Journal ArticleDOI
Breaking the chains: structure and function of the deubiquitinases.
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TLDR
DUBs are subject to multiple layers of regulation that modulate both their activity and their specificity, and due to their wide-ranging involvement in key regulatory processes, these enzymes might provide new therapeutic targets.Abstract:
Ubiquitylation is a reversible protein modification that is implicated in many cellular functions. Recently, much progress has been made in the characterization of a superfamily of isopeptidases that remove ubiquitin: the deubiquitinases (DUBs; also known as deubiquitylating or deubiquitinating enzymes). Far from being uniform in structure and function, these enzymes display a myriad of distinct mechanistic features. The small number (<100) of DUBs might at first suggest a low degree of selectivity; however, DUBs are subject to multiple layers of regulation that modulate both their activity and their specificity. Due to their wide-ranging involvement in key regulatory processes, these enzymes might provide new therapeutic targets.read more
Citations
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Journal ArticleDOI
The Ubiquitin Code
David Komander,Michael Rape +1 more
TL;DR: The structure, assembly, and function of the posttranslational modification with ubiquitin, a process referred to as ubiquitylation, controls almost every process in cells.
Journal ArticleDOI
Building ubiquitin chains: E2 enzymes at work.
Yihong Ye,Michael Rape +1 more
TL;DR: The E2s are able to govern the switch from ubiquitin chain initiation to elongation, regulate the processivity of chain formation and establish the topology of assembled chains, thereby determining the consequences of ubiquitylation for the modified proteins.
Journal ArticleDOI
Ubiquitin-binding domains — from structures to functions
TL;DR: New structure-based insights provide strategies for controlling cellular processes by targeting ubiquitin–UBD interfaces with implications for drug design and cell reprograming.
Journal ArticleDOI
The emerging complexity of protein ubiquitination
TL;DR: The present review focuses on the emerging complexity of the ubiquitin system, and reviews what is known about individual chain types, and highlights recent advances that explain how the ubiqu itin system achieves its intrinsic specificity.
Journal ArticleDOI
Mechanisms of Deubiquitinase Specificity and Regulation
TL;DR: This review conceptualizes the many layers of specificity that DUBs encompass to control the ubiquitin code and discusses examples in which DUB specificity has been understood at the molecular level, and provides a framework to tackle lingering questions in DUB biology.
References
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Journal ArticleDOI
De-ubiquitination and ubiquitin ligase domains of A20 downregulate NF-κB signalling
Ingrid E. Wertz,Karen O'Rourke,Honglin Zhou,Michael Eby,L. Aravind,Somasekar Seshagiri,Ping Wu,Christian Wiesmann,Rohan T. Baker,David L. Boone,Averil Ma,Eugene V. Koonin,Vishva M. Dixit +12 more
TL;DR: A novel ubiquitin ligase domain is defined and two sequential mechanisms by which A20 downregulates NF-κB signalling are identified, both of which participate in mediating a distinct regulatory effect.
Journal ArticleDOI
A Genomic and Functional Inventory of Deubiquitinating Enzymes
Sebastian M.B. Nijman,Mark P.A. Luna-Vargas,Arno Velds,Thijn R. Brummelkamp,Annette M.G. Dirac,Titia K. Sixma,René Bernards +6 more
TL;DR: An inventory of the deubiquitinating enzymes encoded in the human genome is presented and the literature concerning these enzymes is reviewed, with particular emphasis on their function, specificity, and the regulation of their activity.
Journal ArticleDOI
A proteomics approach to understanding protein ubiquitination
Junmin Peng,Junmin Peng,Daniel Schwartz,Joshua E. Elias,Carson C. Thoreen,Dongmei Cheng,Gerald T. Marsischky,Jeroen Roelofs,Daniel Finley,Steven P. Gygi +9 more
TL;DR: A proteomics approach to enrich, recover, and identify ubiquitin conjugates from Saccharomyces cerevisiae lysate provides a general tool for the large-scale analysis and characterization of protein ubiquitination.
Journal ArticleDOI
Defining the Human Deubiquitinating Enzyme Interaction Landscape
TL;DR: A global proteomic analysis of Dubs and their associated protein complexes provided the first glimpse into the Dub interaction landscape, places previously unstudied Dubs within putative biological pathways, and identifies previously unknown interactions and protein complexes involved in this increasingly important arm of the ubiquitin-proteasome pathway.
Journal ArticleDOI
Failure to Regulate TNF-Induced NF-κB and Cell Death Responses in A20-Deficient Mice
TL;DR: A20 is critical for limiting inflammation by terminating TNF-induced NF-kappaB responses in vivo and is associated with severe inflammation and cachexia in mice deficient for A20.