Deubiquitinases

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Deubiquitinases

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Author : Julie Maupin-Furlow
language : en
Publisher: Springer Nature
Release Date : 2022-11-09

Deubiquitinases written by Julie Maupin-Furlow and has been published by Springer Nature this book supported file pdf, txt, epub, kindle and other format this book has been release on 2022-11-09 with Science categories.

This book aims to advance the understanding of deubiquitinases (DUBs) and DUB-like enzymes. Chapters detail methods used to identify, classify,and biochemically characterize DUBs along with approaches that enable both the determination and alteration of DUB biological function.. 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, Deubiquitinases: Methods and Protocols aims to be a useful and practical guide to new researchers and experts looking to expand their knowledge.

Chemical Strategies For Investigation Of Deubiquitinases

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Author : Samuel D. Whedon
language : en
Publisher:
Release Date : 2018

Chemical Strategies For Investigation Of Deubiquitinases written by Samuel D. Whedon and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2018 with categories.

Regulation of protein structure and function by post-translational modification is a key mechanism in cellular homeostasis. Among known modifications the small protein ubiquitin is unique in the breadth of functions it directs. Regulation of protein ubiquitylation is the function of more than 600 ligases, and ~100 deubiquitinases. Dysregulated ubiquitylation is involved in infection, inflammation, neurodegeneration, metabolic syndromes and cancer. Therapeutic intervention in these conditions benefits from characterization of substrate-specific ligases and deubiquitinases. Substrate specificity is documented among deubiquitinases, but lags behind knowledge of ligases. In the interest of characterizing specificity of cysteine protease deubiquitinases we have developed chemical methods for site-specific ubiquitylation and electrophile incorporation. We began by developing a ubiquitin-derived electrophile through installation of a C-terminal selenocysteine residue, and orthogonal oxidative conversion to dehydroalanine. Upon validation of the electrophile we expanded our substrate scope to a ubiquitylated peptide, with which we captured the deubiquitinase USP15. In order to access ubiquitylated lysine residues in protein regions inaccessible by native chemical ligation we undertook the synthesis of two selenazolidine amino acids for amber suppression. While conducting amber suppression selections we concurrently pursued semi-synthesis of p53, in order to introduce a C-terminal ubiquitin electrophile. Purification of the semi-synthetic protein proved materially intensive, prompting development of cleavable affinity handles for ligation product purification. A strategy for incorporation at glycine and incorporation at glutamine were developed. A glycine-derived biotin handle proved amenable to reduction by Zn, which furnishes a native glycine, and aromatic thiols, which formed novel site-specific conjugates at the previously modified glycine. Incorporation of a pendant flag tag at glutamine enabled immunoprecipitation followed by traceless tag removal with Zn.

Development Of Cell Permeable Ubiquitin Probes For Investigation Of Deubiquitinases

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Author : Weijun Gui
language : en
Publisher:
Release Date : 2023

Development Of Cell Permeable Ubiquitin Probes For Investigation Of Deubiquitinases written by Weijun Gui and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2023 with categories.

Ubiquitination is a reversible enzymatic post-translational modification system regulates a broad range of cellular processes in eukaryotes. Abnormal function and dysregulation of the ubiquitination system is known to cause a variety of human diseases including neurological disorders, cancer. During last decades, huge success has been achieved in targeting the proteasome system with several FDA approved drugs which tremendously encouraged the development of better and less toxic therapeutics against the human ubiquitination system in treating cancer and neurological disorders. The human genome encodes close to 100 deubiquitinating enzymes (DUBs), which are responsible for removing mono- and poly-ubiquitin from over 5,000 human proteins in cells in order to maintain the normal function and regulation of cells. Moreover, a large number of proteins can interact with DUBs and act as regulators and adaptors of DUBs by regulating the activity and function of DUBs, which further increase the diversity and specificity of DUBs. During the past decades, human DUBs emerging as novel targets for drug development, attract tremendous attention from academic research as well as industrial investment, due to their better-defined active and allosteric sites in comparison to many Ub ligases.

Subcellular Localization Protein Protein Interactions And Therapeutic Targeting Of Human Deubiquitinases

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Author :
language : en
Publisher:
Release Date : 2014

Subcellular Localization Protein Protein Interactions And Therapeutic Targeting Of Human Deubiquitinases written by and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2014 with categories.

Targeting Ubiquitin Chains With Deubiquitinases

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Author : Yu Ye
language : en
Publisher:
Release Date : 2012

Targeting Ubiquitin Chains With Deubiquitinases written by Yu Ye and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2012 with categories.

Yeast Two Hybrid Is An Effective Platform For The Discovery Of Novel Inhibitors Of Human Deubiquitinases

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Author : Natasha Pascoe
language : en
Publisher:
Release Date : 2018

Yeast Two Hybrid Is An Effective Platform For The Discovery Of Novel Inhibitors Of Human Deubiquitinases written by Natasha Pascoe and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2018 with categories.

Deubiquitinating enzymes represent attractive therapeutic targets that can be leveraged towards the treatment of a variety of devastating human health disorders. This doctoral thesis recounts the establishment of the well-studied yeast two-hybrid assay as a novel platform for the discovery of ubiquitin variant inhibitors of human Deubiquitinases. Furthermore, I show that ubiquitin variants isolated against the deubiquitinase USP2 in yeast are capable of binding and inhibiting USP2 function in human cells. Taken together, the work described in this thesis highlights the potential of the two-hybrid system to serve as a method to alleviate a formidable bottle-neck that currently obstructs the development of ubiquitin variants and, in conjunction with currently available in vitro screening methods, offers a platform for the discovery of novel inhibitors against human deubiquitinases.

The Role Of Deubiquitinases In Dna Double Strand Break Repair

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Author : Jun Lu
language : en
Publisher:
Release Date : 2018

The Role Of Deubiquitinases In Dna Double Strand Break Repair written by Jun Lu and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2018 with Science categories.

DNA double-strand break (DSB) is a type of the most critical DNA lesions, and if not repaired promptly, it can result in cell death or a wide variety of genetic alterations including genome instability, large- or small-scale deletions, chromosome loss, loss of heterozygosity, and translocations. DSBs are repaired by double-strand break repair (DSBR), including nonhomologous end-joining (NHEJ) and homologous recombination (HR) pathway, and defects in these pathways cause genome instability and promote tumorigenesis. Accumulating evidence has demonstrated that the superfamily of deubiquitinases (DUBs) can regulate the action and stability of DNA repair enzymes involving in DSBR via modifying ubiquitination levels, a reversible posttranslational modification pathway. In this review, we will discuss ubiquitination/deubiquitination modification involving in DSBR genes, the role of DUBs in DSBR and corresponding mechanisms, and the potential effects of this modification on human diseases.

Conjugation And Deconjugation Of Ubiquitin Family Modifiers

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Author : Marcus Groettrup
language : en
Publisher: Springer Science & Business Media
Release Date : 2011-01-11

Conjugation And Deconjugation Of Ubiquitin Family Modifiers written by Marcus Groettrup and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2011-01-11 with Science categories.

† 1 a a 4 † 17 10 15 ubiquitin; and of 16 VCP 17 18 20 33 34 34 36 p domain. 41 42 42 43 P U 42 47 binding. C. elegans 16 In 21 22 50 51 52 53 13 and UFD 4 10 of Cdc48. 18 30 of Ufd2. COFACTORS 47 23 13 47 47 47 72 15 15 and of Spt23 p90. Ufd2 and Cdc48. In C. elegans 74 16 75 75 76 76 Ufd2 25 54 54 7 56 p47 7 7 80 30 30 81 82 82 but and CD3 26 DUB COFACTORS 30 UFD3 OTU1 4 Cdc48 30 4 OLE1. 15 27 87 REFERENCES 30 REGULATION OF UBIQUITIN MONOUBIQUITINATION UBIQUITINATION 1 32 7 S) d 33 12 13 14 15 18 19 15 20 21 35 15 15 27 15 31 32 31 33 36 monoubiquitination of pol pol 34 37 34 monoubiquitination. 20 35 trans 3 15 REFERENCES by monoubiquitination. Mol Cell; 2009. UBIQUITIN LIGASE ACTIVITY BY Nedd 1 2 of 41 5 6 8 fold. 9 13 14 edd 43 18 18 K M and k 18 22 23 K M 24 25 K M 26 edd 45 18 27 K M K D 18 25 . 8 10 M 21 28 MECHANISM AND REGULATION OF CRLs 34 41 34 edd 47 48 S. pombe 49 51 p27 and I by SCF and SCF 57 58 59 60 CTD CTD CTD CTD in Cul5 CTD CTD CTD 60 18

The Regulation Of Deubiquitinases By Oxidative Stress In Saccharomyces Cerevisiae

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Author : Faye Elizabeth Jade Curtis
language : en
Publisher:
Release Date : 2019

The Regulation Of Deubiquitinases By Oxidative Stress In Saccharomyces Cerevisiae written by Faye Elizabeth Jade Curtis and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2019 with categories.

The Role Of Deubiquitinases In Invasive Migration And Epithelial Integrity In Drosophila

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Author : Hammed Badmos
language : en
Publisher:
Release Date : 2021

The Role Of Deubiquitinases In Invasive Migration And Epithelial Integrity In Drosophila written by Hammed Badmos and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2021 with categories.