Ubiquitin and proteasome pathways

In vitro characterization of the baker's yeast deubiquitinase Ubp3

This study shows that the catalytic activity of Ubp3, a yeast deubiquitinase, is independent of its interaction partner Bre5, challenging the current model of Bre5-dependent activation.

Identification and characterization of UBA5 inhibitors

This study identifies five novel UBA5 inhibitors through HTS, showing selectivity and efficacy in inhibiting UFMylation, with potential for therapeutic applications in neurodegenerative diseases and cancer.

Resolving hidden stoichiometries in Bacterial proteasome activator (Bpa)-substrate complexes by cryo-EM and charge detection mass spectrometry

This study uses cryo-EM and charge detection mass spectrometry to determine the stoichiometry and structure of Bpa-substrate complexes in Mtb, revealing an undecameric apo form and a Bpa12:HspR2 complex.

The p97 adaptor p47/NSFL1C is necessary for stress granule dissolution after heat stress

This study shows that p47 is required for p97 recruitment to stress granules, which is necessary for their disassembly after heat stress.

A ubiquitin chain-feeding mechanism for BRCA1-A

This study identifies a chain-feeding mechanism in BRCA1-A that explains its preference for long K63-linked ubiquitin chains through avidity and processivity.

Mechanism of K63-linked polyubiquitin recognition and cleavage by the BRCA1-A complex

The paper investigates how the BRCA1-A complex recognizes and cleaves K63-linked polyubiquitin chains, revealing structural and functional mechanisms involved in DNA damage response.

USP8 Controls Proteostasis Pathways in B Cells and Multiple Myeloma

This study investigates the role of USP8 in B-cell development and multiple myeloma, showing its impact on proteostasis and identifying potential therapeutic strategies.

Lysine deficiency within a conserved lysine desert is critical for EEL-1/HUWE1 to support ubiquitin proteasome system function.

This study identifies the critical role of lysine deficiency in EEL-1/HUWE1 for maintaining UPS function by enhancing ubiquitination of pre-ubiquitinated substrates.

BAG6-RNF115 Couples Protein Quality Control with Ribosome Assembly

This study identifies RPL22L1 as a BAG6-RNF115 substrate whose degradation is regulated by its assembly state into the ribosome, revealing a mechanism linking protein quality control to ribosome biogenesis.

Co-sedimentation is the key to the structural investigation of wild-type FAT10

This study uses MAS NMR to investigate the wild-type FAT10 N-domain in complex with NUB1L, showing co-sedimentation improves spectral quality and reveals structural insights.

FAF1 cofactor enhances UFD1/NPL4-p97 unfolding efficiency across ubiquitin chain lengths independent of SUMO2

Identifying endogenous substrates of the 26S proteasome through site-specific photocrosslinking

The paper identifies proteasomal substrates in yeast using photocrosslinking and mass spectrometry, revealing diverse substrates affected by ER stress.

Functional diversification of UBP6 in plant immunity through N-degron pathway regulation

The paper shows that UBP6 cleavage generates a proteoform that stabilizes NPR1 and enhances plant immunity through the N-degron pathway.

Structures of dynamic interactors at native proteasomes by PhIX-MS and cryoelectron microscopy

The paper uses PhIX-MS and cryo-EM to map transient interactions at proteasomes, revealing structural details of proteins like TXNL1 and PSMD5.

A proximity ligation screen identifies SNAT2 as a novel target of the MARCH1 E3 ubiquitin ligase

The paper uses BioID2 to identify SNAT2 as a novel target of MARCH1, showing it is ubiquitinated and negatively regulated by MARCH1.

Molecular basis of ubiquitin-independent recognition and degradation of ODC/Antizyme by the 26S proteasome

This study identifies the mechanism by which antizyme mediates ubiquitin-independent degradation of yODC by the 26S proteasome through structural and biochemical analysis.

Pan-cancer proteogenomic interrogation of the Ubiquitin Proteasome System

Proteogenomic analysis of up to 11 CPTAC cohorts shows ubiquitin-proteasome proteins often diverge from transcripts; TP53-mutant tumors elevate UBR5 protein, while TRIM28 prognosis is lineage-dependent.

ZnF-UBP domains regulate deubiquitinase activity by relieving ubiquitin product inhibition

The paper investigates ZnF-UBP domains in USP DUBs, showing they relieve product inhibition by facilitating Ub release, thereby regulating enzyme activity.

Substrate biasing in UCHL5 proteoforms

This study identifies substrate biasing in UCHL5 proteoforms, showing N-terminal ubiquitination activates the enzyme toward monoubiquitin substrates and regulates debranching activity.

Potential for the Terminal SKP1 Glycosyltransferase to Exert Non-Enzymatic Control of SKP1 in Toxoplasma gondii

This study shows GAT1, a glycosyltransferase, specifically binds monomeric SKP1 in Toxoplasma gondii, altering its dimer/monomer balance and affecting FBP interactions.

The regulation of Protein Phosphatase 4 by FBXO42 is required for cancer cell survival.

This study identifies FBXO42's role in regulating PPP4C and p53 signaling, showing its importance in cancer cell survival through genetic and proteomic analyses.

Cysteine-mediated bortezomib resistance is governed by α-ketoacid availability

This study shows that α-ketoacids enhance the effectiveness of bortezomib by reducing cysteine-mediated detoxification, thereby increasing proteasome inhibition and cytotoxicity.

HERC4 limits oxidative stress-induced DNA damage during bacterial and viral-bacterial infection

The paper identifies HERC4 as a regulator of ROS-induced DNA damage during bacterial and viral-bacterial infections, showing its role in DNA repair and potential as a therapeutic target.

Resolving symmetry-masked allosteric cooperativity in the M. tuberculosis proteasome core particle

This paper demonstrates positive cooperativity between subunits in the M. tuberculosis 20S proteasome core particle by using a hybrid subunit assembly and isotopic-coding strategy to resolve symmetry-masked allostery.

The transmembrane protein TMEM127 regulates activation and fate of an MHC-I degradation complex by WWP2 modifications

This study identifies TMEM127 as a critical regulator of the MHC-I degradation complex by modulating WWP2 activity, offering a target for enhancing antigen presentation in cancer immunology.

Small Structural Variations, Large Functional Consequences: Comparative Analysis Reveals Structural Control of Ubiquitylation Site Selection by BRCA1/BARD1

This study compares structural variations in BRCA1/BARD1 orthologs across species to show how a structural loop affects ubiquitylation site selection and chromatin regulation.

Redox-modulated bacterial deubiquitinase ElaD: Target recognition and suppression of K63-linked polyubiquitin accumulation in yeast.

This study investigates the redox-dependent activity of the bacterial deubiquitinase ElaD and its impact on K63-linked polyubiquitin accumulation and stress responses in yeast.

Small-molecule inhibition of the Orientia tsutsugamushi deubiquitylating enzyme OtDUB impairs bacterial reproduction

This study identifies small-molecule inhibitors of the bacterial deubiquitylating enzyme OtDUB, showing they reduce O. tsutsugamushi infection in cells.

Structure of the E3 ligase CRL2-ZYG11B with substrates reveals the molecular basis for N-degron recognition and ubiquitination

The paper presents Cryo-EM structures of the CRL2-ZYG11B complex with substrates, revealing how ZYG11B recognizes and ubiquitinates Gly/N-degrons to activate the NLRP1 inflammasome.

LRRC58 defines an E3 ubiquitin ligase complex sensitive to cysteine abundance

The paper identifies LRRC58 as a substrate adaptor in a Cul2 E3 ligase complex that regulates CDO1 degradation in response to cysteine availability, preventing ferroptosis and neurodevelopmental defects.