Ubiquitin and proteasome pathways

The paper identifies USP12/46 deubiquitinases that prevent ESCRT-mediated lysosomal degradation of β1 integrin by removing ubiquitin from its cytoplasmic tail in early endosomes.

This study reveals how two F-box proteins, FBXO22 and FBXL17, recognize distinct structural features of the BACH1 BTB dimer under oxidative stress, leading to its ubiquitination and degradation.

The paper identifies ubiquitin variants that inhibit Ube2d2, showing structural and biophysical properties that suggest potential for developing selective E2 enzyme inhibitors.

This study identifies a non-canonical role for prefoldin subunit 5 in proteasome assembly, showing its necessity for Rpt ring subcomplex formation and proteasome activity.

This study identifies the Dsc ubiquitin ligase complex as a quality control mechanism at the Golgi that degrades orphaned proteins by assessing transmembrane domain hydrophobicity.

This study shows that aging reduces proteasome function in mice brains, and enhancing proteasome activity through genetic or pharmacological means improves cognitive and neuromuscular function in aged mice.

ProEnd identifies and catalogs HbYX motif-containing proteins across diverse organisms, revealing their evolutionary conservation and potential role in proteasome interactions.

This study determines the cryo-EM structures of RNF168/UbcH5c-Ub/nucleosome complexes to elucidate the mechanism of H2A K13/K15 site-specific ubiquitination.

This study shows that Ubp2, a DUB, is redox-regulated during oxidative stress in yeast, controlling K63-ub chains on ribosomes and restoring translation post-stress.

This study identifies the p21 RRLIF box as a ubiquitin-independent degron that interacts with the PSMA3 Trapper, regulating p21 degradation and senescence in response to DNA damage.

This study creates di-ubiquitylated H1 variants to show position-dependent stimulation of RNF168, a DNA repair protein, and demonstrates how these variants guide RNF168 recruitment to DNA breaks.

The paper identifies direct substrates of the DUB USP30 using a proximal-ubiquitome workflow combining APEX2 and ubiquitination enrichment.

This study develops a chemical synthesis method to create polyubiquitylated linker histone H1.0, revealing its role in enhancing RNF168-mediated H2A ubiquitylation through structural and biochemical analysis.

The paper identifies a new N-degron pathway regulated by UBR4 and MetAP2, targeting specific N-terminal arginine and lysine residues after methionine removal.

The paper investigates CTLA4 turnover, showing ubiquitylation at K203 and K213 drives lysosomal degradation, with USP8 and HD-PTP modulating this process through distinct mechanisms.

The paper analyzes ubiquitylated peptides to identify spectral features that can improve detection of the dark ubiquitylome in non-tryptic proteomics.

This study identifies that HCV infection promotes PA28γ acetylation and heptamerization, enhancing proteasomal degradation of RNF2 and leading to HOX gene expression.

The paper investigates how linear ubiquitin chains affect the proteome in Drosophila by analyzing proteomic changes in flies expressing chains of different lengths.

This study identifies how geranylgeranylation of FBXO10 enables its targeting to the outer mitochondrial membrane, where it regulates PGAM5 ubiquitination and mitochondrial function.

This study shows proteasome inhibitors are more effective against NSCLC cells with mutant p53 by inducing oxidative stress and mitochondrial apoptosis, suggesting a new therapeutic strategy.

This study reveals the structural steps of human 20S proteasome assembly using cryo-EM, showing how chaperones facilitate intermediate stages and trigger final maturation.

This study uses engineered deubiquitinases to investigate how different polyubiquitin linkages regulate KCNQ1 functional expression and trafficking, revealing distinct roles for each linkage type.

This study identifies JOSD1 as a deubiquitinase that mitigates hepatic proteotoxicity by stabilizing SOCS1 and enhancing cell survival under proteasome inhibitor stress.

This paper introduces a method to degrade proteins using small tags and an artificial bacterial E3 ligase, demonstrating its effectiveness in neurons and mouse brains.

This study shows that nucleic acids can be ubiquitylated by DTX3L, an E3 ligase, and this modification is reversible by DUBs like USP2 and SARS-CoV-2 PLpro.

The paper investigates the mechanism of action of the USP1 inhibitor KSQ-4279 using biochemical assays and cryo-EM, showing it binds to the same site as ML323 but alters protein structure differently.

This study shows NMDAR antagonists like ketamine boost 20S proteasome activity, enhancing protein degradation and potentially treating neurodegenerative diseases.

The paper shows that the ubiquitin-proteasome system degrades Rps26 during high salt stress in yeast, enabling the formation of Rps26-deficient ribosomes and stress resistance.

The paper identifies virus-induced ubiquitination in monocytes, showing it regulates protein localization and inhibits antiviral responses.

This study shows that polyubiquitinated substrates modulate UBQLN2 phase separation in a linkage-dependent manner, affecting proteasome activity and deubiquitination.