division of Medicine, University of New South Wales [Sydney] (UNSW)-Prince of Wales Hospital Randwick, Dept of Haematology and Medical Oncology, Peter MacCallum Cancer Center, Princess Margaret Hospital, University of Toronto, Dept of Radiotherapy and Oncology, University hospital of Prague, Dept of Oncology, Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Génétique oncologique (GO - UMR 8125), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Service d'urologie, Hôpital Bicêtre-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), Centre de Recherches Biologiques, CERB, Génomes et cancer (GC (FRE2939)), Département de Pédiatrie, Institut Gustave Roussy (IGR), Epidémiologie des cancers, Institut National de la Santé et de la Recherche Médicale (INSERM), Onco-génétique, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Service de Génétique Oncologique, Institut Curie [Paris], Département de génétique, Unité de génétique et biologie des cancers (U830), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Génétique épidémiologique et structures des populations humaines (Inserm U535), Epidémiologie, sciences sociales, santé publique (IFR 69), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Epidémiologie génétique, Dept of Urological Oncology, Phillips university, Department of Urology, Klinikum Kassel GmbH, Department of Molecular Genetics and Department of Chemotherapy, National Institute of Oncology, Department of Medical Oncology, St James's hospital, Cancer Genetics Laboratory, University of Otago [Dunedin, Nouvelle-Zélande], Departments of Clinical Cancer Research and genetics, Rikshospitalet-Radiumhospitalet Trust, Laboratory of Clinical Genetics, Institute of Clinical Oncology, Medical Oncology, University Hospital Basel [Basel], Google Inc., Institut de Physique et Chimie des Matériaux de Strasbourg (IPCMS), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Barts and The London Queen Mary's School of Medicine, Clinical Genetics Branch, Division of Cancer Epidemiology & Genetics, National Institutes of Health [Bethesda] (NIH)-National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Depts of Medicine and Biostatistics and Epidemology, Abramson Family Cancer Research Institute-Perelman School of Medicine, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia], Department of Preventive Medicine, Keck School of Medicine [Los Angeles], University of Southern California (USC)-University of Southern California (USC), Cancer Research U.K. Genetic Epidemiology Unit, Strangeways Research Laboratory, Genetic Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge [UK] (CAM), Genetic Epidemiology Division, Cancer Research UK Clinical Centre, Saint James's University Hospital, University of New South Wales [Sydney] ( UNSW ) -Prince of Wales Hospital Randwick, Peter MacCallum Cancer Centre, University of Toronto-Princess Margaret Hospital, Génétique oncologique ( GO - UMR 8125 ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut Gustave Roussy ( IGR ) -Centre National de la Recherche Scientifique ( CNRS ), Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, Génomes et cancer ( GC (FRE2939) ), Institut Gustave Roussy ( IGR ), Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut Gustave Roussy ( IGR ) -Institut Gustave Roussy ( IGR ), INSTITUT CURIE, Unité de génétique et biologie des cancers ( U830 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Génétique épidémiologique et structures des populations humaines ( Inserm U535 ), Epidémiologie, sciences sociales, santé publique ( IFR 69 ), Université Panthéon-Sorbonne ( UP1 ) -Université Paris-Sud - Paris 11 ( UP11 ) -École des hautes études en sciences sociales ( EHESS ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Panthéon-Sorbonne ( UP1 ) -Université Paris-Sud - Paris 11 ( UP11 ) -École des hautes études en sciences sociales ( EHESS ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), University of Otago, Institut de Physique et Chimie des Matériaux de Strasbourg ( IPCMS ), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique ( CNRS ), National Institutes of Health ( NIH ) -National Cancer Institute ( NIH ), Abramson Family Cancer Research Institute-University of Pennsylvania School of Medicine, University of Cambridge [UK] ( CAM ), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Institut Curie, Université Paris Descartes - Paris 5 (UPD5)-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, MESH: Neoplasm Proteins, Cancer Research, DNA Mutational Analysis, medicine.disease_cause, Polymerase Chain Reaction, law.invention, 0302 clinical medicine, law, Polymorphism (computer science), Family history, MESH: DNA Mutational Analysis, MESH : Polymerase Chain Reaction, Polymerase chain reaction, MESH: Testicular Neoplasms, Genetics, 0303 health sciences, Mutation, MESH: Genetic Predisposition to Disease, Neoplasms, Germ Cell and Embryonal, Neoplasm Proteins, medicine.anatomical_structure, 030220 oncology & carcinogenesis, MESH: Neoplasms, Germ Cell and Embryonal, MESH : Mutation, Germ cell, [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], MESH: Mutation, MESH : Male, MESH : DNA Mutational Analysis, Biology, MESH : Family Health, Article, 03 medical and health sciences, MESH : Neoplasm Proteins, MESH : Neoplasms, Germ Cell and Embryonal, Testicular Neoplasms, medicine, Genetic predisposition, Humans, Genetic Predisposition to Disease, MESH : Testicular Neoplasms, [ SDV.OT ] Life Sciences [q-bio]/Other [q-bio.OT], Gene, 030304 developmental biology, Family Health, MESH: Humans, MESH : Humans, Cancer, MESH: Polymerase Chain Reaction, medicine.disease, MESH: Male, MESH: Family Health, MESH : Genetic Predisposition to Disease
Abstract

A base substitution in the mouse Dnd1 gene resulting in a truncated Dnd protein has been shown to be responsible for germ cell loss and the development of testicular germ cell tumors (TGCT) in the 129 strain of mice. We investigated the human orthologue of this gene in 263 patients (165 with a family history of TGCT and 98 without) and found a rare heterozygous variant, p. Glu86Ala, in a single case. This variant was not present in control chromosomes (0/4,132). Analysis of the variant in an additional 842 index TGCT cases (269 with a family history of TGCT and 573 without) did not reveal any additional instances. The variant, p. Glu86Ala, is within a known functional domain of DND1 and is highly conserved through evolution. Although the variant may be a rare polymorphism, a change at such a highly conserved residue is characteristic of a disease-causing variant. Whether it is disease-causing or not, mutations in DND1 make, at most, a very small contribution to TGCT susceptibility in adults and adolescents.

Published
2008
Full Text
View/download PDF

5. Spectrum of NPHP6/CEP290 mutations in Leber congenital amaurosis and delineation of the associated phenotype

Author

Josseline Kaplan, Jean-Louis Dufier, Hélène Dollfus, Elisa Fazzi, Arnold Munnich, Nathalie Delphin, Sylvie Gerber, Olivier Roche, Jean-Michel Rozet, Sylvain Hanein, Isabelle Perrault, Sabine Defoort-Dhellemmes, Virology Laboratory, Hôpital Rothchild, Neurologie et thérapeutique expérimentale, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -IFR70-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Department of cell biology, Harvard Medical School [Boston] ( HMS ), Taplin Biological Mass Spectrometry Facility, Biogéosciences [Dijon] ( BGS ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), Centre de recherche thérapeutique en ophtalmologie, Université Paris Descartes - Paris 5 ( UPD5 ) -EA2502, EA no 2502 du ministère de la Recherche, de l'Enseignement Supérieur et la Technologie, Université Paris Descartes - Paris 5 ( UPD5 ) -CERTO, Service d'ophtalmologie [CHU Necker], CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP), Laboratoire Magmas et Volcans ( LMV ), Université Blaise Pascal - Clermont-Ferrand 2 ( UBP ) -Institut national des sciences de l'Univers ( INSU - CNRS ) -Université Jean Monnet [Saint-Étienne] ( UJM ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Neurosciences Fonctionnelles et Pathologies ( LNFP ), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique ( CNRS ), Institut de génétique et biologie moléculaire et cellulaire ( IGBMC ), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Service de génétique médicale, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], IFR Necker-Enfants Malades ( IRNEM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement ( Inserm U781 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), CHU Necker - Enfants Malades [AP-HP], Handicaps génétiques de l'enfant ( Inserm U393 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Groupe de Physique des Solides ( GPS ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Institut des Nanosciences de Paris ( INSP ), Centre National de la Recherche Scientifique ( CNRS ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR70-Université Pierre et Marie Curie - Paris 6 (UPMC), Harvard Medical School [Boston] (HMS), Biogéosciences [UMR 6282] [Dijon] (BGS), Centre National de la Recherche Scientifique (CNRS)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Université Paris Descartes - Paris 5 (UPD5)-EA2502, Université Paris Descartes - Paris 5 (UPD5)-CERTO, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de Neurosciences Fonctionnelles et Pathologies (LNFP), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), IFR Necker-Enfants Malades (IRNEM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement (Inserm U781), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Handicaps génétiques de l'enfant (Inserm U393), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Groupe de Physique des Solides (GPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut des Nanosciences de Paris (INSP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), CHU Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR70-Institut National de la Santé et de la Recherche Médicale (INSERM), Biogéosciences [UMR 6282] (BGS), Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR70-Université Pierre et Marie Curie - Paris 6 ( UPMC ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS ), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
MESH: Neoplasm Proteins, Retinal degeneration, Linkage disequilibrium, genetic structures, MESH: Introns, MESH: Antigens, Neoplasm, Cell Cycle Proteins, MESH : Child, Preschool, Linkage Disequilibrium, MESH : Antigens, Neoplasm, MESH : Frameshift Mutation, Exon, 0302 clinical medicine, MESH : Exons, MESH : Child, MESH: Child, Genotype, Child, Frameshift Mutation, Genetics (clinical), Genetics, 0303 health sciences, MESH : Linkage Disequilibrium, MESH : Optic Atrophy, Hereditary, Leber, MESH: Frameshift Mutation, MESH : Infant, Exons, MESH : Adult, MESH: Infant, Phenotype, Neoplasm Proteins, 3. Good health, MESH: Linkage Disequilibrium, Child, Preschool, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Adult, Optic Atrophy, Hereditary, Leber, Biology, MESH : Introns, Frameshift mutation, 03 medical and health sciences, MESH : Neoplasm Proteins, Antigens, Neoplasm, Intronic Mutation, medicine, Humans, Allele, Alleles, 030304 developmental biology, MESH: Humans, MESH: Alleles, MESH: Child, Preschool, MESH : Humans, Infant, MESH: Optic Atrophy, Hereditary, Leber, MESH: Adult, medicine.disease, Introns, eye diseases, Cytoskeletal Proteins, [ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], 030221 ophthalmology & optometry, sense organs, MESH: Exons, MESH : Alleles
Abstract

International audience; Leber congenital amaurosis (LCA) is the earliest and most severe retinal degeneration responsible for congenital blindness. Hitherto, 13 LCA genes have been mapped, nine of which have been identified. Recently, mutations in the NPHP6/CEP290 gene were shown to account for Joubert and Senior-Loken syndromes and to represent a frequent cause of isolated LCA. All LCA patients shared an intronic mutation resulting in an aberrantly spliced transcript and low levels of wild-type transcript that was believed to explain the absence of cerebellar and renal involvement in these patients. Here, we confirm the high frequency of NPHP6/CEP290 mutations in our series of LCA families hailing worldwide (22%). However, we show that conversely to other LCA genes, NPHP6 is involved in families of European descent only (38/38). A total of 24 different mutations were found, 23 of which are novel (one founder mutation in the North region of France). All mutations but two were either nonsense, frameshift, or splice-site changes. The common NPHP6/CEP290 intronic mutation accounted for 43% (33/76) of all disease alleles. Twelve families did not carry this common intronic mutation. At least 10 out of them harboured two mutations expected to truncate the protein questioning the relevance of the assumption according to which the retinal-restricted phenotype in LCA patient could be due to a residual NPHP6/CEP290 activity. Finally, we show that all patients were affected with the cone-rod subtype of the disease whatever their NPHP6/CEP290 genotype.

Published
2007
Full Text
View/download PDF

6. STD and TRNOESY NMR studies for the epitope mapping of the phosphorylation motif of the oncogenic protein beta-catenin recognized by a selective monoclonal antibody

Author

Simon Megy, Gildas Bertho, Richard Benarous, Françoise Baleux, Josyane Gharbi-Benarous, Jean-Pierre Girault, Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Chimie Organique, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques ( LCBPT - UMR 8601 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Centre National de la Recherche Scientifique ( CNRS ), Chimie Organique ( UCO ), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Institut Cochin ( UMR_S567 / UMR 8104 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Chimie Organique (UCO), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)

Subjects
Models, Molecular, MESH: Neoplasm Proteins, Magnetic Resonance Spectroscopy, Amino Acid Motifs, MESH: beta Catenin, Peptide, Nuclear Overhauser effect, 01 natural sciences, Biochemistry, Epitope, MESH: Antibodies, Monoclonal, MESH : Phosphorylation, Epitopes, MESH: Amino Acid Motifs, MESH: Protein Structure, Tertiary, Structural Biology, Neoplasms, MESH: Nuclear Magnetic Resonance, Biomolecular, TRNOESY, MESH: Neoplasms, Phosphorylation, beta Catenin, MESH : Ubiquitin, chemistry.chemical_classification, 0303 health sciences, biology, Chemistry, MESH : Peptides, MESH: Peptides, Antibodies, Monoclonal, Nuclear magnetic resonance spectroscopy, P-β-Catenin/antibody complex, Ubiquitin ligase, Neoplasm Proteins, Restrained molecular dynamics, MESH : Antibodies, Monoclonal, MESH : SKP Cullin F-Box Protein Ligases, Two-dimensional nuclear magnetic resonance spectroscopy, MESH : Protein Structure, Tertiary, Binding fragment, MESH: Models, Molecular, MESH: SKP Cullin F-Box Protein Ligases, MESH : Amino Acid Motifs, MESH: Ubiquitin, MESH: Epitopes, MESH : Models, Molecular, Biophysics, MESH : Epitopes, MESH : Nuclear Magnetic Resonance, Biomolecular, Bound structure, 010402 general chemistry, 03 medical and health sciences, MESH : Neoplasm Proteins, P-β-Catenin phosphorylated peptide, Genetics, Humans, Molecular Biology, Nuclear Magnetic Resonance, Biomolecular, Antibody, 030304 developmental biology, MESH : Protein Processing, Post-Translational, MESH: Epitope Mapping, SKP Cullin F-Box Protein Ligases, MESH: Humans, MESH: Phosphorylation, Ubiquitin, MESH: Magnetic Resonance Spectroscopy, β-Catenin oncogenic protein, MESH : Humans, Cell Biology, MESH : beta Catenin, MESH : Neoplasms, 0104 chemical sciences, Protein Structure, Tertiary, STD NMR, Epitope mapping, MESH : Epitope Mapping, MESH: Protein Processing, Post-Translational, biology.protein, MESH : Magnetic Resonance Spectroscopy, Peptides, Protein Processing, Post-Translational, Epitope Mapping, Conformational epitope
Abstract

International audience; The interaction of the P-beta-Cat(19-44) peptide, a 26 amino acid peptide (K(19)AAVSHWQQQSYLDpSGIHpSGATTTAP(44)) that mimics the phosphorylated beta-Catenin antigen, has been studied with its monoclonal antibody BC-22, by transferred nuclear Overhauser effect NMR spectroscopy (TRNOESY) and saturation transfer difference NMR (STD NMR) spectroscopy. This antibody is specific to diphosphorylated beta-Catenin and does not react with the non-phosphorylated protein. Phosphorylation of beta-Catenin at sites Ser33 and Ser37 on the DSGXXS motif is required for the interaction of beta-Catenin with the ubiquitin ligase SCF(beta-TrCP). beta-TrCP is involved in the ubiquitination and proteasome targeting of the oncogenic protein beta-Catenin, the accumulation of which has been implicated in various human cancers. The three-dimensional structure of the P-beta-Cat(19-44) in the bound conformation was determined by TRNOESY NMR experiments; the peptide adopts a compact structure in the presence of mAb with formation of turns around Trp25 and Gln26, with a tight bend created by the DpS(33)GIHpS(37) motif; the peptide residues (D32-pS37) forming this bend are recognized by the antibody as demonstrated by STD NMR experiments. STD NMR studies provide evidence for the existence of a conformational epitope containing tandem repeats of phosphoserine motifs. The peptide's epitope is predominantly located in the large bend and in the N-terminal segment, implicating bidentate association. These findings are in excellent agreement with a recently published NMR structure required for the interaction of beta-Catenin with the SCF(beta-TrCP) protein.

Published
2006
Full Text
View/download PDF

7. Cellular FLICE-inhibitory protein: an attractive therapeutic target?

Author

Olivier Micheau, Mort cellulaire et cancer, Université de Bourgogne ( UB ) -IFR100 - Structure fédérative de recherche Santé-STIC-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Bourgogne (UB)-IFR100 - Structure fédérative de recherche Santé-STIC-Institut National de la Santé et de la Recherche Médicale (INSERM), and Micheau, Olivier

Subjects
MESH: Neoplasm Proteins, MESH: Signal Transduction, MESH: CASP8 and FADD-Like Apoptosis Regulating Protein, MESH : Drug Design, MESH: Mice, Inbred NOD, apoptosis and human diseases, MESH : Multiple Sclerosis, Clinical Biochemistry, CASP8 and FADD-Like Apoptosis Regulating Protein, Arthritis, MESH : Alzheimer Disease, Apoptosis, MESH : Alternative Splicing, Disease, MESH : Models, Biological, MESH: Drug Design, Arthritis, Rheumatoid, MESH : Diabetes Mellitus, Type 1, Mice, 0302 clinical medicine, MESH: Lymphoproliferative Disorders, Mice, Inbred NOD, Neoplasms, MESH: Autoimmune Diseases, Drug Discovery, MESH: Neoplasms, MESH: Animals, MESH : Cardiovascular Diseases, 0303 health sciences, MESH: Arthritis, Rheumatoid, MESH : Gene Expression Regulation, MESH : Lymphoproliferative Disorders, MESH: Alternative Splicing, Intracellular Signaling Peptides and Proteins, MESH: Gene Expression Regulation, 3. Good health, Neoplasm Proteins, medicine.anatomical_structure, Cardiovascular Diseases, 030220 oncology & carcinogenesis, Molecular Medicine, Signal transduction, Alzheimer's disease, MESH: Diabetes Mellitus, Type 1, Signal Transduction, Multiple Sclerosis, c-FLIP, T cell, Biology, Inhibitor of apoptosis, Models, Biological, Article, Autoimmune Diseases, 03 medical and health sciences, MESH : Neoplasm Proteins, MESH : Autoimmune Diseases, MESH : Intracellular Signaling Peptides and Proteins, Alzheimer Disease, MESH: Intracellular Signaling Peptides and Proteins, MESH : Mice, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Mice, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, Pharmacology, MESH : Signal Transduction, MESH: Humans, MESH : Mice, Inbred NOD, MESH: Apoptosis, MESH : Humans, MESH: Models, Biological, MESH: Cardiovascular Diseases, MESH: Multiple Sclerosis, MESH : CASP8 and FADD-Like Apoptosis Regulating Protein, medicine.disease, MESH : Neoplasms, Lymphoproliferative Disorders, Alternative Splicing, Diabetes Mellitus, Type 1, Gene Expression Regulation, Flip, Drug Design, Immunology, MESH : Arthritis, Rheumatoid, MESH : Animals, MESH: Alzheimer Disease, MESH : Apoptosis
Abstract

International audience; Cellular FLIP (c-FLIP), also known as FLICE-inhibitory protein, has been identified as an inhibitor of apoptosis triggered by engagement of death receptors (DRs) such as Fas or TRAIL (TNF-related apoptosis-inducing ligand). cFLIP is recruited to DR signalling complexes, where it prevents caspase activation. Animal models have indicated that c-FLIP plays an important role in T cell proliferation and heart development. Abnormal c-FLIP expression has been identified in various diseases such as multiple sclerosis (MS), Alzheimer's disease (AD), diabetes mellitus, rheumatoid arthritis (RA) and various cancers. This review focuses on recent insights into c-FLIP dysregulation associated with human diseases and addresses the possibilities of using c-FLIP as a therapeutic target.

Published
2003
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results