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.

The third of four volumes discusses the role of ubiquitin-mediated protein breakdown in cellular regulation and physiology. Required reading for molecular biologists, cell biologists and physiologists with an interest in the topic.

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.

The ubiquitin-proteasome pathway consists of ubiquitin, substrate proteins, E1 enzymes, E2 enzymes, E3 enzymes, and proteasome, which acts in a series of enzymatic reaction chains to ubiquitinate substrate proteins such as surplus and misfolded proteins for degradation by the proteasome to maintain the balance between protein synthesis and degradation in a cell and tissue. Moreover, deubiquitinating enzymes can remove the attached ubiquitin chain, which results in a reverse ubiquitination-deubiquitination process involved in multiple biological processes in a cell and tissue. The changes of components in the ubiquitin-proteasome pathway are associated with multiple pathophysiological processes, such as cancers and neurodegenerative diseases. This book presents the new advances in concepts, analytical methodology, and application of ubiquitin-proteasome pathway for clarification of molecular mechanisms and discovery of new therapeutic targets and drugs in different diseases.

Annotation. The second volume in a new series dedicated to protein degradation, this book discusses the mechanism and cellular functions of targeted protein breakdown via the ubiquitin pathway. Drawing on the combined knowledge of the world's leading protein degradation experts, this handy reference compiles information on the proteasome-mediated degradation steps of the ubiquitin pathway. In addition to proteasomal function and regulation, it also presents the latest results on novel members of the ubiquitin superfamily and their role in cellular regulation. Further volumes in the series cover the function of ubiquitin-protein ligases, and the roles of the ubiquitin pathway in regulating key cellular processes, as well as its pathophysiological disease states. Required reading for molecular biologists, cell biologists and physiologists with an interest in protein degradation.