Most proteins undergo post-translational modifications altering physical and chemical properties, folding, conformation distribution, stability, activity and function. Ubiquitin and SUMOs are related small proteins that are members of the large ubiquitin superfamily of post-translational modifiers. Written by highly respected leaders in their fields under the expert guidance of the editor, this volume covers the principles of ubiquitination and SUMOylation, presents detailed reviews of current and emerging concepts and highlights new advances in all areas of SUMOylation and ubiquitination. Topics of note include: the ubiquitin superfamily, the ubiquitin toolbox, onco viral exploitation of the SUMO system, small molecule modulators of desumoylation, mass spectrometry, global proteomic profiling of SUMO and ubiquitin, biotin-based approaches, genetic screening, SUMOylation networks in humans, targets for ubiquitin ligases, regulation of p53, protein homeostasis, miRNAs, DNA replication, DNA damage response, telomere biology, intracellular trafficking, regulation of angiogenesis, brain ischemia, autophagy, assembly and activity, antiviral defense, HIV infection, amyloid and amyloid-like proteins, plant immunity. This comprehensive and up-to-date book is the definitive reference volume on all aspects of SUMOylation and ubiquitination and is an essential acquisition for anyone involved in this area of biology.

This is the second edition of a very well received book that details how the sumoylation system functions and how it modulates numerous cellular activities. SUMO is a post-translational modifier in the ubiquitin super-family that has gained recognition over the last twenty years as an essential and prevalent regulatory molecule. Individual chapters explore the biochemistry, molecular biology, and cell biology of the sumoylation system and its substrate proteins. The book is divided into three themed parts: Molecular Functions (I), Cell Growth Regulation (II), and Diseases (III). Parts I and II focus on the contribution of sumoylation to cellular activities in both the nuclear and cytoplasmic compartments. The nuclear activities covered include nucleic acid metabolism (both RNA and DNA), chromosome structure and replication, and nucleocytoplasmic transport. Cytoplasmic processes presented include regulation of membrane ion channels, general metabolism, and apoptotic signalling. Topics in Part III include the role of sumoylation in developmental abnormalities (craniofacial and cardiovascular), diabetes, neurodegenerative diseases, cancer, and infections with viruses and bacteria. Each of the corresponding chapter authors is an active researcher who has made significant contributions to understanding sumoylation. This second edition provides updates and revisions to most of the original chapters plus adds six new chapters to address important developing areas of sumoylation research. This volume is intended for a scientific audience from undergraduates to independent researchers. The content will serve as both a solid introduction for the novice reader and an in depth treatment for the advanced scholar.

Post-translational protein modifications by members of the ubiquitin family are widely recognized as important regulatory control systems for a variety of biological pathways. Their influence on eukaryotic cellular metabolism is comparable to that of other modifi- tions such as phosphorylation, acetylation and methylation. The small ubiquitin-related modifier SUMO uses a conjugation and de-conjugation system closely related to that of ubiquitin itself; yet, the functions of the SUMO system are highly diverse and largely independent of the ubiquitin system. SUMO modification controls the activity of tr- scription factors and can influence protein stability, but it also contributes to nucleo-cy- plasmic transport, chromosome segregation and DNA damage repair. As a consequence, the SUMO system pervades virtually all areas of basic molecular and cell biology, and scientists from different backgrounds, including medical researchers, are likely to enco- ter SUMO in the course of their studies. This volume, SUMO Protocols, therefore aims at presenting a collection of methods relevant to SUMO research in order to make these tools available to biochemists, molecular and cell biologists as well as research-oriented clinicians not yet familiar with the system. In contrast to the ubiquitin system, which has been the subject of several reviews and methods collections, no practical compendium entirely devoted to SUMO has been p- lished.

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 eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact.

A Comprehensive Guide to Crucial Attributes of Therapeutic Proteins in Biological Pharmaceuticals With this book, Dr. Raju offers a valuable resource for professionals involved in research and development of biopharmaceutical and biosimilar drugs. This is a highly relevant work, as medical practitioners have increasingly turned to biopharmaceutical medicines in their search for safe and reliable treatments for complex diseases, while pharmaceutical researchers seek to expand the availability of biopharmaceuticals and create more affordable biosimilar alternatives. Readers receive a thorough overview of the major co-translational modifications (CTMs) and post-translational modifications (PTMs) of therapeutic proteins relevant to the development of biotherapeutics. The majority of chapters detail individual CTMs and PTMs that may affect the physicochemical, biochemical, biological, pharmacokinetic, immunological, toxicological etc. properties of proteins. In addition, readers are guided on the methodology necessary to analyze and characterize these modifications. Thus, readers gain not only an understanding of CTMs/PTMs, but also the ability to design and assess their own structure-function studies for experimental molecules. Specific features and topics include: Discussion of the research behind and expansion of biopharmaceuticals Twenty chapters detailing relevant CTMs and PTMs of proteins, such as glycosylation, oxidation, phosphorylation, methylation, proteolysis, etc. Each chapter offers an introduction and guide to the mechanisms and biological significance of an individual CTM or PTM, including practical guidance for experiment design and analysis An appendix of biologic pharmaceuticals currently on the market, along with an assessment of their PTMs and overall safety and efficacy This volume will prove a key reference on the shelves of industry and academic researchers involved in the study and development of biochemistry, molecular biology, biopharmaceuticals and proteins in medicine, particularly as biopharmaceuticals and biosimilars become ever more prominent tools in the field of healthcare.

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.

Ubiquitination and Protein Stability - Part B, Volume 619, the latest release in the Methods in Enzymology series, highlights new advances in the field, with this updated volume presenting interesting chapters written by an international board of authors. Topics of note include chapters on Assays of SUMO protease function in mammalian cells, In vitro analysis of proteasome-associated USP14 activity for substrate degradation and deubiquitylation, Methods to study proteasome regulatory particle assembly, Native mass spectrometry approaches to study the proteasome, Single-molecule methods to study the ubiquitin-proteasome system, Assays for the function of ubiquitin in the mammalian endocytic pathway, and much more.

Foreword from the Field Chief Editor, Giuseppe Giaccone Once again Frontiers in Oncology has started the year on a positive note, breaking previous records for submissions and publications, as well as the number of Research Topic article collections posted. The journal continues to grow in size, adding an 18th section focusing on Cancer Metabolism, led by Michael Lisanti and Ubaldo Martinez-Outschoorn, and has brought on a total of five new Chief Editors. Here, introducing Frontiers in Oncology: Quarterly Highlights, we feature a collection of carefully selected articles published during the first quarter of 2019 across the different sections. With a record number of papers to choose from, the papers enclosed in this Special Edition highlight some of the recent advances across the different disciplines. With an array of papers looking at everything from translational research to association studies and clinical trial results, Frontiers in Oncology continues to publish high-quality research from researchers around the world. Many of the recently posted Research Topics in the journal focus on early diagnosis and prevention, as well as the importance of survivorship studies and outcomes of cancer treatment. Consideration of such aspects of cancer research and treatment is pivotal in the global effort towards increased survival rates and improved quality of life. With ASCO 2019 marking the end of Q1 and the transition into Q2, the journal looks forward to the rest of the year, and continuing to play an active role in the research community. Giuseppe Giaccone

This detailed book explores the technical breakthroughs with biophysical and cell biological approaches that have advanced the study of molecular mechanisms underlying the generation and transduction of the hedgehog (HH) signal, indicating the important role of sterols in this pathway. Within its pages, the volume examines techniques involving several key protein components in this pathway, including HH, the signaling ligand; Dispatched, a HH secretion regulator; Patched, the receptor of HH; Smoothened, the signal transducer used to transduce the HH signal across the plasma membrane; and GLI, the transcription factor to turn on HH target genes. Written in the highly successful Methods in Molecular Biology series format, chapters feature introductions to their respective topics, lists of the necessary materials and reagents, step-by-step readily reproducible laboratory protocols, as well as tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Hedgehog Signaling: Methods and Protocols provides researchers in clinical and basic science with a fresh and reliable reference for analyzing HH signal transduction through cell biological, biochemical, and biophysical approaches.