Ubiquitin and proteasome pathways

The deubiquitinating enzyme Otu1 releases substrates from the conserved initiation complex of the Cdc48/p97 ATPase for proteasomal degradation

The paper shows that Otu1 removes ubiquitin chains from substrates to enable their transfer from Cdc48 ATPase to proteasome for degradation.

Medulloblastoma-Associated KBTBD4 Mutations Disrupt PP2A-A Orphan Quality Control

This study identifies PP2A-A as a target of CRL3KBTBD4, showing that KBTBD4 mutations disrupt PP2A quality control and contribute to medulloblastoma by altering phospho-dependent signaling.

Functional divergence of the Arg/N-degron pathway between the crop Brassica rapa and the model plant Arabidopsis thaliana

This study compares the Arg/N-degron pathway function between Arabidopsis thaliana and Brassica rapa, identifying both conserved and divergent roles in hypoxia and stress responses.

Faf2/Ubx2 potentiates p97/Cdc48 segregase activity via functional priming and reinforcement of the UT3 domain in Ufd1

This study shows Faf2/Ubx2 enhances p97/Cdc48 segregase activity by remodeling its substrate recognition module and priming its motor engagement, enabling efficient substrate processing.

FAF1 and FAF2 enhance human p97-UFD1-NPL4 complex unfoldase activity enabling rational design of p97 activators

This study identifies FAF2 as a strong activator of the p97-UN complex and uses its mechanism to design de novo proteins that enhance p97 activity.

Development of a dual chemical probe for the USP16 and HDAC6 zinc-finger ubiquitin-binding domain

The paper develops a chemical probe targeting the USP16 zinc-finger ubiquitin-binding domain and evaluates its selectivity and activity in cellular assays.

A Structural Code for Assembly Specificity in GID/CTLH-Type E3 Ligases

The paper decodes the structural code governing CRA-CRA pairing in GID/CTLH-type E3 ligases and shows it can be reprogrammed through targeted perturbations.

PA200 differentially regulates the proteasome and inhibits migration of cancer cells

This study shows PA200 regulates proteasome composition and inhibits cancer cell migration, with cell-specific effects on integrin and ECM regulators.

Ubi-SCAPE enables deep exploration of the poly-ubiquitylome

The paper introduces Ubi-SCAPE, a method to purify poly-ubiquitylated proteins with high specificity, reducing contaminants and improving reproducibility.

M1-linked Ubiquitination by LUBAC Regulates AMPK Activity and the Response to Energetic Stress

This study shows LUBAC activates AMPK and OTULIN restricts it, affecting metabolic responses to energy stress in cells, mice, and flies.

Ubiquitin-like SUMO protease expansion in rice (Oryza sativa)

The paper identifies an expansion of SUMO protease genes in cultivated rice, suggesting selective breeding pressure may drive this expansion and its potential role in stress responses.

Structure-guided analysis and prediction of human E2-E3 ligase pairing specificity

The paper predicts functional E2-E3 ligase pairings using structural analysis and machine learning, identifying new interactions and providing a web resource for ubiquitination network mapping.

Orthosteric Molecular Glue Inhibits COP9 Signalosome with Substrate-Dependent Potency

This paper shows that an orthosteric inhibitor of the COP9 signalosome achieves high potency through a molecular glue mechanism that enhances substrate-dependent binding.

Differential higher-order superassembly of HECT-type UBE3 ligases controlled by calcium signals

The paper determines cryo-EM structures of UBE3B and UBE3C in complex with calmodulin, showing how calcium signaling controls their higher-order assembly and activity.

Selective proteasomal degradation from the Golgi apparatus membrane

The paper identifies a mechanism by which misfolded Golgi membrane proteins are ubiquitinated and degraded by the proteasome to prevent Golgi fragmentation.

Structural Basis of CSN-mediated SCF Deneddylation

This study uses cryo-EM to reveal structural intermediates of CSN-mediated SCF deneddylation, providing insights into the mechanism and potential for drug design.

Excess Met1-ubiquitination leads to solid aggregate formation

This study shows that reduced HOIL-1 activity increases Met1-ubiquitin chains, leading to solid protein aggregates and impaired autophagy in neurodegenerative diseases.

Guardian ubiquitin E3 ligases target cancer-associated APOBEC3 deaminases for degradation to promote human genome integrity.

The paper identifies UBR4, UBR5, and HUWE1 as E3 ligases that degrade cancer-associated APOBEC3 proteins to prevent genome mutagenesis.

In vivo kinetics of protein degradation by individual proteasomes

This study uses live-cell single-molecule imaging to show that proteasome substrate processing depends on engagement mode, not just substrate identity or folding.

Proteome-wide C-degron activity profiling connects conditional regulation of the CTLH E3 ligase complex to ribosome biogenesis

The paper identifies C-terminal degron substrates of the CTLH E3 ligase complex and links their regulation to ribosome biogenesis through the chaperone activity of AAMP.

A CK2-FBXW11 kinase-E3 ubiquitin ligase cascade is a metabolic sensor regulating Tryptophan 2,3-dioxygenase stability

The paper identifies a CK2-FBXW11 kinase-E3 ubiquitin ligase cascade that regulates TDO2 stability through Trp-dependent phosphorylation shielding.

Molecular bases for USP48 cis-activity regulation and hyperactivation by Cushing's disease-associated mutations

This study identifies molecular mechanisms by which USP48 mutations in Cushing's disease enhance enzyme activity through structural changes in the catalytic domain and C-terminal region.

Multi-scale classification decodes the complexity of the human E3 ligome

This paper constructs a comprehensive annotated dataset of human E3 ligases and uses a hierarchical classification framework to analyze their functional and structural relationships.

The importance of UBQLN2 ubiquitylation for its turnover and localization

This study shows that ubiquitylation of UBQLN2's UBL domain regulates its stability and localization, with implications for proteasomal degradation and ALS.

TRIM37 recognizes a bipartite degron to ubiquitinate centrosome substrates

The paper identifies a bipartite degron in Cep192 that allows TRIM37 to ubiquitinate and regulate centrosome proteins.

A K27-linked Ubiquitin Checkpoint Controls NOTCH Homeostasis

This study identifies UVRAG as a negative regulator of NOTCH1 by promoting K27-linked ubiquitination and lysosomal degradation, revealing a checkpoint to prevent excessive NOTCH signaling.

Molecular architecture and spatial organisation of proteasomes in the human sperm nucleus

This study uses cryo-ET and cryo-EM to reveal the molecular architecture and spatial organisation of proteasomes in human sperm nuclei, identifying unique features and their role in proteolysis.

Identification of Raptor and GLI1 as USP37 substrates highlight its context-specific function in medulloblastoma cells.

This study identifies Raptor and GLI1 as USP37 substrates, revealing its context-specific roles in medulloblastoma cells as both tumor suppressor and oncogene.

Conformation-specific Antibody Deciphers K27-linked Ubiquitination in Chaperone-Mediated Proteostasis

This paper develops a conformation-specific antibody, K27-IgG, to detect K27-linked polyubiquitin and identifies DNAJB1 as a reader and UBE2Q1 as a writer for this ubiquitin chain type.

Cancer-Associated USP28 Missense Mutations Disrupt 53BP1 Interaction and p53 Stabilization

This study identifies cancer-associated USP28 mutations that disrupt 53BP1 interaction and p53 stabilization, highlighting their role in evading DNA damage responses.