Ubiquitination and Sumoylation are two important posttranslational modifications that play pivotal roles in a variety of biological functions. Although Ubiquitination is traditionally viewed as a critical mark targeting proteins for proteasome-dependent degradation, recent studies reveal that it also plays nonproteolytic functions. In contrast, Sumoylation is long thought not to target proteins for degradation, accumulating evidence suggests that it can serve a priming effect prerequisite for ubiquitination, thereby inducing protein ubiquitination and degradation. Thus, there is an important cross-talk between sumoylation and ubiquitination in determining protein fate. Deregulation in these two marks may cause aberrant activity of proteins and in turn contributes to cancer development. In this Research Topic, we accept review articles, perspectives, research articles covering any one or both of these two posttranslational modifications in regulating diverse signal transduction pathways and providing the novel insights in unraveling the puzzle as to how they may regulate cancer progression and metastasis.

This is the first comprehensive book on Smad signal transduction. Forward looking reviews of Smads are provided in a series of 22 cutting-edge chapters. The book is written for an audience with basic understanding of molecular and cell biology. This volume provides an in-depth review of a rapidly developing field and extensive cross-references between chapters are provided.

Plant innate immunity is a potential surveillance system of plants and is the first line of defense against invading pathogens. The immune system is a sleeping system in unstressed healthy plants and is activated on perception of the pathogen-associated molecular patterns (PAMP; the pathogen’s signature) of invading pathogens. The PAMP alarm/danger signals are perceived by plant pattern-recognition receptors (PRRs). The plant immune system uses several second messengers to encode information generated by the PAMPs and deliver the information downstream of PRRs to proteins which decode/interpret signals and initiate defense gene expression. This book describes the most fascinating PAMP-PRR signaling complex and signal transduction systems. It also discusses the highly complex networks of signaling pathways involved in transmission of the signals to induce distinctly different defense-related genes to mount offence against pathogens.

DNA damage response (DDR) is a term that includes a variety of highly sophisticated mechanisms that cells have evolved in safeguarding the genome from the deleterious consequences of DNA damage. It is estimated that every single cell receives tens of thousands of DNA lesions per day. Failure of DDR to properly respond to DNA damage leads to stem cell dysfunction, accelerated ageing, various degenerative diseases or cancer. The sole function of DDR is to recognize diverse DNA lesions, signal their presence, activate cell cycle arrest and finally recruit specific DNA repair proteins to fix the DNA damage and thus prevent genomic instability. DDR is composed of hundreds of spatiotemporally regulated and interconnected proteins, which are able to promptly respond to various DNA lesions. So it is not surprising that mutations in genes encoding various DDR proteins cause embryonic lethality, malignancies, neurodegenerative diseases and premature ageing. The importance of DDR for cell survival and genome stability is unquestionable, but how the sophisticated network of hundreds of different DDR proteins is spatiotemporally coordinated is far from being understood. In the last ten years ubiquitin (ubiquitination) and the ubiquitin-relative SUMO (sumoylation) have emerged as essential posttranslational modifications that regulate DDR. Beside a plethora of ubiqutin and sumo E1-activating enzymes, E2-conjugating enzymes, E3-ligases and ubiquitin/sumo proteases involved in ubiquitination and sumoylation, the complexity of ubiqutin and sumo systems is additionally increased by the fact that both ubiquitin and sumo can form a variety of different chains on substrates which govern the substrate fate, such as its interaction with other proteins, changing its enzymatic activity or promoting substrate degradation. The importance of ubiquitin/SUMO systems in the orchestration of DDR is best illustrated in patients with mutations in E3-ubiquitin ligases BRCA1 or RNF168. BRCA1 is essential for proper function of DDR and its mutations lead to triple-negative breast and ovarian cancers. RNF168 is an E3 ubiquitin ligase, which creates the ubiquitin docking platform for recruitment of different DNA damage signalling and repair proteins at sites of DNA lesion, and its mutations cause RIDDLE syndrome characterized by radiosensitivity, immunodeficiency and learning disability. In addition, recently discovered the ubiquitin receptor protein SPRTN is part of the DNA replication machinery and its mutations cause early-onset hepatocellular carcinoma and premature ageing in humans. Despite more than 700 different enzymes directly involved in ubiquitination and sumoylation processes only few of them are known to play a role in DDR. Therefore, we feel that the role of ubiquitin and the ubiquitin-related SUMO in DDR is far from being understood, and that this is the emerging field that will hugely expand in the next decade due to the rapid development of a new generation of technologies, which will allow us a more robust and precise analyses of human genome, transcriptome and proteome. In this Research Topic we provide a comprehensive overview of our current understanding of ubiquitin and SUMO pathways in all aspects of DDR, from DNA replication to different DNA repair pathways, and demonstrate how alterations in these pathways cause genomic instability that is linked to degenerative diseases, cancer and pathological ageing.

Proteostasis integrates biological pathways controlling biogenesis, trafficking, folding, and degradation of proteins. This book focuses on two protein breakdown/degradation processes (proteolysis), which are part of a normally functioning proteostatic system: the ubiquitin-proteasome system and autophagy. Chapter 2 of this book is freely available as a downloadable Open Access PDF at http://www.taylorfrancis.com under a Creative Commons Attribution-Non Commercial-No Derivatives (CC-BY-NC-ND) 4.0 license.

Epigenetics in Human Disease, Third Edition examines the diseases and conditions on which we have advanced knowledge of epigenetic mechanisms, such as cancer, autoimmune disorders, aging, metabolic disorders, neurobiological disorders and cardiovascular disease. From molecular mechanisms and epigenetic technology to clinical translation of recent research, the nature and applications of the science is presented for those with interests ranging from the fundamental basis of epigenetics to therapeutic interventions for epigenetic-based disorders, with an emphasis throughout on understanding and application of key concepts in new research and clinical practice. Fully revised and up-to-date, this Third Edition discusses topics of current interest in epigenetic disease research, including stem cell epigenetic therapy, bioinformatic analysis of NGS data, epigenetic mechanisms of imprinting disorders, microRNA in cancer, epigenetic approaches to control obesity, epigenetics and airway disease, and epigenetics in cardiovascular disease. Further sections explore online epigenetic tools and datasets; early-life programming of epigenetics in age-related diseases; the epigenetics of addiction and suicide, and epigenetic approaches to regulating and preventing diabetes, cardiac disease, allergic disorders, Alzheimer's disease, respiratory diseases, and many other human maladies. In addition, each chapter now includes chapter summaries, definitions, and vibrant imagery and figures to reinforce understanding, as well as step-by-step methods and disease research case studies. - Includes contributions from leading international investigators involved in translational epigenetic research and therapeutic applications - Integrates methods and applications with fundamental chapters on epigenetics in human disease, along with an evaluation of recent clinical breakthroughs - Presents side-by-side coverage of the basis of epigenetic diseases and treatment pathways - Each chapter updated to include summaries, definitions, and vibrant imagery and figures to reinforce understanding - Features step-by-step methods and disease research case studies to put book concepts into practice

Inflammation is a biological response triggered by different stimuli that has in the body a potentially damaging effect. In certain conditions, such as injury or infection, inflammation is a normal, healthy response. However, inflammatory disorders that result in the immune system attacking the body's own cells or tissues may cause abnormal inflammation, which results in chronic pain, redness, swelling, stiffness, and damage to normal tissues. Mechanisms involved in promoting a number of different inflammatory disorders and their targeting for therapeutic benefit have been one of the hottest topics in last few decades. The two consecutive volumes (119 and 120) dedicated to this subject cover a wide spectrum of inflammatory disorders, mechanisms that are believed to cause them and different strategies for managing the inflammatory diseases. The volume integrates methods for studying inflammatory disorders, mechanisms that trigger these disorders and strategies for managing the inflammatory disorders It contains timely chapters written by well-renown authorities in their field The information provided in the volume is well supported by a number of high-quality illustrations, figures and tables, and targets a very wide audience of specialists, researchers and students

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.