Ubiquitin and proteasome pathways

Functional Spectrum of USP7 Pathogenic Variants in Hao-Fountain Syndrome: Insights into the Enzyme's Activity, Stability, and Allosteric Modulation

This study analyzes 11 USP7 variants in Hao-Fountain syndrome, showing they affect enzyme activity, stability, and substrate recognition, with some variants responsive to an allosteric activator.

Repurposing UBE2W for programmable protein ubiquitylation

This paper introduces UbyW, a platform for site-specific ubiquitylation using UBE2W, enabling efficient production of ubiquitylated proteins and identifying USP15 as a deubiquitylase for Ran K71 monoubiquitylation.

Structural basis for L-isoaspartyl-containing protein recognition by the PCMTD1 cullin-RING E3 ubiquitin ligase

This paper shows PCMTD1, a cullin-RING ligase, recognizes L-isoaspartyl residues and targets damaged proteins for ubiquitylation and degradation.

Editing of the polyubiquitin architecture on the collided ribosome maintains persistent RQC activity

The paper identifies the roles of Ubp2 and Ubp3 in editing polyubiquitin chains on ribosomes to maintain RQC activity.

A novel type of gel-like proteasome condensate induced by toxic protein aggregates

The paper identifies a novel gel-like proteasome condensate, TAADs, that facilitates aggregate clearance but may contribute to neurodegenerative disorders if aggregates persist.

Deltex and RING-UIM E3 ligases cooperate to create a ubiquitin-ADP-ribose hybrid mark on tankyrase, promoting its stabilization

The paper identifies a mechanism where Deltex E3 ligases modify tankyrase with a ubiquitin-MAR hybrid mark, preventing PAR formation and stabilizing tankyrase through interaction with RNF114 and RNF166.

Targeting deubiquitinating enzymes (DUBs) and ubiquitin pathway modulators to enhance host defense against bacterial infections

This study identifies DUB inhibitors that enhance bacterial clearance in Salmonella infections and shows their potential as host-directed therapies against antibiotic-resistant pathogens.

Conformational dynamics of the bacterial E3 ligase SspH1

This study presents the crystal structure of SspH1 and analyzes its conformational dynamics, showing it exists in an open-closed equilibrium with substrate binding modulating state distribution but not inducing major conformational changes.

Development of D-box peptides to inhibit the Anaphase Promoting Complex/Cyclosome

This study develops D-box peptides that inhibit APC/C by binding Cdc20, showing they are more potent than Apcin and can drive protein degradation.

Genotype-by-environment interactions shape ubiquitin-proteasome system activity

The paper investigates how genotype-by-environment interactions influence the ubiquitin-proteasome system activity in yeast by analyzing genetic effects across different environments and substrates.

SUMO E1 covalent allosteric inhibitors modulate polyamine synthesis via the MAT2A-AdoMetDC axis

The paper identifies SUMO E1 covalent allosteric inhibitors that modulate polyamine synthesis through the MAT2A-AdoMetDC axis and show synergistic effects with polyamine inhibitors in T47D cells.

AMPK alters proteasome phosphorylation status and prevents persistent proteasome condensates

This study shows AMPK regulates proteasome phosphorylation and prevents persistent proteasome condensates in yeast by modulating kinase-phosphatase activity.

Ternary complex formation of VCP, VCPIP1 and p47 facilitates Golgi reassembly

This study identifies the structural basis of VCP-VCPIP1-p47 complex formation and demonstrates the role of VCPID in enhancing DUB activity and Golgi reassembly.

Architecture of the UBR4 complex, a giant E4 ligase central to eukaryotic protein quality control

The paper presents the cryo-EM structure of the UBR4 complex, revealing its architecture and mechanism for substrate binding and ubiquitin chain extension in protein quality control.

Elucidating tissue and sub-cellular specificity of the entire SUMO network reveals how stress responses are fine-tuned in a eukaryote

This study creates the first complete SUMO Cell Atlas in eukaryotes, revealing how SUMO components vary spatially and are regulated during stress responses in Arabidopsis roots.

Expression and DNA methylation of 20S proteasome subunits as prognostic and resistance markers in cancer

The paper analyzes the expression and DNA methylation of 20S proteasome subunits across cancers, finding cancer-type dependent survival associations and functional pathway impacts.

EIF3H Regulates ERK-Driven Oncogenic Signaling in Breast Cancer Metastasis

This study identifies EIF3H as a regulator of ERK-driven oncogenic signaling in breast cancer metastasis, showing its role in promoting metastasis and sensitivity to chemotherapy.

Occupancy of the HbYX hydrophobic pocket is sufficient to induce gate opening in the archaeal 20S proteasomes.

This study identifies the Hb group's interaction with the hydrophobic pocket as sufficient to induce gate opening in archaeal 20S proteasomes, revealing a mechanism for proteasome activation.

USP15: the fourth Proteasome-associated DUB

The paper identifies USP15 as a fourth proteasome-associated DUB, showing it binds transiently to proteasomes and selectively disassembles short polyubiquitin chains.

A recombinant expression system for the Plasmodium falciparum proteasome enables structural analysis of its assembly and the design of selective inhibitors

This paper develops a recombinant Pf20S platform for structural analysis and inhibitor design, identifying a selective inhibitor with high potency against Plasmodium falciparum proteasome.

SMURF2/USP7-mediated ubiquitination of KAP1 controls its SUMO E3 ligase activity and chromatin regulation

This study identifies SMURF2 and USP7 as regulators of KAP1 ubiquitination, showing that this dynamic cycle controls KAP1's SUMOylation activity and impacts chromatin structure and cancer progression.

Global Profiling of N-terminal Cysteine-Dependent Degradation Mechanisms

The paper identifies the Cys-Arg/N-degron pathway as a major regulator of the cysteine-commencing proteome, revealing its role in hypoxia-induced metabolic adaptation and cell survival.

Site-Specific Nanobody Inhibitors of the Proteasomal Deubiquitinase UCH37

This paper develops two nanobody inhibitors of UCH37 to separately target its two Ub-processing activities, enabling their independent study.

The E3 ligase HECTD4 regulates COX-2 dependent tumor progression and metastasis

The paper identifies HECTD4 as a tumor and metastasis suppressor that targets COX-2 for degradation, with COX-2 stabilization driving pro-tumorigenic effects in breast cancer.

Structure of the TXNL1-bound proteasome

The paper reports the cryo-EM structure of TXNL1-bound proteasome and identifies interactions critical for stress-induced degradation of TXNL1.

Proteasomal regulation of ASK family kinases dictates cell fate under hyperosmotic stress

This study shows that proteasome activity inactivates ASK3 by degrading ASK1, linking proteasome function to cell survival under hyperosmotic stress.

Deletion of KLHDC3, an E3 ubiquitin ligase complex substrate receptor, leads to obesity in mice.

This study shows that deleting Klhdc3 in mice causes obesity and developmental issues, highlighting its role in regulating protein stability and adiposity.

The mechanism of cell cycle dependent proteasome-mediated CdvB degradation in Sulfolobus acidocaldarius

This study identifies the mechanism of cell cycle-dependent proteasome-mediated CdvB degradation in Sulfolobus acidocaldarius, revealing a role for a novel transcription factor and proteasome-activating nucleotidase.

A microsporidial deubiquitinase blocks ubiquitin transfer from adenylated E1 to human UBE2K ubiquitin conjugating enzyme

The paper identifies ehOTUB1, a microsporidian deubiquitinase that inhibits human UBE2K's ubiquitin conjugation activity by blocking its interaction with the E1 enzyme.

Determine Interaction Affinity Changes of the SUMO E1 Activating Enzymes During SUMO Activation using Quantitative FRET technology

The paper determines the interaction affinity and kinetics of the Aos1-Uba2 heterodimer during SUMO activation using qFRET and SPR, showing increased stability with SUMO and ATP binding.