Ubiquitin in signal transduction and cell transformation |
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| Affiliation: | 1. Pediatric Hematology/Oncology and Bone Marrow Transplantation, Hadassah-Hebrew University Medical Center, Jerusalem, Israel;2. Department of Pediatric Oncology, Hematology and Clinical Immunology, University Children’s Hospital, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany;3. Center for Chronic Immunodeficiency, University Medical Center and University of Freiburg, Freiburg, Germany;4. Pediatric Hemato-Oncology Unit, Augusta Victoria Hospital, Jerusalem, Israel;5. Monique and Jacques Roboh Department of Genetic Research, Hadassah, Hebrew University Medical Center, Jerusalem, Israel;1. INSERM UMR 1163, Laboratory of Immunogenetics of Pediatric autoimmune Diseases, 75015 Paris, France;2. Paris Descartes-Sorbonne Paris Cité University, Imagine Institute, 75015 Paris, France;3. Pathology Department, Necker-Enfants Malades University Hospital, Assistance Publique - Hôpitaux de Paris, 75015 Paris, France;4. INSERM UMR 1163, Laboratory of Molecular Mechanisms of Hematologic Disorders and Therapeutic Implications, 75015 Paris, France;5. Paediatric Radiology Department, Necker-Enfants Malades University Hospital, Assistance Publique - Hôpitaux de Paris, 75015 Paris, France;6. Paediatric Immuno-haematology and Rheumatology Department, Necker-Enfants Malades University Hospital, Assistance Publique - Hôpitaux de Paris, 75015 Paris, France;7. Paediatric Department, Jean-Verdier Hospital, Assistance Publique - Hôpitaux de Paris, 93140 Bondy, France;8. Genomic Platform, INSERM UMR 1163, Paris Descartes Sorbonne Paris Cité University, Imagine Institute, 75015 Paris, France;9. INSERM UMR 1163, Bioinformatics Department, Institute Imagine, 75015 Paris, France;10. INSERM UMR 1163, Imagine Institute, 75015 Paris, France |
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| Abstract: | Since the discovery of ubiquitin-dependent protein degradation almost two decades ago, great strides have been made towards a detailed understanding of the biochemistry of this process (reviewed in [1–3]). It was, however, only in recent years that the physiological role of the ubiquitin system in signal transduction and the regulation of several cell functions started to be appreciated and experimentally addressed. As with other principal mechanisms of signal transduction, such as phosphorylation or GTP hydrolysis, much of the information regarding the role of the ubiquitin system as a component of cell regulation and signaling cascades, was gained in studies of transformation and the control of cell growth. It seems, however, that ubiquitin-dependent proteolysis, and possibly other processes that are controlled by protein ubiquitination, play a role in many aspects of cellular function from the control of differentiation to intracellular trafficking [1,3,4]. Here we will review some of the results that implicate ubiquitin-dependent proteolysis in the control of cell growth and that indicate how perturbations of ubiquitin-dependent degradation of oncogene and tumor suppressor gene products may contribute to cell transformation and oncogenesis. |
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