Deubiquitinases: From mechanisms to their inhibition by small molecules

Roles and mechanisms of BAP1 deubiquitinase in tumor suppression

(2021) Louis Masclef et al.   CELL DEATH AND DIFFERENTIATION

Deubiquitinating enzyme amino acid profiling reveals a class of ubiquitin esterases

(2021) Virginia De Cesare et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Insert L1 is a central hub for allosteric regulation of USP1 activity

(2021) Shreya Dharadhar et al.   EMBO REPORTS

Ubiquitylation of lipopolysaccharide by RNF213 during bacterial infection

(2021) Elsje G. Otten et al.   NATURE

Structural basis of FANCD2 deubiquitination by USP1−UAF1

(2021) Martin L. Rennie et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Identifying SARS-CoV-2 antiviral compounds by screening for small molecule inhibitors of Nsp3 papain-like protease

(2021) Chew Theng Lim et al.   BIOCHEMICAL JOURNAL

Regulation of ubiquitin and ubiquitin‐like modifiers by phosphorylation

(2021) Nathaniel L. Hepowit et al.   FEBS Journal

Mechanism, specificity, and function of FANCD2‐FANCI ubiquitination and deubiquitination

(2021) Kimon Lemonidis et al.   FEBS Journal

Mechanism of activation and regulation of deubiquitinase activity in MINDY1 and MINDY2

(2021) Syed Arif Abdul Rehman et al.   MOLECULAR CELL

Biochemical characterization of protease activity of Nsp3 from SARS-CoV-2 and its inhibition by nanobodies

(2021) Lee A. Armstrong et al.   PLoS One

Oxygen-dependent asparagine hydroxylation of the ubiquitin-associated (UBA) domain in Cezanne regulates ubiquitin binding

(2020) Julia Mader et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Deubiquitination of NLRP6 inflammasome by Cyld critically regulates intestinal inflammation

(2020) Sandip Mukherjee et al.   NATURE IMMUNOLOGY

Papain-like protease regulates SARS-CoV-2 viral spread and innate immunity

(2020) Donghyuk Shin et al.   NATURE

An evolutionary approach to systematic discovery of novel deubiquitinases, applied to Legionella

(2020) Thomas Hermanns et al.   Life Science Alliance

UCSF ChimeraX : Structure visualization for researchers, educators, and developers

(2020) Eric F. Pettersen et al.   PROTEIN SCIENCE

Activity profiling and crystal structures of inhibitor-bound SARS-CoV-2 papain-like protease: A framework for anti–COVID-19 drug design

(2020) Wioletta Rut et al.   Science Advances

Deubiquitylases in developmental ubiquitin signaling and congenital diseases

(2020) Mohammed A. Basar et al.   CELL DEATH AND DIFFERENTIATION

Structural Basis for the Activation of the Deubiquitinase Calypso by the Polycomb Protein ASX

(2019) Inessa De et al.   STRUCTURE

Kinetic analysis of multistep USP7 mechanism shows critical role for target protein in activity

(2019) Robbert Q. Kim et al.   Nature Communications

Breaking the chains: deubiquitylating enzyme specificity begets function

(2019) Michael J. Clague et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

Differential Oligomerization of the Deubiquitinases USP25 and USP28 Regulates Their Activities

(2019) Florian Sauer et al.   MOLECULAR CELL

Distinct USP25 and USP28 Oligomerization States Regulate Deubiquitinating Activity

(2019) Malte Gersch et al.   MOLECULAR CELL

Metabolic control of BRISC–SHMT2 assembly regulates immune signalling

(2019) Miriam Walden et al.   NATURE

Structural Basis of BRCC36 Function in DNA Repair and Immune Regulation

(2019) Julius Rabl et al.   MOLECULAR CELL

The E3 ligase HOIL-1 catalyses ester bond formation between ubiquitin and components of the Myddosome in mammalian cells

(2019) Ian R. Kelsall et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Drugging an undruggable pocket on KRAS

(2019) Dirk Kessler et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Branching Out: Improved Signaling by Heterotypic Ubiquitin Chains

(2019) Diane L. Haakonsen et al.   TRENDS IN CELL BIOLOGY

Structural insights into the activation of USP46 by WDR48 and WDR20

(2019) Hanwen Zhu et al.   Cell Discovery

Illustrate: Software for Biomolecular Illustration

(2019) David S. Goodsell et al.   STRUCTURE

Advances in Discovering Deubiquitinating Enzyme (DUB) Inhibitors

(2019) Nathan J. Schauer et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of Small Molecule Antagonists of the USP5 Zinc Finger Ubiquitin-Binding Domain

(2019) Mandeep K. Mann et al.   JOURNAL OF MEDICINAL CHEMISTRY

Bacterial DUBs: deubiquitination beyond the seven classes

(2019) Thomas Hermanns et al.   BIOCHEMICAL SOCIETY TRANSACTIONS

Structure and Function of the 26S Proteasome

(2018) Jared A.M. Bard et al.   Annual Review of Biochemistry

Discovery and Characterization of ZUFSP/ZUP1, a Distinct Deubiquitinase Class Important for Genome Stability

(2018) Dominika Kwasna et al.   MOLECULAR CELL

Identification and Structure-Guided Development of Pyrimidinone Based USP7 Inhibitors

(2018) Colin R. O’Dowd et al.   ACS Medicinal Chemistry Letters

A family of unconventional deubiquitinases with modular chain specificity determinants

(2018) Thomas Hermanns et al.   Nature Communications

6-Thioguanine is a noncompetitive and slow binding inhibitor of human deubiquitinating protease USP2

(2018) Shang-Ju Chuang et al.   Scientific Reports

An expanded allosteric network in PTP1B by multitemperature crystallography, fragment screening, and covalent tethering

(2018) Daniel A Keedy et al.   eLife

Small molecule inhibitors reveal allosteric regulation of USP14 via steric blockade

(2018) Yiwei Wang et al.   CELL RESEARCH

Active site alanine mutations convert deubiquitinases into high‐affinity ubiquitin‐binding proteins

(2018) Marie E Morrow et al.   EMBO REPORTS

The structure of the deubiquitinase USP15 reveals a misaligned catalytic triad and an open ubiquitin-binding channel

(2018) Stephanie J Ward et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

OTULIN limits cell death and inflammation by deubiquitinating LUBAC

(2018) Klaus Heger et al.   NATURE

A quaternary tetramer assembly inhibits the deubiquitinating activity of USP25

(2018) Bing Liu et al.   Nature Communications

Discovery of Small-Molecule Inhibitors of Ubiquitin Specific Protease 7 (USP7) Using Integrated NMR and in Silico Techniques

(2017) Paola Di Lello et al.   JOURNAL OF MEDICINAL CHEMISTRY

Structure and Function of Viral Deubiquitinating Enzymes

(2017) Ben A. Bailey-Elkin et al.   JOURNAL OF MOLECULAR BIOLOGY

An AAA Motor-Driven Mechanical Switch in Rpn11 Controls Deubiquitination at the 26S Proteasome

(2017) Evan J. Worden et al.   MOLECULAR CELL

USP7 small-molecule inhibitors interfere with ubiquitin binding

(2017) Lorna Kategaya et al.   NATURE

Molecular basis of USP7 inhibition by selective small-molecule inhibitors

(2017) Andrew P. Turnbull et al.   NATURE

Discovery and characterization of highly potent and selective allosteric USP7 inhibitors

(2017) Gerald Gavory et al.   Nature Chemical Biology

Deubiquitylating enzymes and drug discovery: emerging opportunities

(2017) Jeanine A. Harrigan et al.   NATURE REVIEWS DRUG DISCOVERY

Mechanism and regulation of the Lys6-selective deubiquitinase USP30

(2017) Malte Gersch et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Structural basis for specific cleavage of Lys6-linked polyubiquitin chains by USP30

(2017) Yusuke Sato et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Mechanism and regulation of the Lys6-selective deubiquitinase USP30

(2017) Malte Gersch et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Structural basis for specific cleavage of Lys6-linked polyubiquitin chains by USP30

(2017) Yusuke Sato et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Azaindoles as Zinc-Binding Small-Molecule Inhibitors of the JAMM Protease CSN5

(2016) Eva Altmann et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Ubiquitin modifications

(2016) Kirby N Swatek et al.   CELL RESEARCH

Drugging the undruggables: exploring the ubiquitin system for drug development

(2016) Xiaodong Huang et al.   CELL RESEARCH

Allosteric Activation of Ubiquitin-Specific Proteases by β-Propeller Proteins UAF1 and WDR20

(2016) Heng Li et al.   MOLECULAR CELL

Molecular basis of Lys11-polyubiquitin specificity in the deubiquitinase Cezanne

(2016) Tycho E. T. Mevissen et al.   NATURE

Allosteric inhibition of SHP2 phosphatase inhibits cancers driven by receptor tyrosine kinases

(2016) Ying-Nan P. Chen et al.   NATURE

An atomic structure of the human 26S proteasome

(2016) Xiuliang Huang et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Structural basis for histone H2B deubiquitination by the SAGA DUB module

(2016) M. T. Morgan et al.   SCIENCE

Molecular Understanding of USP7 Substrate Recognition and C-Terminal Activation

(2016) Lionel Rougé et al.   STRUCTURE

Targeted inhibition of the COP9 signalosome for treatment of cancer

(2016) Anita Schlierf et al.   Nature Communications

BAP1/ASXL1 recruitment and activation for H2A deubiquitination

(2016) Danny D. Sahtoe et al.   Nature Communications

An atomic structure of the human 26S proteasome

(2016) Xiuliang Huang et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Ubiquitin C-terminal hydrolases cleave isopeptide- and peptide-linked ubiquitin from structured proteins but do not edit ubiquitin homopolymers

(2015) John S. Bett et al.   BIOCHEMICAL JOURNAL

How pyridoxal 5′-phosphate differentially regulates human cytosolic and mitochondrial serine hydroxymethyltransferase oligomeric state

(2015) Giorgio Giardina et al.   FEBS Journal

Uncovering the Role of Sgf73 in Maintaining SAGA Deubiquitinating Module Structure and Activity

(2015) Ming Yan et al.   JOURNAL OF MOLECULAR BIOLOGY

Mechanism of UCH-L5 Activation and Inhibition by DEUBAD Domains in RPN13 and INO80G

(2015) Danny D. Sahtoe et al.   MOLECULAR CELL

Structural Basis for the Activation and Inhibition of the UCH37 Deubiquitylase

(2015) Ryan T. VanderLinden et al.   MOLECULAR CELL

Higher-Order Assembly of BRCC36–KIAA0157 Is Required for DUB Activity and Biological Function

(2015) Elton Zeqiraj et al.   MOLECULAR CELL

Phosphorylation and linear ubiquitin direct A20 inhibition of inflammation

(2015) Ingrid E. Wertz et al.   NATURE

Structures of CYLD USP with Met1- or Lys63-linked diubiquitin reveal mechanisms for dual specificity

(2015) Yusuke Sato et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Structural Insights into WD-Repeat 48 Activation of Ubiquitin-Specific Protease 46

(2015) Jianping Yin et al.   STRUCTURE

Structures of CYLD USP with Met1- or Lys63-linked diubiquitin reveal mechanisms for dual specificity

(2015) Yusuke Sato et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Structural and Functional Insights to Ubiquitin-Like Protein Conjugation

(2014) Frederick C. Streich et al.   Annual Review of Biophysics

Insights into the Mechanism of Deubiquitination by JAMM Deubiquitinases from Cocrystal Structures of the Enzyme with the Substrate and Product

(2014) Rashmi K. Shrestha et al.   BIOCHEMISTRY

X-ray Structural and Biological Evaluation of a Series of Potent and Highly Selective Inhibitors of Human Coronavirus Papain-like Proteases

(2014) Yahira M. Báez-Santos et al.   JOURNAL OF MEDICINAL CHEMISTRY

Binding of OTULIN to the PUB Domain of HOIP Controls NF-κB Signaling

(2014) Veronique Schaeffer et al.   MOLECULAR CELL

Molecular Basis and Regulation of OTULIN-LUBAC Interaction

(2014) Paul R. Elliott et al.   MOLECULAR CELL

Screening of DUB activity and specificity by MALDI-TOF mass spectrometry

(2014) Maria Stella Ritorto et al.   Nature Communications

OTU Deubiquitinases Reveal Mechanisms of Linkage Specificity and Enable Ubiquitin Chain Restriction Analysis

(2013) Tycho E.T. Mevissen et al.   CELL

OTULIN Antagonizes LUBAC Signaling by Specifically Hydrolyzing Met1-Linked Polyubiquitin

(2013) Kirstin Keusekotten et al.   CELL

Mitoxantrone Targets Human Ubiquitin-Specific Peptidase 11 (USP11) and Is a Potent Inhibitor of Pancreatic Cancer Cell Survival

(2013) Richard A. Burkhart et al.   MOLECULAR CANCER RESEARCH

The linear ubiquitin-specific deubiquitinase gumby regulates angiogenesis

(2013) Elena Rivkin et al.   NATURE

A Strategy for Modulation of Enzymes in the Ubiquitin System

(2013) A. Ernst et al.   SCIENCE

Regulation of A20 and other OTU deubiquitinases by reversible oxidation

(2013) Yogesh Kulathu et al.   Nature Communications

DUB-Resistant Ubiquitin to Survey Ubiquitination Switches in Mammalian Cells

(2013) Miklós Békés et al.   Cell Reports

A BRISC-SHMT Complex Deubiquitinates IFNAR1 and Regulates Interferon Responses

(2013) Hui Zheng et al.   Cell Reports

Discovery of Specific Inhibitors of Human USP7/HAUSP Deubiquitinating Enzyme

(2012) Céline Reverdy et al.   CHEMISTRY & BIOLOGY

Phosphorylation-dependent activity of the deubiquitinase DUBA

(2012) Oscar W Huang et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Deubiquitinases as a Signaling Target of Oxidative Stress

(2012) Xiomaris M. Cotto-Rios et al.   Cell Reports

Length of the active-site crossover loop defines the substrate specificity of ubiquitin C-terminal hydrolases for ubiquitin chains

(2011) Zi-Ren Zhou et al.   BIOCHEMICAL JOURNAL

The Differential Modulation of USP Activity by Internal Regulatory Domains, Interactors and Eight Ubiquitin Chain Types

(2011) Alex C. Faesen et al.   CHEMISTRY & BIOLOGY

Polyubiquitin binding and cross-reactivity in the USP domain deubiquitinase USP21

(2011) Yu Ye et al.   EMBO REPORTS

Design and Characterization of a Potent and Selective Dual ATP- and Substrate-Competitive Subnanomolar Bidentate c-Jun N-Terminal Kinase (JNK) Inhibitor

(2011) John L. Stebbins et al.   JOURNAL OF MEDICINAL CHEMISTRY

An ankyrin-repeat ubiquitin-binding domain determines TRABID's specificity for atypical ubiquitin chains

(2011) Julien D F Licchesi et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Will the Ubiquitin System Furnish as Many Drug Targets as Protein Kinases?

(2010) Philip Cohen et al.   CELL

Structural Basis for Assembly and Activation of the Heterotetrameric SAGA Histone H2B Deubiquitinase Module

(2010) Alwin Köhler et al.   CELL

Severe Acute Respiratory Syndrome Coronavirus Papain-like Novel Protease Inhibitors: Design, Synthesis, Protein−Ligand X-ray Structure and Biological Evaluation

(2010) Arun K. Ghosh et al.   JOURNAL OF MEDICINAL CHEMISTRY

Structural Insights into the Assembly and Function of the SAGA Deubiquitinating Module

(2010) N. L. Samara et al.   SCIENCE

Defining the Human Deubiquitinating Enzyme Interaction Landscape

(2009) Mathew E. Sowa et al.   CELL

K63-specific deubiquitination by two JAMM/MPN+ complexes: BRISC-associated Brcc36 and proteasomal Poh1

(2009) Eric M Cooper et al.   EMBO JOURNAL

Positional-scanning fluorigenic substrate libraries reveal unexpected specificity determinants of DUBs (deubiquitinating enzymes)

(2008) Marcin Drag et al.   BIOCHEMICAL JOURNAL

The Deubiquitinating Enzyme Ataxin-3, a Polyglutamine Disease Protein, Edits Lys63Linkages in Mixed Linkage Ubiquitin Chains

(2008) Brett J. Winborn et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Structural basis for specific cleavage of Lys 63-linked polyubiquitin chains

(2008) Yusuke Sato et al.   NATURE

A noncovalent class of papain-like protease/deubiquitinase inhibitors blocks SARS virus replication

(2008) K. Ratia et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA