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Author: Arnab De Publisher: Springer ISBN: 3319149652 Category : Science Languages : en Pages : 119
Book Description
This thesis examines the evidence for regulatory ubiquitination by focusing on A20. It provides an insightful and in-depth evaluation of the current literature by critically examining the evidence of K63-linked regulatory ubiquitination in regulating cell-signalling. It is also the first thesis to directly test the role of regulatory ubiquitination in NF-kB signaling in vivo. The case for regulatory ubiquitination has been to a large extent predicated upon the presumed deubiquitinase activity of A20, long considered a key regulator of inflammatory responses as mice lacking A20 die from multi-organ inflammation and cachexia. The theses reports the creation and characterization of a knock-in mouse that expresses a mutated form of A20 which selectively lacks the deubiquitinase activity. The knock-in mice surprisingly display completely normal NF-κB activation with no accompanying inflammatory phenotype. Given that the presumed role of A20 as a deubiquitinase has been used to support the importance of regulatory K63-linked ubiquitination in NF-kB signaling, this study will help focus future research efforts into alternative target pathways that do not depend on K63 ubiquitination. In fact, the work suggests that it might be important to revisit the role of K63-linked polyubiquitination in cell-signalling. Ubiquitin Chains: Degradation and Beyond is essential reading for anyone conducting research in cell-signalling and immunology. Dr. Arnab De received his PhD from the Department of Microbiology & Immunology at Columbia University. During his PhD, he developed transgenic mice to study the mechanism of action of a critical tumor-suppressor called A20. He is also well known for having developed peptide-based prodrugs as therapeutics for diabetes. His work has been reported by the media, and has resulted in multiple patents and publications in peer reviewed journals. He presented his findings at the American Peptide Symposium and was awarded the Young Investigator’s Award. He is the author of the book entitled Application of Peptide-Based Prodrug Chemistry in Drug Development, with a foreword written by Professor Jean Martinez (Former President, European Peptide Society) and published in the series SpringerBriefs in Pharmaceutical Science & Drug Development. His research interests lie at the intersection of chemistry and medicine. Besides biomedical research, he is also generally interested in public health policy and general scientific outreach.
Author: Arnab De Publisher: Springer ISBN: 3319149652 Category : Science Languages : en Pages : 119
Book Description
This thesis examines the evidence for regulatory ubiquitination by focusing on A20. It provides an insightful and in-depth evaluation of the current literature by critically examining the evidence of K63-linked regulatory ubiquitination in regulating cell-signalling. It is also the first thesis to directly test the role of regulatory ubiquitination in NF-kB signaling in vivo. The case for regulatory ubiquitination has been to a large extent predicated upon the presumed deubiquitinase activity of A20, long considered a key regulator of inflammatory responses as mice lacking A20 die from multi-organ inflammation and cachexia. The theses reports the creation and characterization of a knock-in mouse that expresses a mutated form of A20 which selectively lacks the deubiquitinase activity. The knock-in mice surprisingly display completely normal NF-κB activation with no accompanying inflammatory phenotype. Given that the presumed role of A20 as a deubiquitinase has been used to support the importance of regulatory K63-linked ubiquitination in NF-kB signaling, this study will help focus future research efforts into alternative target pathways that do not depend on K63 ubiquitination. In fact, the work suggests that it might be important to revisit the role of K63-linked polyubiquitination in cell-signalling. Ubiquitin Chains: Degradation and Beyond is essential reading for anyone conducting research in cell-signalling and immunology. Dr. Arnab De received his PhD from the Department of Microbiology & Immunology at Columbia University. During his PhD, he developed transgenic mice to study the mechanism of action of a critical tumor-suppressor called A20. He is also well known for having developed peptide-based prodrugs as therapeutics for diabetes. His work has been reported by the media, and has resulted in multiple patents and publications in peer reviewed journals. He presented his findings at the American Peptide Symposium and was awarded the Young Investigator’s Award. He is the author of the book entitled Application of Peptide-Based Prodrug Chemistry in Drug Development, with a foreword written by Professor Jean Martinez (Former President, European Peptide Society) and published in the series SpringerBriefs in Pharmaceutical Science & Drug Development. His research interests lie at the intersection of chemistry and medicine. Besides biomedical research, he is also generally interested in public health policy and general scientific outreach.
Author: Peter Zwickl Publisher: Springer Science & Business Media ISBN: 364259414X Category : Science Languages : en Pages : 222
Book Description
This volume gives an overview of pro tea some-mediated protein degradation and the regulatory role of the ubiquitin system in cellular proteolysis. The first chapter describes the molecular evolution of the proteasome and its associated activators, i. e. , the 20S core, the base and the lid of the 19S cap, and the 11 S regulator. The ensuing chapter gives an overview of the structure and assembly of the 20S proteasome and the regulation of the archaeal proteasome by PAN. The third contribution summarizes our knowledge on the eukaryotic 26S proteasome and its regulation by the 19S regu lator, followed by a chapter devoted to the llS regulator, which elucidates the structural basis for the 11 S-mediated activation of the 20S proteasome. The fifth chapter reviews in detail the role of the proteasome in the immune response. The subsequent chapter of the natural substrates of the gives a comprehensive description proteasome and their recognition by the enzymes of the ubiqui tination machinery. The penultimate chapter rounds up the in formation on intracellular distribution of proteasomes in yeast and mammalian cells, while the last contribution highlights proteasome inhibitors, tools which proved to be very valuable for dissecting the cellular roles of the proteasome and which might turn out to be of pharmacological importance.
Author: Matthew Summers Publisher: BoD – Books on Demand ISBN: 1838804900 Category : Science Languages : en Pages : 228
Book Description
The human ubiquitin proteasome system (UPS) is comprised of nearly 1000 proteins. Although originally identified as a mechanism of protein destruction, the UPS has numerous additional functions and mediates central signaling events in myriad processes involved in both cellular and organismal health and homeostasis. Numerous pathways within the UPS are implicated in disease, ranging from cancer to neurodegenerative diseases such as Parkinson's. The goal of this book is to deliver a collection of synopses of current areas of UPS research that highlights the importance of understanding the biology of the UPS to identify disease-relevant pathways, and the need to elucidate the molecular machinations within the UPS to develop methods for therapeutic modulation of these pathways.
Author: Julian Adams Publisher: Springer Science & Business Media ISBN: 1592597947 Category : Medical Languages : en Pages : 319
Book Description
A panel of leading academic and pharmaceutical investigators takes stock of the remarkable work that has been accomplished to date with proteasome inhibitors in cancer, and examines emerging therapeutic possibilities. The topics range from a discussion of the chemistry and cell biology of the proteasome and the rationale for proteasome inhibitors in cancer to a review of current clinical trials underway. The discussion of rationales for testing proteasome inhibitors in cancer models covers the role of the proteasome in NF-kB activation, the combining of conventional chemotherapy and radiation with proteasome inhibition, notably PS-341, new proteasome methods of inhibiting viral maturation, and the role of protesome inhibition in the treatment of AIDS. The authors also document the development of bortezomib (VelcadeTM) in Phase I clinical trials and in a multicentered Phase II clinical trials in patients with relapsed and refractory myeloma.
Author: J. Robin Harris Publisher: Springer Nature ISBN: 3030589714 Category : Science Languages : en Pages : 580
Book Description
This book covers important topics such as the dynamic structure and function of the 26S proteasome, the DNA replication machine: structure and dynamic function and the structural organization and protein–protein interactions in the human adenovirus capsid, to mention but a few. The 18 chapters included here, written by experts in their specific field, are at the forefront of scientific knowledge. The impressive integration of structural data from X-ray crystallography with that from cryo-electron microscopy is apparent throughout the book. In addition, functional aspects are also given a high priority. Chapter 1 is available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.
Author: Jan-Michael Peters Publisher: Springer Science & Business Media ISBN: 0306456494 Category : Science Languages : en Pages : 498
Book Description
The last several years have been a landmark period in the ubiquitin field. The breadth of ubiquitin's roles in cell biology was first sketched, and the importance of ubiquitin-dependent proteolysis as a regulatory mechanism gained general acceptance. The many strands of work that led to this new perception are re counted in this book. A consequence of this progress is that the field has grown dramatically since the first book on ubiquitin was published almost a decade ago [M. Rechsteiner (ed. ), Ubiquitin, Plenum Press, 1988]. In this span, students of the cell cycle, transcription, signal transduction, protein sorting, neuropathology, cancer, virology, and immunology have attempted to chart the role of ubi quit in in their particular experimental systems, and this integration of the field into cell biology as a whole continues at a remarkable pace. We hope that for active researchers in the field as well as for newcomers and those on the fence, this book will prove helpful for its breadth, historical perspective, and practical tips. Structural data are now available on many of the components of the ubiquitin pathway. The structures have provided basic insights into the unusual biochemical mechanisms of ubiquitination and proteasome-mediated proteolysis. Because high-speed computer graphics can convey structures more effectively than print media, we have supplemented the figures of the book with a Worldwide Web site that can display the structures in a flexible, viewer-controlled format.
Author: Sangdun Choi Publisher: Springer ISBN: 9781441904607 Category : Medical Languages : en Pages : 0
Book Description
Biological processes are driven by complex systems of functionally interacting signaling molecules. Thus, understanding signaling molecules is essential to explain normal or pathological biological phenomena. A large body of clinical and experimental data has been accumulated over these years, albeit in fragmented state. Hence, systems biological approaches concomitant with the understanding of each molecule are ideal to delineate signaling networks/pathways involved in the biologically important processes. The control of these signaling pathways will enrich our healthier life. Currently, there are more than 30,000 genes in human genome. However, not all the proteins encoded by these genes work equally in order to maintain homeostasis. Understanding the important signaling molecules as completely as possible will significantly improve our research-based teaching and scientific capabilities. This encyclopedia presents 350 biologically important signaling molecules and the content is built on the core concepts of their functions along with early findings written by some of the world’s foremost experts. The molecules are described by recognized leaders in each molecule. The interactions of these single molecules in signal transduction networks will also be explored. This encyclopedia marks a new era in overview of current cellular signaling molecules for the specialist and the interested non-specialist alike During past years, there were multiple databases to gather this information briefly and very partially. Amidst the excitement of these findings, one of the great scientific tasks of the coming century is to bring all the useful information into a place. Such an approach is arduous but at the end will infuse the lacunas and considerably be a streamline in the understanding of vibrant signaling networks. Based on this easy-approach, we can build up more complicated biological systems.
Author: Thibault Mayor Publisher: Humana ISBN: 9781493993710 Category : Science Languages : en Pages : 413
Book Description
“This volume explores numerous techniques used to study the ubiquitin proteasome system. The chapters in this book are organized into five parts and cover topics such as determining the mechanisms of action for E2s, E3s, and DUB enzymes; the latest advances to study the formation of poly-ubiquitin chains as well as their linkage types; the binding partners of proteins in the UPS; methods for structure determination by x-ray crystallography, cryo electron microscopy and SAXS; screening assays to select for degrons or modulators of E3s and DUBs; proteomics approaches in the ubiquitin field and methods to study 26S proteasome function. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Thorough and authoritative, The Ubiquitin Proteasome System: Methods and Protocols is a valuable resource for both experienced and novice scientists who are interested in expanding their knowledge in this field.
Author: Arnab De
Author: Arnab De
Author: Milton J. Schlesinger
Author: Peter Zwickl
Author: Matthew Summers
Author: Julian Adams
Author: J. Robin Harris
Author: Jan-Michael Peters
Author: Sangdun Choi
Author: Arnab De
Author: Thibault Mayor