Targeted Protein Degradation

Targeted Protein Degradation PDF Author: Angela M. Cacace
Publisher: Humana
ISBN: 9781071616642
Category : Science
Languages : en
Pages : 351

Get Book Here

Book Description
This volume contains a collection of innovative techniques for studying targeted protein degradation. Chapters guide readers through heterobifunctional proteolysis-targeting chimeras (PROTACs) approaches, E3 ligase, E3 ligase-induced ubiquitylation, proteomic approaches, novel degrader molecules, molecular glue, and stabilize binding interaction between a target and E3 ubiquitin ligase. Written in the format of the highly successful Methods in Molecular Biology series, each chapter includes an introduction to the topic, lists necessary materials and reagents, includes tips on troubleshooting and known pitfalls, and step-by-step, readily reproducible protocols. Authoritative and cutting-edge, Targeted Protein Degradation: Methods and Protocols aims to ensure successful results in this emerging field of drug discovery.

Targeted Protein Degradation

Targeted Protein Degradation PDF Author: Angela M. Cacace
Publisher: Humana
ISBN: 9781071616642
Category : Science
Languages : en
Pages : 351

Get Book Here

Book Description
This volume contains a collection of innovative techniques for studying targeted protein degradation. Chapters guide readers through heterobifunctional proteolysis-targeting chimeras (PROTACs) approaches, E3 ligase, E3 ligase-induced ubiquitylation, proteomic approaches, novel degrader molecules, molecular glue, and stabilize binding interaction between a target and E3 ubiquitin ligase. Written in the format of the highly successful Methods in Molecular Biology series, each chapter includes an introduction to the topic, lists necessary materials and reagents, includes tips on troubleshooting and known pitfalls, and step-by-step, readily reproducible protocols. Authoritative and cutting-edge, Targeted Protein Degradation: Methods and Protocols aims to ensure successful results in this emerging field of drug discovery.

Protein Degradation

Protein Degradation PDF Author: R. John Mayer
Publisher: Wiley-VCH
ISBN: 9783527308378
Category : Science
Languages : en
Pages : 393

Get Book Here

Book Description
The first volume in a new series dedicated to protein degradation, this book lays the foundations of targeted protein breakdown via the ubiquitin pathway. The outstanding importance of the ubiquitin pathway has been recognized with the 2004 Nobel Prize in Chemistry for Aaaron Chiechanover, Avram Hershko, and Irwin Rose. Aaron Ciechanover is one of the editors of this series, and Avram Hershko has contributed to the opening chapter of the present volume. Drawing on the the expertise of two Nobel prize winners, this handy reference compiles information on the initial steps of the ubiquitin pathway. Starting out with a broad view of protein degradation and its functions in cellular regulation, it then goes on to examine the molecular mechanisms of ubiquitin conjugation and recycling in detail. All currently known classes of ubiquitin protein ligases are treated here, including latest structural data on these enzymes. Further volumes in the series cover the function of the proteasome, and the roles of the ubiquitin pathway in regulating key cellular processes, as well as its pathophysiological disease states. Required reading for molecular biologists, cell biologists and physiologists with an interest in protein degradation.

Protein Degradation with New Chemical Modalities

Protein Degradation with New Chemical Modalities PDF Author: Hilmar Weinmann
Publisher: Royal Society of Chemistry
ISBN: 1839160772
Category : Medical
Languages : en
Pages : 382

Get Book Here

Book Description
Targeting protein degradation using small molecules is one of the most exciting small-molecule therapeutic strategies in decades and a rapidly growing area of research. In particular, the development of proteolysis targeting chimera (PROTACs) as potential drugs capable of recruiting target proteins to the cellular quality control machinery for elimination has opened new avenues to address traditionally ‘difficult to target’ proteins. This book provides a comprehensive overview from the leading academic and industrial experts on recent developments, scope and limitations in this dynamically growing research area; an ideal reference work for researchers in drug discovery and chemical biology as well as advanced students.

Adverse Effects of Cancer Chemotherapy: Anything New to Improve Tolerance and Reduce Sequelae?

Adverse Effects of Cancer Chemotherapy: Anything New to Improve Tolerance and Reduce Sequelae? PDF Author: Kulmira Nurgali
Publisher: Frontiers Media SA
ISBN: 2889454827
Category :
Languages : en
Pages : 245

Get Book Here

Book Description
Advances in anti-cancer chemotherapy over recent years have led to improved efficacy in curing or controlling many cancers. Some chemotherapy-related side-effects are well recognized and include: nausea, vomiting, bone marrow suppression, peripheral neuropathy, cardiac and skeletal muscle dysfunction and renal impairment. However, it is becoming clearer that some chemotherapy-related adverse effects may persist even in long term cancer survivors. Problems such as cognitive, cardiovascular and gastrointestinal dysfunction, and neuropathy may lead to substantial long term morbidity. Despite improvements in treatments to counteract acute chemotherapy-induced adverse effects, they are often incompletely effective. Furthermore, counter-measures for some acute side-effects and many potential longer term sequelae of anti-cancer chemotherapy have not been developed. Thus, new insights into prevalence and mechanisms of cancer chemotherapy-related side effects are needed and new approaches to improving tolerance and reduce sequelae of cancer chemotherapy are urgently needed. The present Research Topic focuses on adverse effects and sequelae of chemotherapy and strategies to counteract them.

Lysosomal Pathways of Protein Degradation

Lysosomal Pathways of Protein Degradation PDF Author: J Fred Dice
Publisher: CRC Press
ISBN: 149871305X
Category : Science
Languages : en
Pages : 119

Get Book Here

Book Description
Lysosomal Pathways of Protein Degradation looks at cell biology from the view of a lysosome. It summarizes the composition and assembly of lysosomes in mammalian and yeast cells. It also reviews current knowledge about pathways of endocytosis and secretion and how both endocytosed and secreted proteins can be delivered to lysosomes for degradation.

Intracellular Protein Degradation

Intracellular Protein Degradation PDF Author: A.J. Rivett
Publisher: Elsevier Science
ISBN: 9780762303878
Category : Science
Languages : en
Pages : 0

Get Book Here

Book Description
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.

Cell Biology by the Numbers

Cell Biology by the Numbers PDF Author: Ron Milo
Publisher: Garland Science
ISBN: 1317230698
Category : Science
Languages : en
Pages : 399

Get Book Here

Book Description
A Top 25 CHOICE 2016 Title, and recipient of the CHOICE Outstanding Academic Title (OAT) Award. How much energy is released in ATP hydrolysis? How many mRNAs are in a cell? How genetically similar are two random people? What is faster, transcription or translation?Cell Biology by the Numbers explores these questions and dozens of others provid

Platform Technologies in Drug Discovery and Validation

Platform Technologies in Drug Discovery and Validation PDF Author:
Publisher: Academic Press
ISBN: 0128130709
Category : Medical
Languages : en
Pages : 692

Get Book Here

Book Description
Platform Technologies in Drug Discovery and Validation, Volume 50, the latest release in the Annual Reports in Medicinal Chemistry series, provides timely and critical reviews of important topics in medicinal chemistry, with an emphasis on emerging topics in the biological sciences. Topics covered in this new volume include DELT, Oligos: ASO, siRNA, CRISPR, Micro-fluidic chemistry, High throughput screening, Kinase-centric computational drug development, Virtual Screening, Phenotypic screening, PROTACS, Chemical Biology, Fragment-based lead generation, Antibody-Drug Conjugates, Antibody-recruiting small molecules, Deuteration, and Peptides. - Unique for its treatment of platform technologies for medicinal chemistry and target validation - Provides a single, rich volume that summaries a broad spectrum of expertise relevant to the field - Presents state-of-the-art summaries of platform technologies

Proteasome Inhibitors in Cancer Therapy

Proteasome Inhibitors in Cancer Therapy PDF Author: Julian Adams
Publisher: Springer Science & Business Media
ISBN: 1592597947
Category : Medical
Languages : en
Pages : 319

Get Book Here

Book Description
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.

Ubiquitin-dependent Protein Degradation

Ubiquitin-dependent Protein Degradation PDF Author:
Publisher: Academic Press
ISBN: 9780128186671
Category : Science
Languages : en
Pages : 0

Get Book Here

Book Description
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.