Over the last decade, major advancements in our understanding of the ubiquitin-proteasome system (UPS) have occurred. This book focuses on recent trends in the UPS. The UPS is possibly the most complex of all intracellular pathways as close to 7% of all genes in the human genome make up part of the UPS. This complex system serves as an essential role in intracellular protein degradation, and because of its critical function, improper functioning of the UPS is associated with nearly all know diseases, including cancer, cardiovascular disease, and neurological diseases. The proteolytic component of the UPS is the proteasome, a multicatalytic complex found in the nucleus and cytoplasm. Another form of the proteasome, the immunoproteasome, is less abundant than the constitutive proteasome, but is important in immune response and degradation of oxidized proteins, and recent research suggests that it may be important in longevity. The articles in this book discuss recent findings which indicate that mutations in proteins involved with the UPS are associated with genetic diseases such as familial dilated cardiomyopathy, Nakajo syndrome, and spinal muscular atrophy (X-linked). Some chapters also discuss recent results which suggest that the UPS is heavily regulated by post-translational modifications such as phosphorylation, acetylation, and methylation. The UPS is also heavily regulated by ubiquitination itself. This book contains a research article using PubMed bibliometric data to present current research trends in the UPS. Articles are written so that no one tissue is emphasized to allow readers from any discipline to benefit from this information.

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 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.

This book series consists of 3 volumes covering the basic science (Volume 1), clinical science (Volume 2) and the technology and methodology (Volume 3) of autophagy. Volume 1 focuses on the biology of autophagy, including the signaling pathways, regulating processes and biological functions. Autophagy is a fundamental physiological process in eukaryotic cells. It not only regulates normal cellular homeostasis, and organ development and function, but also plays an important role in the pathogenesis of a wide range of human diseases. Thanks to the rapid development of molecular biology and omic technologies, research on autophagy has boomed in recent decades, and more and more cellular and animal models and state-of the-art technologies are being used to shed light on the complexity of signaling networks involved in the autophagic process. Further, its involvement in biological functions and the pathogenesis of various diseases has attracted increased attention around the globe. Presenting cutting-edge knowledge, this book series is a useful reference resource for researchers and clinicians who are working on or interested in autophagy.

“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.

This book, written by members of the European network PROTEOSTASIS, provides an up-to-date review of the research regarding protein homeostasis in health and disease. With new discoveries contributing to the increasing complexity of this topic, the book offers a detailed overview of the pathways regulating protein homeostasis, including autophagy and the ubiquitin protein family. Following a basic introduction, it explains how defects in protein homeostasis contribute to numerous pathologies, including cancer, neurodegeneration, inflammation and a number of rare diseases. In addition, it discusses, the role of protein homeostasis in cellular development and physiology. Highlighting the latest research in the field of protein homeostasis and its implications for various clinically relevant diseases, the book appeals to researchers and clinicians, while also offering a reference guide for scholars who are new to the field.