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This SpringerBrief explores the physiological roles of Skp1-Cullin1-F-box Complex (SCF) and Anaphase Promoting Complex (APC) in normal cells and in tumor formation. These two related, multi-subunit E3 ubiquitin ligase enzymes, APC and SCF are thought to be the major driving forces governing proper cell cycle progression. Defective cell cycle regulation leads to genomic instability and ultimately, cancer development. Selective degradation of key cell cycle regulators by the ubiquitin-proteasome system has been proven to be a major regulatory mechanism for ensuring ordered and coordinated cell cycle progression. The SCF and APC E3 ligases have been characterized to play pivotal roles in regulating the cell cycle progression by timely degrading various critical cell cycle regulators. This Brief reviews recent studies that have shown that deregulation of signaling pathways in which the two ubiquitin ligases are involved causes aberrant cell cycle regulation, in turn leading to tumorigenesis. The text also discusses how SCF and APC may present promising therapeutic targets to treat various cancers.
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.
This book follows on from Volume 83 in the SCBI series (“Macromolecular Protein Complexes”), and addresses several important topics (such as the Proteasome, Anaphase Promoting Complex, Ribosome and Apoptosome) that were not previously included, together with a number of additional exciting topics in this rapidly expanding field of study. Although the first SCBI Protein Complex book focused on soluble protein complexes, the second (Vol. 87)addressed Membrane Complexes, and the third (Vol. 88) put the spotlight on Viral Protein and Nucleoprotein Complexes, a number of membrane, virus and even fibrillar protein complexes have been be considered for inclusion in the present book. A further book is also under preparation that follows the same pattern, in an attempt to provide a thorough coverage of the subject. Chapter 9 is available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.
This book aims to bring together a broad variety of examples of the role of pharmacogenomics in current drug development, uncovering dynamic concentration-dependent drug responses on biological systems to understand pharmacodynamics responses in human cancer where genetic lesions serve as tumor markers and provide a basis for cancer diagnosis. The book describes methods and protocols applied in molecular diagnostics. It offers pathologists and researchers providing molecular diagnostic services an array of the most recent and readily accessible reference to compare methods and techniques. Highlights include the molecular diagnosis of genetic aberrations by quantitative polymerase reaction (qPCR), sequence-specific oligonucleotide arrays, next-generation sequencing (NGS), CGH arrays-and methodologies directed at the detection of epigenetic events, high-throughput nucleic acid and protein arrays, direct sequencing and FISH-based methodologies, currently used in the diagnosis of solid tumors. The book also includes an innovative line of treatment in relation to the molecular prognosis, diagnosis and pharmacogenomics in the actual practice of clinical findings at molecular levels. The book covers the applications of numerous genetic testing methodologies; in approximately the chronological order of discovery and high-throughput diagnosis using advanced genomic approaches to identify such genes, in the search for novel drug targets and/or key determinants of drug reactions. It also promotes a wider understanding of molecular diagnostics among physicians, medical students, and scientists in academics, industry and corporate world.
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.
An overview of the current systems biology-based knowledge and the experimental approaches for deciphering the biological basis of cancer.
This fully revised second edition provides the only unified synthesis of available information concerning the mechanisms of higher-order memory formation. It spans the range from learning theory, to human and animal behavioral learning models, to cellular physiology and biochemistry. It is unique in its incorporation of chapters on memory disorders, tying in these clinically important syndromes with the basic science of synaptic plasticity and memory mechanisms. It also covers cutting-edge approaches such as the use of genetically engineered animals in studies of memory and memory diseases. Written in an engaging and easily readable style and extensively illustrated with many new, full-color figures to help explain key concepts, this book demystifies the complexities of memory and deepens the reader's understanding. - More than 25% new content, particularly expanding the scope to include new findings in translational research. - Unique in its depth of coverage of molecular and cellular mechanisms - Extensive cross-referencing to Comprehensive Learning and Memory - Discusses clinically relevant memory disorders in the context of modern molecular research and includes numerous practical examples
“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 volume brings together a unique collection of protocols that cover standard, novel, and specialized techniques. Cell Cycle Oscillators: Methods and Protocols guides readers through recent progress in the field from both holistic and reductionist perspectives, providing the latest developments in molecular biology techniques, biochemistry, and computational analysis used for studying oscillatory networks. 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. Authoritative and cutting-edge, Cell Cycle Oscillators: Methods and Protocols will serve as an invaluable reference to gain further insight into the complex and incompletely understood processes that are involved in the cell cycle and its regulation by oscillatory networks.
This comprehensive text provides a much-needed review of a disease that is currently garnering the interest of molecular biologists, translational scientists, and clinicians. The volume includes emerging developments in the molecular genetics of endometrial carcinoma. In addition to covering the basic genetics of endometrial carcinoma, chapters also cover a wide range of signaling pathways implicated in endometrial carcinoma. A section of the book includes a number of genetically engineered mouse models, which contribute to understanding the role of various genetic alterations in the development and progression of endometrial carcinoma. These models also provide preclinical models for developing effective targeted therapeutic approaches. Endometrial carcinoma is the most common malignancy of the female genital tract in the United States and the number of cases continues to increase around the world. This book is a meant to serve as a resource for a wide range of scientists, from molecular geneticists to signal transduction biologists, as well as to both clinicians and scientists interested in developing targeted therapeutic approaches for women with endometrial carcinoma.