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Conjugation and Deconjugation of Ubiquitin Family Modifiers
† 1 a a 4 † 17 10 15 ubiquitin; and of 16 VCP 17 18 20 33 34 34 36 p domain. 41 42 42 43 P U 42 47 binding. C. elegans 16 In 21 22 50 51 52 53 13 and UFD 4 10 of Cdc48. 18 30 of Ufd2. COFACTORS 47 23 13 47 47 47 72 15 15 and of Spt23 p90. Ufd2 and Cdc48. In C. elegans 74 16 75 75 76 76 Ufd2 25 54 54 7 56 p47 7 7 80 30 30 81 82 82 but and CD3 26 DUB COFACTORS 30 UFD3 OTU1 4 Cdc48 30 4 OLE1. 15 27 87 REFERENCES 30 REGULATION OF UBIQUITIN MONOUBIQUITINATION UBIQUITINATION 1 32 7 S) d 33 12 13 14 15 18 19 15 20 21 35 15 15 27 15 31 32 31 33 36 monoubiquitination of pol pol 34 37 34 monoubiquitination. 20 35 trans 3 15 REFERENCES by monoubiquitination. Mol Cell; 2009. UBIQUITIN LIGASE ACTIVITY BY Nedd 1 2 of 41 5 6 8 fold. 9 13 14 edd 43 18 18 K M and k 18 22 23 K M 24 25 K M 26 edd 45 18 27 K M K D 18 25 . 8 10 M 21 28 MECHANISM AND REGULATION OF CRLs 34 41 34 edd 47 48 S. pombe 49 51 p27 and I by SCF and SCF 57 58 59 60 CTD CTD CTD CTD in Cul5 CTD CTD CTD 60 18
Proteasome Inhibitors in Cancer Therapy
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.
Adoptive Immunotherapy
An authoritative collection of optimal techniques for producing and characterizing the immunologically active cells and effector molecules now gaining wide use in the clinical treatment of patients. Taking advantage of the latest technologies, the authors present readily reproducible experimental protocols for the study of dendritic cells, T cells, monoclonal antibodies, and bone marrow transplantation. The emphasis is on preclinicical and clinical applications and on the progress of selected approaches in clinical trials. Additional chapters cover the molecular definition of target antigens, mathematical modeling approaches to immunotherapy, and the utilization of regulatory T cells. The protocols make it possible to study the adoptive transfer of tailored antigen-specific immune cells and to improve the clinical application of adoptive immunotherapy.
Ubiquitin and Ubiquitin-like Protein Modifiers
Ubiquitination and Protein Stability - Part A Volume 618, the latest release in the Methods in Enzymology series, highlights new advances in the field, with this updated volume presenting interesting chapter written by an international board of authors. Topics of note in this new release include the Preparation of ubiquitinated nucleosomes with native and non-hydrolyzable linkages, Methods to measure ubiquitin chain length and linkage, Genetic approaches to study the yeast ubiquitin system, Enzymatic preparation of monoubiquitinated proteins, Methods to distinguish the function of ubiquitin in autophagy and the proteasome pathway, the Purification and characterization of enzyme activity of USPs, and much more. - Provides the authority and expertise of leading contributors from an international board of authors - Presents the latest release in this series on enzymology - Updated release includes the latest information on methods to measure ubiquitin chain length and linkage, genetic approaches to study the yeast ubiquitin system, amongst many other timely topics
Modelling Proteasome Dynamics in a Bayesian Framework
Sabine Stübler compares different proteasome isoforms and subtypes in terms of their transport and active site-related parameters applying an existing computational model. In a second step, the author extends this model to be able to describe the influence of proteasome inhibitors in in vitro experiments. The computational model, which describes the hydrolysis of short fluorogenic peptides by the 20S proteasome, is calibrated to experimental data from different proteasome isoforms using an approximate Bayesian computation approach. The dynamics of proteasome inhibitors are included into the model in order to demonstrate how to modulate the inhibitor’s transport parameters for strong or isoform-specific inhibition.
Structural and Functional Characterization of the Immunoproteasome
In this acclaimed thesis, Eva Maria Huber reveals ground-breaking results by elucidating the crystal structure of the murine immunoproteasome in complex with a selective inhibitor. Huber does this by performing multidisciplinary methodologies including X-ray crystallography, fluorescence spectroscopy and mutagenesis experiments. Her exceptional results explore the immunoproteasome complex structures and are of outstanding importance for future scientific research especially in the pharmaceutical industry. These results will enable the functional analysis of individual proteasome subunits and support the development of novel drugs for autoimmune diseases such as multiple sclerosis or rheumatoid arthritis.
Carbonic Anhydrase: Mechanism, Regulation, Links to Disease, and Industrial Applications
The study of carbonic anhydrase has spanned multiple generations of scientists. Carbonic anhydrase was first discovered in 1932 by Meldrum and Roughton. Inhibition by sulfanilamide was shown in 1940 by Mann and Keilin. Even Hans Krebs contributed to early studies with a paper in 1948 showing the relationship of 25 different sulfonamides to CA inhibition. It was he who pointed out the importance of both the charged and uncharged character of these compounds for physiological experiments. The field of study that focuses on carbonic anhydrase (CA) has exploded in recent years with the identification of new families and isoforms. The CAs are metalloenzymes which are comprised of 5 structurally d...
Harnessing the Participation of Dendritic Cells in Immunity and Tolerance
This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact.
Reprogramming Microbial Metabolic Pathways
Metabolic engineering has been developed over the past 20 years to become an important tool for rational engineering of microorganisms. This book has a particular interest in the methods and applications of metabolic engineering to improve the production and yield of a variety of metabolites in microorganisms. The overall goal is to achieve a better understanding of metabolism in different microorganisms, and provide a rational basis to reprogram microorganisms for improved biochemical production. This book brings together contributions from leading researchers at the cutting edge of these topics. The subject matter is divided into two sections. The first section deals with novel and emerging methods for redesigning microorganisms exploiting systems biology and gene regulation. The second discusses practical aspects of metabolic engineering for over production of a variety of valuable chemicals and materials by fermentation.
Epigenetics: Development and Disease
Epigenetics fine-tunes the life processes dictated by DNA sequences, but also kick-starts pathophysiological processes including diabetes, AIDS and cancer. This volume tracks the latest research on epigenetics, including work on new-generation therapeutics.
