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Glue inside the cell: Ubiquitin builds up an immune response
October 22, 2007Ubiquitin is a small protein, which can be attached to other cellular proteins, a process known as ubiquitination. Discoveries in the 1980 th on a key function of ubiquitination in the regulation of protein degradation where awarded with the Nobel Prize for chemistry in 2004. A study headed by the Junior Group of Dr. Daniel Krappmann (GSF - National Research Center for Environment and Health, Institute of Toxicology) in collaboration with Dr. Jürgen Ruland (TU Munich) and Dr. Claus Scheidereit ( Max-Delbrück-Center , Berlin ) now reports a novel finding about ubiquitination as a key event for the activation of an immune response. (EMBO J. AOP, 18.10.2007).
The acquired immune response is triggered after specific engagement of foreign peptides (antigens) by receptor molecules on white blood cell (lymphocytes). Cellular signaling pathways are responsible for the activation of lymphocytes. Krappmann and co-workers present evidence, that in T cells, which constitute a subgroup of lymphocytes, ubiquitin is attached to the Malt1 protein in response to antigen stimulation. Malt1 is part of the CBM (Carma1-Bcl10-Malt1) complex that constitutes a crucial switch for the activation of the immune defense. Using biochemical, molecular and genetic techniques the scientists could prove that this novel Malt1 ubiquitination is an essential step in the regulation of T cell activation.
'Mechanistically, ubiquitin is virtually acting as all-purpose glue that links different protein components inside the cell', Krappmann explains. 'However, ubiquitination provides an important advantage compared to conventional adhesives: It is reversible, meaning that the associations can be resolved'.
This process of de-ubiquitination is constantly happening in cells and it could contribute to prevent an over-shooting activation of T cells. Unopposed lymphocyte activity is responsible for many chronic diseases, autoimmunity or even lymphoma development. Future work must address the status of Malt1 ubiquitination under pathological conditions, for instance in Malt1 dependent lymphomas. By this the scientists hope to demonstrate the potential of targeting the ubiquitin system for the development of novel therapeutic approaches.
GSF - National Research Center for Environment and Health
This process of de-ubiquitination is constantly happening in cells and it could contribute to prevent an over-shooting activation of T cells. Unopposed lymphocyte activity is responsible for many chronic diseases, autoimmunity or even lymphoma development. Future work must address the status of Malt1 ubiquitination under pathological conditions, for instance in Malt1 dependent lymphomas. By this the scientists hope to demonstrate the potential of targeting the ubiquitin system for the development of novel therapeutic approaches.
GSF - National Research Center for Environment and Health
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Methods in Enzymology, Volume 398: Ubiquitin and Protein Degradation, Part A by Raymond J. Deshaies (Editor) Since the inception of the series, each volume has been eagerly awaited, frequently consulted, and praised by researchers and reviewers alike. The series contains much material still relevant today - truly an essential publication for researchers in all field of life sciences. Ubiquitin and Protein Degradation, Part A will cover high level purification, bioinformatics analysis and substrate identification of the major proteins involved in protein degradation. The chapters are highly methodological and focus primarily on purification and analysis. Topics include: E1 Enzymes E2 Enzymes E3 Enzymes Proteasomes Isopeptidases | |
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Methods in Enzymology, Volume 399: Ubiquitin and Protein Degradation, Part B by Raymond J. Deshaies (Editor) Ubiquitin and Protein Degradation, Part B will cover chemical biology, ubiquitin derivatives and ubiquitin-like proteins, deubiquitinating enzymes, proteomics as well as techniques to monitor protein degradation. The chapters are highly methodological and focus on application of techniques. *Second part of the Ubiquitin and Protein Degration series *Topics include: E1 Enzymes, E2 Enzymes, E3 Enzymes, Proteasomes, and Isopeptidases |
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The Ubiquitin-Proteasome Proteolytic System: From Classical Biochemistry to Human Diseases by Aaron J. Ciechanover (Editor), Maria G. Masucci (Editor) Ubiquitin-proteosome-dependent proteolysis is central to an incredible multitude of processes in all eukaryotes, including the cell cycle, cell growth and differentiation, embryogenesis, apoptosis, signal transduction, DNA repair, regulation of transcription and DNA replication, transmembrane transport, endocytosis, stress responses, antigen presentation and other aspects of the immune response, the functions of the nervous system including circadian rhythms, axon guidance and acquisition of memory. This text tells the story of the ubiquitin system as we know it: from the regulation of basic cellular processes to quality control and the pathogenetic mechanisms of disease, from X-ray crystallography of the 26S proteosome to the interaction between substrates and their ligases, to the... |
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Ubiquitin by M. Rechsteiner (Editor) |
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In vitro-Interaktion der E3-Ubiquitin-Ligase HectH7 mit dem potentiellen Tumorsuppressor CDX2 und Herstellung aufgereinigter polyklonaler Antikörper gegen HectH7 by Sebastian Thaler (Author) | |
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The Ubiquitin Proteasome System in the Central Nervous System: From Physiology to Pathology by Mario Di Napoli (Editor), Cezary Wojcik (Editor) The book focuses on the role of ubiquitin proteasome system (UPS) in central nervous system. Proteasomes are large multicatalytic proteinase complexes that are found in the cytosol and in the nucleus of eukaryotic cells with a central role in cellular protein turnover. The UPS has a central role in the selective degradation of intracellular proteins. In addition to serving as a means to rapidly eliminate short-lived regulatory proteins involved in cell cycle, cell growth, and differentiation, in periods of stress rapid elimination of denatured, misfolded and damaged proteins by the proteasome becomes a critical determinant of cell fate. These aspects are analysed in central nervous system physiology and pathology. |
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Molecular Genetic Analysis of the Ubiquitin-Protein Ligase System of Saccharomyces Cerevisiae by John Patrick McGrath (Author) | |
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