Download or read book Ubiquitin mediated Degradation Via UPS and Lysosome written by Qizhi Sun and published by . This book was released on 2014 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Ubiquitination plays a fundamental role in determining protein fate. Once ubiquitinated, the cargo is directed to the proteasome for partial or complete degradation or lysosome for complete degradation. Failing to eliminate these cargos results in the accumulation of toxic proteins that contribute to neurodegenerative and immunological diseases, cancer and other human maladies. Thus, identifying proteins subject to ubiquitin-mediated degradation and characterizing the mechanisms governing these processes underscores their importance to human health. The calcium/calmodulin-dependent serine protein kinase (CASK) is one such protein that is required for brain development. However, mutations that cause CASK to accumulate are correlated to X-linked mental retardation and autism spectrum disorder in humans. I have investigated CASK protein turnover and found that the protein is constantly degraded. This degradation, however, is only partial suggesting that the peptides generated have functions distinct from the full-length polypeptide. Subsequent analyses revealed that these peptides form as a result of CASK being first phosphorylated and then ubiquitinated prior to its limited degradation in the proteasome. During these investigations I identified poly ADP-ribosyl transferase-like 2 (PARP-2) as a protein also degraded through the ubiquitin-proteasome system. PARP-2 degradation occurs when cells are grown in the presence of serum and Ro52 was identified as a candidate E3 ubiquitin ligase required for ubiquitination. Interestingly, when cells are serum-starved, PARP-2 was sequestered to an SDS-insoluble fraction by a yet-to-be identified mechanism. Finally, further investigations with Ro52 revealed that when ectopically expressed, cells develop large circular structures, which I identified to be autophagosomes, the intermediate organelles in autophagy that selectively target ubiquitinated cargo for lysosomal degradation. The RING finger domain of Ro52 and its E3 ligase activity are, however, not required for this process and the deletion of the RING domain does not affect the inclusion and targeting of ubiquitinated proteins to the autophagosomes. Together, these results from studying two disparate proteins, CASK and PARP-2, not only highlight the selective ability of ubiquitination to specify the limited or complete degradation of proteins, but also shed new light on Ro52 as an adaptor involved in the autophagic turnover of proteins in the lysosome.

Download or read book The Ubiquitin System written by Milton J. Schlesinger and published by Cold Spring Harbor Laboratory Press. This book was released on 1988 with total page 218 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Intracellular Protein Degradation written by A.J. Rivett and published by Elsevier Science. This book was released on 1998-08-07 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume brings together a set of reviews that provide a summary of our current knowledge of the proteolytic machinery and of the pathways of protein breakdown of prokaryotic and eukaryotic cells. Intracellular protein degradation is much more than just a mechanism for the removal of incorrectly folded or damaged proteins. Since many short-lived proteins have important regulatory functions, proteolysis makes a significant contribution to many cellular processes including cell cycle regulation and transciptional control. In addition, limited proteolytic cleavage can provide a rapid and efficient mechanism of enzyme activation or inactivation in eukaryotic cells. In the first chapter, Maurizi provides an introduction to intracellular protein degradation, describes the structure and functions of bacterial ATP-dependent proteases, and explores the relationship between chaperone functions and protein degradation. Many of the principles also apply to eukaryotic cells, although the proteases involved are often not the same. Interestingly, homologues of one of the bacterial proteases, Ion protease, have been found in mitochondria in yeast and mammals, and homologues of proteasomes, which are found in all eukaryotic cells (see below), have been discovered in some eubacteria. Studies of proteolysis in yeast have contributed greatly to the elucidation of both lysosomal (vacuolar) and nonlysosomal proteolytic pathways in eukaryotic cells. Thumm and Wolf (chapter 2) describe studies that have elucidated the functions of proteasomes in nonlysosomal proteolysis and the contributions of lysosomal proteases to intracellular protein breakdown. Proteins can be selected for degradation by a variety of differen mechanisms. The ubiquitin system is one complex and highly regulated mechanism by which eukaryotic proteins are targetted for degradation by proteosomes. In chapter 3, Wilkinson reviews the components and functions of the ubiquitin system and considers some of the known substrates for this pathway which include cell cycle and transcriptional regulators. The structure and functions of proteosomes and their regulatory components are described in the two subsequent chapters by Tanaka and Tanahashi and by Dubiel and Rechsteiner. Proteasomes were the first known example of threonine proteases. They are multisubunit complexes that, in addition to being responsible for the turnover of most short-lived nuclear and cytoplasmic protein, are also involved in antigen processing for presentation by the MHC class I pathway. Recent studies reviewed by McCracken and colleagues (chapter 6) lead to the exciting conclusion that some ER-associated proteins are degraded by cytosolic proteasomes. Lysosomes are responsible for the degradation of long-lived proteins and for the enhanced protein degradation observed under starvation conditions. In chapter 7 Knecht and colleagues review the lysosomal proteases and describe studies of the roles of lysosomes and the mechanisms for protein uptake into lysosomes. Methods of measuring the relative contribution of different proteolytic systems (e.g., ubiquitin-proteasome pathway, calcium-dependent proteases, lysosomes) to muscle protein degradation, and the conclusions from such studies, are reviewed by Attai and Taillinder in the following chapter. Finally, proteases play an important role in signaling apoptosis by catalyzing the limited cleavage of enzymes. Mason and Beyette review the role of the major players, caspases, which are both activated by and catalyze limite proteolysis, and also consider the involvement of other protoelytic enzymes in this pathway leading cell death.

Download or read book Cellular Proteolytic Systems written by Aaron J. Ciechanover and published by Wiley-Liss. This book was released on 1994-11-03 with total page 256 pages. Available in PDF, EPUB and Kindle. Book excerpt: The field of cellular proteolysis is advancing rapidly and has great potential impact in a variety of research and clinical areas, including AIDS and cancer research and treatment. The editors, pioneers in the field of cellular and protein research, describe our current understanding of the three major cellular proteolytic systems: the ubiquitin system, the lysosomal and vacuolar systems, and physiological and pathophysiological cellular proteolysis.

Download or read book The Liver written by Irwin M. Arias and published by John Wiley & Sons. This book was released on 2020-03-09 with total page 1156 pages. Available in PDF, EPUB and Kindle. Book excerpt: Bridging the gap between basic scientific advances and the understanding of liver disease — the extensively revised new edition of the premier text in the field. The latest edition of The Liver: Biology and Pathobiology remains a definitive volume in the field of hepatology, relating advances in biomedical sciences and engineering to understanding of liver structure, function, and disease pathology and treatment. Contributions from leading researchers examine the cell biology of the liver, the pathobiology of liver disease, the liver’s growth, regeneration, metabolic functions, and more. Now in its sixth edition, this classic text has been exhaustively revised to reflect new discoveries in biology and their influence on diagnosing, managing, and preventing liver disease. Seventy new chapters — including substantial original sections on liver cancer and groundbreaking advances that will have significant impact on hepatology — provide comprehensive, fully up-to-date coverage of both the current state and future direction of hepatology. Topics include liver RNA structure and function, gene editing, single-cell and single-molecule genomic analyses, the molecular biology of hepatitis, drug interactions and engineered drug design, and liver disease mechanisms and therapies. Edited by globally-recognized experts in the field, this authoritative volume: Relates molecular physiology to understanding disease pathology and treatment Links the science and pathology of the liver to practical clinical applications Features 16 new “Horizons” chapters that explore new and emerging science and technology Includes plentiful full-color illustrations and figures The Liver: Biology and Pathobiology, Sixth Edition is an indispensable resource for practicing and trainee hepatologists, gastroenterologists, hepatobiliary and liver transplant surgeons, and researchers and scientists in areas including hepatology, cell and molecular biology, virology, and drug metabolism.

Download or read book Proteostasis and Disease written by Rosa Barrio and published by Springer Nature. This book was released on 2020-04-09 with total page 350 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.

Download or read book The Proteasome in Neurodegeneration written by Leonidas Stefanis and published by Springer Science & Business Media. This book was released on 2007-08-02 with total page 314 pages. Available in PDF, EPUB and Kindle. Book excerpt: In the last 50 years a wealth of information has allowed us to understand the contribution of various regulatory factors that alter mRNA and protein s- thesis to a variety of physiological and pathological conditions. However, such regulation is only one of many factors that contribute to the levels of a given p- tein. One major factor that has been relatively obscure until recently has been the contribution of protein degradation to the regulation of the steady state level of protein expression and protein function. This rapidly evolving field has made a significant mark on the scientific community, as highlighted by the Award of the Nobel Prize in Chemistry for 2004 to Aaron Ciechanover, Avram Hershko and Irwin Rose for their pioneering work on the ubiquitin-proteasome system (UPS) of protein degradation, which is the subject of this volume. In recent years e- dence has been accumulating that suggests a role for UPS function in both ph- iological and pathological settings. In particular, studies have implicated a central role for the UPS in cell cycle regulation, cancer and neurodegeneration. Two points are however worth bearing in mind: First, ubiquitin’s function appears to extend far beyond the UPS and protein degradation; second, there are other important systems of intracellular protein degradation, most notably autophagic systems through the lysosomes, and these may also be involved in disease pat- physiology.

Download or read book Proteasome Inhibitors in Cancer Therapy written by Julian Adams and published by Springer Science & Business Media. This book was released on 2004-05-25 with total page 319 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.

Download or read book Ubiquitin Proteasome System written by Aldrin V. Gomes and published by . This book was released on 2018 with total page 287 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.

Download or read book The Proteasome Ubiquitin Protein Degradation Pathway written by Peter Zwickl and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 222 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume gives an overview of pro tea some-mediated protein degradation and the regulatory role of the ubiquitin system in cellular proteolysis. The first chapter describes the molecular evolution of the proteasome and its associated activators, i. e. , the 20S core, the base and the lid of the 19S cap, and the 11 S regulator. The ensuing chapter gives an overview of the structure and assembly of the 20S proteasome and the regulation of the archaeal proteasome by PAN. The third contribution summarizes our knowledge on the eukaryotic 26S proteasome and its regulation by the 19S regu lator, followed by a chapter devoted to the llS regulator, which elucidates the structural basis for the 11 S-mediated activation of the 20S proteasome. The fifth chapter reviews in detail the role of the proteasome in the immune response. The subsequent chapter of the natural substrates of the gives a comprehensive description proteasome and their recognition by the enzymes of the ubiqui tination machinery. The penultimate chapter rounds up the in formation on intracellular distribution of proteasomes in yeast and mammalian cells, while the last contribution highlights proteasome inhibitors, tools which proved to be very valuable for dissecting the cellular roles of the proteasome and which might turn out to be of pharmacological importance.

Download or read book Macromolecular Protein Complexes III Structure and Function written by J. Robin Harris and published by Springer Nature. This book was released on 2020-11-30 with total page 580 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book covers important topics such as the dynamic structure and function of the 26S proteasome, the DNA replication machine: structure and dynamic function and the structural organization and protein–protein interactions in the human adenovirus capsid, to mention but a few. The 18 chapters included here, written by experts in their specific field, are at the forefront of scientific knowledge. The impressive integration of structural data from X-ray crystallography with that from cryo-electron microscopy is apparent throughout the book. In addition, functional aspects are also given a high priority. Chapter 1 is available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.

Download or read book Autophagy Biology and Diseases written by Zheng-Hong Qin and published by Springer Nature. This book was released on 2019-11-27 with total page 727 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.

Download or read book Ubiquitin Proteasome System written by Matthew Summers and published by BoD – Books on Demand. This book was released on 2019-06-19 with total page 228 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.

Download or read book Signal Transduction Protocols written by Robert C. Dickson and published by Springer Science & Business Media. This book was released on 2008-02-02 with total page 331 pages. Available in PDF, EPUB and Kindle. Book excerpt: In 1995, Signal Transduction Protocols, edited by David A. Kendall and Stephen J. Hill, was published in the Methods in Molecular Biology series. This second edition represents an update to that previous work with an emp- sis on new methodologies that have developed in the last few years. The goal, then and now, is to provide procedures written by experts with first-hand ex- rience in a detail that goes far beyond what is generally encountered in the “methods” section of most journals and thus actually permits a particular p- cedure to be replicated. In addition, we have had as a secondary goal the id- tification of protocols for the assay of general classes of signal transduction components that, ideally, can be adapted to the assay of any member of that class. The ability to do this has resulted in large part from the use of affini- based assays, the ease with which specific proteins can be specifically tagged, and an explosion in the availability of highly specific antibodies from comm- cial sources, especially antibodies raised against signaling proteins of human origin. The number of available approaches is, fortunately for those working in signaling research, far too great to fit within the confines of this volume, so hard choices as to what to include had to be made.

Download or read book Membrane Biogenesis written by Jos A.F. Op den Kamp and published by Springer Science & Business Media. This book was released on 2013-06-29 with total page 474 pages. Available in PDF, EPUB and Kindle. Book excerpt: Many individual aspects of the dynamics and assembly of biological membranes have been studied in great detail. Cell biological approaches, advanced genetics, biophysics and biochemistry have greatly contributed to an increase in our knowledge in this field.lt is obvious however, that the three major membrane constituents - lipids, proteins and carbohydrates- are studied, in most cases separately and that a coherent overview of the various aspects of membrane biogenesis is not readily available. The NATO Advanced Study Institute on "New Perspectives in the Dynamics of Assembly of Biomembranes" intended to provide such an overview: it was set up to teach students and specialists the achievements obtained in the various research areas and to try and integrate the numerous aspects of membrane assembly into a coherent framework. The articles in here reflect this. Statting with detailed contributions on phospholipid structure, dynamics, organization and biogenesis, an up to date overview of the basic, lipidic backbone of biomembranes is given. Extensive progress is made in the research on membrane protein biosynthesis. In particular the post- and co-translational modification processes of proteins, the mechanisms of protein translocation and the sorting mechanisms which are necessary to direct proteins to their final, intra - or extracellular destination have been characterized in detail. Modern genetic approaches were indispensable in this research area: gene cloning, hybrid protein construction, site directed mutagenesis and sequencing techniques elucidated many functional aspects of specific nucleic acid and amino acid sequences.

Download or read book Intracellular Protein Degradation written by A.J. Rivett and published by Elsevier Science. This book was released on 1998-08-07 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume brings together a set of reviews that provide a summary of our current knowledge of the proteolytic machinery and of the pathways of protein breakdown of prokaryotic and eukaryotic cells. Intracellular protein degradation is much more than just a mechanism for the removal of incorrectly folded or damaged proteins. Since many short-lived proteins have important regulatory functions, proteolysis makes a significant contribution to many cellular processes including cell cycle regulation and transciptional control. In addition, limited proteolytic cleavage can provide a rapid and efficient mechanism of enzyme activation or inactivation in eukaryotic cells. In the first chapter, Maurizi provides an introduction to intracellular protein degradation, describes the structure and functions of bacterial ATP-dependent proteases, and explores the relationship between chaperone functions and protein degradation. Many of the principles also apply to eukaryotic cells, although the proteases involved are often not the same. Interestingly, homologues of one of the bacterial proteases, Ion protease, have been found in mitochondria in yeast and mammals, and homologues of proteasomes, which are found in all eukaryotic cells (see below), have been discovered in some eubacteria. Studies of proteolysis in yeast have contributed greatly to the elucidation of both lysosomal (vacuolar) and nonlysosomal proteolytic pathways in eukaryotic cells. Thumm and Wolf (chapter 2) describe studies that have elucidated the functions of proteasomes in nonlysosomal proteolysis and the contributions of lysosomal proteases to intracellular protein breakdown. Proteins can be selected for degradation by a variety of differen mechanisms. The ubiquitin system is one complex and highly regulated mechanism by which eukaryotic proteins are targetted for degradation by proteosomes. In chapter 3, Wilkinson reviews the components and functions of the ubiquitin system and considers some of the known substrates for this pathway which include cell cycle and transcriptional regulators. The structure and functions of proteosomes and their regulatory components are described in the two subsequent chapters by Tanaka and Tanahashi and by Dubiel and Rechsteiner. Proteasomes were the first known example of threonine proteases. They are multisubunit complexes that, in addition to being responsible for the turnover of most short-lived nuclear and cytoplasmic protein, are also involved in antigen processing for presentation by the MHC class I pathway. Recent studies reviewed by McCracken and colleagues (chapter 6) lead to the exciting conclusion that some ER-associated proteins are degraded by cytosolic proteasomes. Lysosomes are responsible for the degradation of long-lived proteins and for the enhanced protein degradation observed under starvation conditions. In chapter 7 Knecht and colleagues review the lysosomal proteases and describe studies of the roles of lysosomes and the mechanisms for protein uptake into lysosomes. Methods of measuring the relative contribution of different proteolytic systems (e.g., ubiquitin-proteasome pathway, calcium-dependent proteases, lysosomes) to muscle protein degradation, and the conclusions from such studies, are reviewed by Attai and Taillinder in the following chapter. Finally, proteases play an important role in signaling apoptosis by catalyzing the limited cleavage of enzymes. Mason and Beyette review the role of the major players, caspases, which are both activated by and catalyze limite proteolysis, and also consider the involvement of other protoelytic enzymes in this pathway leading cell death.

Download or read book Encyclopedia of Signaling Molecules written by Sangdun Choi and published by Springer. This book was released on 2017-12-15 with total page 6330 pages. Available in PDF, EPUB and Kindle. Book excerpt: The second edition of this encyclopedia presents over 400 biologically important signaling molecules and the content is built on the core concepts of their functions along with early findings written by some of the world’s foremost experts. The molecules are described by recognized leaders in each molecule. The interactions of these single molecules in signal transduction networks will also be explored. This encyclopedia marks a new era in overview of current cellular signaling molecules for the specialist and the interested non-specialist alike. Currently, there are more than 30,000 genes in human genome. However, not all the proteins encoded by these genes work equally in order to maintain homeostasis. Understanding the important signaling molecules as completely as possible will significantly improve our research-based teaching and scientific capabilities.