Ubiquitin and proteasome pathways

Structures of Fab-stabilized CHIP reveal a conformational switch important in E3 ligase and chaperone functions

This study determines the structures of CHIP stabilized by Fab antibodies, revealing conformational switches that regulate its E3 ligase and chaperone functions.

CXXC5 is a ubiquitinated protein and is degraded by the ubiquitination-proteasome pathway

The paper identifies CXXC5 as a ubiquitinated protein degraded by the ubiquitin-proteasome pathway, independent of cell cycle phases.

SARS-CoV-2 nsp16 is regulated by host E3 ubiquitin ligases, UBR5 and MARCHF7

This study identifies host E3 ubiquitin ligases UBR5 and MARCHF7 that ubiquitinate and degrade SARS-CoV-2 nsp16, inhibiting viral replication across strains.

A family of E3 ligases extend K11 polyubiquitin on sites of MARUbylation

The paper identifies RNF114 as an E3 ligase that extends K11 polyubiquitin on MARUbylated sites, revealing a novel mechanism of Ub-ADPr recognition and polyubiquitylation.

A complete map of human cytosolic degrons and their relevance for disease

The paper systematically identifies degrons in human cytosolic proteins and links them to disease mechanisms through machine learning and structural analysis.

Phosphorylation of the α subunit inhibits proteasome assembly and regulates cell division in an archaeon

This study shows that phosphorylation of a proteasome subunit by ePK2 inhibits proteasome assembly and regulates cell division in Sulfolobales archaea.

Redox-driven control of Yuh1/UCHL3 impacts mitochondrial health via NEDD8/Rub1 pathway

The paper investigates how redox changes affect Yuh1/UCHL3 activity, revealing a thiol-based redox switch that modulates NEDD8/Rub1 processing and impacts mitochondrial health.

PI31 is a positive regulator of 20S immunoproteasome assembly

The paper identifies PI31 as a positive regulator of 20S immunoproteasome assembly, showing it facilitates the formation of interferon-gamma-induced immuno-proteasomes.

The molecular basis of integrated stress response silencing

This study determines the structure of the human E3 ligase SIFI, revealing its mechanism for ubiquitinating multiple substrates to silence the integrated stress response.

Chimeric deubiquitinase engineering reveals structural basis for specific inhibition of USP30 and a framework for DUB ligandability

This study identifies the structural basis for USP30 inhibition using chimeric protein engineering and provides a framework for designing specific deubiquitinase inhibitors.

In silico analysis and Predictive linkage of Deubiquitinating Enzymes underlying Early Development

This study investigates the role of deubiquitinating enzymes (DUBs) in embryonic stem cell maintenance and differentiation through bioinformatics and experimental approaches, identifying their expression patterns and functional links to developmental pathways.

Pervasive phenotypic effects of Fbxo42 controlled by regulation of PP4 phosphatase

This study identifies FBXO42 as a regulator of PP4 phosphatase activity, showing its role in controlling cellular processes through ubiquitination of PP4.

A kinetic model for USP14 regulated substrate degradation in 26S proteasome

The paper develops a kinetic model to describe USP14-regulated substrate degradation in the 26S proteasome, showing that USP14 reduces degradation rates and depends on substrate and ATP concentrations.

The ribosome-associated quality control factor TCF25 imposes K48 specificity on Listerin-mediated ubiquitination of nascent chains by binding and specifically orienting the acceptor ubiquitin

The paper investigates how TCF25 imposes K48-specificity on Listerin-mediated ubiquitination by interacting with the RING domain and orienting the acceptor ubiquitin.

Site-specific quantification of the in vivo UFMylome reveals myosin modification in ALS

The paper quantifies UFMylation sites in mouse tissues and ALS patient biopsies, finding increased myosin UFMylation in ALS.

Structural ubiquitin contributes to K48 linkage-specificity of the HECT ligase Tom1

The paper shows that structural ubiquitin contributes to K48 linkage-specificity in Tom1 through a non-canonical binding site identified via cryo-EM.

Unique Gluing Effect of ASXL1 K351 Monoubiquitination Stimulates PR-DUB-Mediated Nucleosomal H2AK119Ub Deubiquitination

The paper identifies a unique mechanism by which ASXL1 K351 monoubiquitination enhances PR-DUB activity through structural stabilization, enabling efficient H2AK119Ub deubiquitination.

Salmonella SteD and mammalian SUSD6 use TMEM127 to co-disinhibit the WWP2 E3 ubiquitin ligase

The paper shows that TMEM127 and SUSD6, along with Salmonella SteD, co-disinhibit WWP2 E3 ubiquitin ligase through distinct mechanisms.

Huib32: A Potent and Selective USP32 Inhibitor Modulating Endosomal Processes and Advancing Cell-Permeable USP32 Probes

This paper introduces Huib32, a selective USP32 inhibitor, and two activity-based probes that modulate endosomal processes and provide tools for studying USP32 in cancer and neurodegenerative diseases.

Global analysis of protein and small-molecule substrates of ubiquitin-like proteins (UBLs)

The paper introduces pLink-UBL, a software tool for identifying UBL modification sites on proteins and small-molecule substrates, and discovers spermidine as a small-molecule substrate of SUMO in fission yeast and mammals.

Identification of a new Plasmodium falciparum E2 ubiquitin conjugating enzyme

The paper identifies a new E2 ubiquitin-conjugating enzyme in Plasmodium falciparum using a ubiquitin-activity based probe and validates its function through structural and biochemical analysis.

Uev1A counteracts oncogenic Ras stimuli in both polyploid and diploid cells

The paper identifies Uev1A and its human homologs as protectors against oncogenic Ras-induced cellular stress in both polyploid and diploid cells, showing their role in suppressing tumor growth and improving patient survival.

Mechanism of USP21 autoinhibition and histone H2AK119 deubiquitination

This study determines the structure of USP21 bound to H2AK119ub and identifies phosphorylation-regulated autoinhibition as a mechanism for its activity regulation.

K48-ubiquitin-activated proteases cut-up post-ER proteins

The paper shows that K48- and K63-linked polyubiquitination of post-ER proteins leads to distinct degradation pathways via different proteases.

Identification of RING E3 pseudoligases in the TRIM protein family

The paper identifies RING E3 pseudoligases in the TRIM protein family by analyzing their structure and ubiquitin ligase activity, revealing structural divergence that impairs their function.

Nub1 traps unfolded FAT10 for ubiquitin-independent degradation by the 26S proteasome

This paper identifies how Nub1 traps unfolded FAT10 for ubiquitin-independent degradation by the 26S proteasome through a novel mechanism involving structural dynamics and proteasomal engagement.

High-Resolution Mapping of the Human E3-Substrate Interactome using Ubicon Uncovers Network Architecture and Cancer Vulnerabilities

The paper introduces Ubicon, a deep learning framework for predicting human E3-substrate interactions, revealing network architecture and cancer-related vulnerabilities.

Structural basis for the ubiquitin chain recognition of the human 26S proteasome

The paper determines how the human 26S proteasome distinguishes between K48-linked and K11/K48-branched ubiquitin chains through structural analysis and functional studies.

Structural basis for allosteric regulation of the proteasome core particle

The paper presents the first high-resolution structure of Mycobacterium tuberculosis 20S core particle in an inactive state, revealing the structural basis for allosteric regulation.

The RBR E3 ubiquitin ligase HOIL-1 can ubiquitinate diverse non-proteinaceous substrates in vitro

This study demonstrates that HOIL-1 can ubiquitinate non-proteinaceous substrates like saccharides in vitro, identifies a key residue for this activity, and produces ubiquitinated saccharides as potential tools.