Proteasomes: The World of Regulatory Proteolysis
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Edited By:Wolfgang HiltInstitut für Biochemie Universitat Stüttgart
Dieter H. Wolf Published: 2000-10-01 |
This book highlights proteasome structures and how they are related to different aspects of proteasome function. Moreover, the book reports on the functional roles these highly developed proteolytic machines play within the cell. It was a great surprise to the scientific world that proteolysis provides crucial functions in cellular regulation. The surprise was even greater when it was found that not lysosomes, but protease complexes with remarkably sophisticated architectures were responsible for the control of essential regulatory events. Excitingly, proteasomes were found to be involved in widespread functions of cell physiology, which included degradation of protein waste, antigen presentation, regulation of cell metabolism and cell differentiation as well as control of the cell cycle. The discovery of such multiple and essential functions made investigation of proteasome mediated regulatory proteolysis a highly significant theme in cell biology. Written by pioneers in the field the book represents a comprehensive up-to-date view on proteasome structures and functions from the ultimate frontier of cell biology research. It ties the reader to all facets of cell function. This work is an indispensable source for scientists working in the fields of basic and applied cell biology and immunology. Different aspects of proteasome functions are associated with the development of detrimental diseases like cancer, neurodegeneration, cystic fibrosis or immune disorders. Therefore, data reviewed in this book are important for physicians and pharmacologists active in research, and experts in the pharmaceutical industry.
Chapters available from this book
Subunit Arrangement in the Human Proteasome
Burkhardt Dahlmann, Klavs B. Hendil, Poul Kristensen, Wolfgang Uerkvitz, Axel Sobek and Friedrich Kopp
The cytoplasm of mammalian tissues contains high concentrations of 20S proteasomes, the core of the major cytosolic proteolytic system.1 This multicatalytic proteinase degrades proteins into oligopeptides of about 3-15 amino acids.2,3 To protect cellular proteins fr...
Active Sites and Assembly of the 20S Proteasome
Wolfgang Heinemeyer
During the past decade, rapid progress was made in elucidating the 20S proteasomes structure, as well as in establishing its unusual proteolytic mechanism. This was enormously facilitated by the discovery of ancestral proteasome particles in certain bacterial species which led to the fir...
The Regulatory Particle of the Yeast Proteasome
Michael H. Glickman, David M. Rubin, Christopher N. Larsen, Marion Schmidt and Daniel Finley
The ubiquitin-proteasome pathway is a major mediator of posttranslational control in eukaryotes, which functions in the control of cell proliferation, the cell cycle, and other processes. Conjugation of ubiquitin to substrates such as cyclins and p53 target them for degradation by the pr...
Proteasome Crystal Structures
Matthias Bochtler, Lars Ditzel, Daniela Stock, Jan Löwe, Claudia Hartmann, Anja Dorowski, Robert Huber and Michael Groll
Many cellular processes, including stress response, cell cycle control and metabolic adaptation require protein turnover. The diversity of proteins that have to be degraded contrasts with the comparatively small number of proteases that are involved in this process.1 Due to th...
The Mammalian Regulatory Complex of the 26 S Proteasome
Carlos Gorbea and Martin Rechsteiner
It has been nearly two decades since Hershko and colleagues elucidated the
pathway that conjugates ubiquitin (Ub) to intracellular proteins and selects
them for destruction.1-4 A second energy-dependent step in the degradation
of Ub-tagged substrates was identified in 1984.
The 20S Proteasome Activator PA28 or 11S Regulator
Wolfgang Dubiel and Peter Kloetzel
The best characterized endogenous activators of the 20S proteasome are the PA700 or 19S regulator and the PA28 or 11S regulator (11S REG). The 19S regulator forms the 26S proteasome by associating with the 20S proteasome in an ATP-dependent reaction which is described in detail in chapte...
Proteasome Activators and Synthetic Modulators: Significance for Antigen Presentation
Sherwin Wilk, Wei-Er Chen, Cezary Wojcik and Ronald P. Magnusson
Although the 20S proteasome is responsible for the bulk of extralysosomal proteolysis, the purified enzyme has negligible activity toward native proteins and only poorly degrades oligopeptides and unfolded proteins such as casein. This property has been referred to as latency.1
The Proteasome Inhibitors and Their Uses
Do Hee Lee and Alfred L. Goldberg
Knowledge about physiological functions of the proteasome, its biochemical mechanisms, and its importance in cell regulation have developed rather slowly, in large part because of difficulties in measuring rates of protein turnover in vivo and in dissecting the roles of the cell's differ...
Primary Destruction Signals
Erwin Knecht and A. Jennifer Rivett
Proteins that are relatively metabolically stable, with half-lives often exceeding the generation time coexist in the same cell with short-lived proteins that are rapidly degraded. The turnover rates of proteins depend on the physiological state of the cell, and the stability of individu...
The Ubiquitin System in Yeast
Erwin Knecht and A. Jennifer Rivett
For several years, most of the publications in the ubiquitin field began by accentuating the evolutionary conservation of the basic unit of the system, the polypeptide ubiquitin (Ub): ubiquitin is a highly conserved polypeptide of 76 amino acids found in all eukaryotic cells. Of course t...
The Ubiquitin-Proteasome Pathway in Mammals: Mechanisms of Action and Involvement in Pathogenesis of Human Diseases
Aaron Ciechanover, Amir Orian and Alan L. Schwartz
Ubiquitin modification of a variety of cellular proteins plays a major role in numerous basic cellular processes. Among these are regulation of cell cycle and division, differentiation and development, involvement in the cellular response to stress and extracellular modulators, morpho...
Deubiquitinating Enzymes and the Regulation of Proteolysis
Rohan T. Baker
Ubiquitin is a highly conserved eukaryotic protein that is synthesized as a fusion protein precursor, either to itself, or to one of two ribosomal proteins.1 Accordingly, an endopeptidase is required to cleave the fusion precursors to release free ubiquitin. The ubiquitin thus...
Degradation of Ornithine Decarboxylase, a Ubiquitin-Independent Proteasomal Process
Philip Coffino
Posttranslational control of the enzyme ornithine decarboxylase (ODC) employs unusual mechanisms. The proteasome degrades ODC, but ubiquitin is not involved in this process. ODC degradation is instead controlled by the protein antizyme (AZ). This interaction, resulting in the destruction...
The Ubiquitin-Proteasome System in Cell Cycle Control
Carl Mann and Wolfgang Hilt
The duplication and division of cells occurs through a precisely regulated series of morphological and mechanistic steps. This process, termed the cell-division cycle, is controlled by a complex regulatory program. Destruction of regulatory proteins vi...
p53 and the Proteasome Pathway
Martin Scheffner
In agreement with the notion that selective protein degradation is involved in the regulation of many cell regulatory processes, there is increasing evidence that deregulation of degradation can contribute to carcinogenesis. Many proto-oncogene products, for example c-jun,1 ar...
The Role of the Proteasome in Apoptosis
Lisa M. Grimm and Barbara A. Osborne
The regulated death of a cell is important in a variety of biological situations. Cell death is utilized in the selection of immunologically competent T- and B-lymphocytes, in the sculpting or complete removal of tissues during development, and in cytotoxic T lymphocyte (CTL) killing. It...
Function of the Proteasome in the Protein Quality Control Process
Richard K. Plemper and Dieter H. Wolf
Secretion of proteins is an essential mechanism for life. Eukaryotic cells developed the complex central vacuolar system build up by the endoplasmic reticulum (ER), the Golgi apparatus, endosomes, lysosomes, the plasma membrane and intermediate transport compartments to guarantee proper ...
MHC Class I Antigen Presentation and the Proteasome Pathway
Peter-M. Kloetzel and Ulrike Kuckelkorn
As part of the vertebrate immune surveillance system T cells recognize foreign (nonself) antigens which are bound by major histocompatibility complex (MHC) proteins. To allow binding to MHC molecules a protein has to be proteolytically processed to peptides. The recognition of the MHC-pe...
Proteasomes in Prokaryotes
Peter Zwickl, Alfred L. Goldberg and Wolfgang Baumeister
The proteasome was first discovered as a cylinder-shaped particle of unknown function on electron micrographs of human erythrocyte cell lysates.1 More than a decade later, a large multisubunit protease with multicatalytic activity was isolated from bovine pituitary cells,...
The Proteasome in Posttranscriptional Control: A Protease with Endonuclease Activity?
Franck Petit, Claudia Kreutzer-Schmid, Karine Gautier, Anne-Sophie Jarrousse, Saloua Badaoui and Hans-Peter Schmid
Gene expression is regulated at different levels: transcription, translation and posttranslation (Fig. 1).
Cells use different modes of translational control1,2 like phosphorylation of initiation factors, poly (A) tail shortening of the cytoplasmic mess...
Ubiquitin, Proteasomes and Neurodegenerative Disease
Peter-M. Kloetzel and Ulrike Kuckelkorn
While changing money in a bank at Wildbad-Kreut in Bavaria, Germany, in 1990 at a conference on "Proteolysis", one of us (RJM) observed in a pension pamphlet that nearly 40% of the German population would be over the age of 60 by the year 2015. This figure is similar all over t...
Proteasomes: A Historical Retrospective
Dieter H. Wolf
Proteasomes, the world of regulatory proteolysis: surprise and astonishment has struck the scientific community when the structural complexity and principal functions of these large proteinase particles became apparent. From degradation of malfolded proteins, antigen generation, regulato...
