Ubiquitin and proteasome pathways

USP1/UAF1 targets polyubiquitinated PCNA with an exo-cleavage mechanism that enriches for monoubiquitinated PCNA

This study shows USP1/UAF1 cleaves K48 and K63-linked ubiquitin chains on PCNA via exo-cleavage, preferentially enriching monoubiquitinated PCNA, which may influence DNA damage tolerance pathway choice.

Ubiquitin-dependent degradation of p21Waf1/Cip1 is mediated by AMBRA1 to limit DNA replication stress

This study shows that AMBRA1 promotes the ubiquitin-dependent degradation of p21Waf1/Cip1 to prevent DNA replication stress and supports its role as a prognostic marker in medulloblastoma.

Computationally Driven Top-Down Mass Spectrometry of Ubiquitinated Proteins

This paper introduces a computational and experimental method to determine ubiquitin site and chain topology on proteins using top-down mass spectrometry.

Allosteric activation of the SPRTN protease by ubiquitin maintains genome stability

This study shows that ubiquitin activates SPRTN protease to degrade DNA-protein crosslinks, maintaining genome stability and preventing disease.

Bidirectional control of a metabolic transition by the GID ubiquitin ligase

This study identifies Gid11 as a substrate receptor for the GID ubiquitin ligase in budding yeast, revealing its role in regulating metabolic transitions by targeting glycolytic factors during ethanol metabolism.

Identification of RNF114 as ADPr-Ub reader through non-hydrolysable ubiquitinated ADP-ribose

The paper identifies RNF114 as a specific reader of ubiquitinated ADP-ribose using a chemoproteomics approach and validates its interaction with the modified molecule.

Mdm2 restrains the activity of the CRL4Cdt2 E3 ubiquitin ligase to promote cell cycle progression through the G2/M phase

This study shows Mdm2 promotes cell cycle progression through degradation of Cdt2, stabilizing substrates like p21, independent of p53.

The dual ubiquitin binding mode of SPRTN secures rapid spatiotemporal proteolysis of DNA-protein crosslinks

This study identifies a ubiquitin-binding domain in SPRTN that enhances its proteolytic activity towards polyubiquitinated DNA-protein crosslinks.

Mechanism of nascent chain removal by the Ribosome-associated Quality Control complex

The paper presents a cryo-EM structure of the RQC complex from budding yeast, revealing its mechanism for removing stalled peptides from the ribosome.

FBL as a carrier mediate H2Aub degradation in the lysosome-like structures

The paper identifies FBL as a carrier mediating H2Aub degradation in nucleolar lysosome-like structures during glucose starvation, revealing its role in cell cycle regulation and viability.

Unveiling the biochemical catalysis and regulatory mechanisms of the E3-independent E2 enzyme hUBE2O

This study elucidates the catalytic and regulatory mechanisms of hUBE2O, revealing its unique architecture for mono- and polyubiquitination and identifying key residues and zinc ions as regulators.

Structure and Activity of the Essential UCH Family Deubiquitinase DUB16 from Leishmania donovani

This study characterizes DUB16, an essential UCH family deubiquitinase in Leishmania donovani, showing its structure, activity, and potential as a drug target.

Structural mechanism for recognition of E2F1 by the ubiquitin ligase adaptor Cyclin F

The paper determines the structure of Cyclin F-Skp1 complex bound to E2F1 peptide, revealing differences in substrate-binding site and electrostatic interactions compared to Cyclin A.

The equilibrium between two quaternary assembly states determines the activity of SPOP and its cancer mutants

The paper shows that SPOP activity is regulated by the equilibrium between circular double donut structures and linear filaments, with mutations shifting this balance and affecting substrate turnover and localization.

USP37 prevents premature disassembly of stressed replisomes by TRAIP

This study shows that USP37 prevents premature TRAIP-mediated disassembly of stalled replisomes, maintaining genome stability under replication stress.

Structural basis for the midnolin-proteasome pathway and its role in suppressing myeloma

This study reveals the structural basis of the midnolin-proteasome pathway and shows that midnolin downregulation promotes myeloma cell survival by enhancing IRF4 expression.

Engineering a Cell-Based Orthogonal Ubiquitin Transfer Cascade for Profiling the Substrates of RBR E3 Parkin

This study develops an orthogonal ubiquitin transfer cascade to profile Parkin substrates, revealing roles in DNA replication, protein transport, and mitophagy.

Dynamic hotspots in the Uba7 UFD direct UbcH8 recognition

This paper presents the NMR structure and functional analysis of the Uba7 UFD domain and its interaction with UbcH8, revealing structural flexibility and key residues critical for E2 recognition in the ISGylation pathway.

Proteasome Caspase-Like Activity Regulates Stress Granules and Proteasome Condensates

This study shows that proteasome caspase-like activity is essential for stress granule formation and regulates proteasome condensates under stress.

Loss of UFMylation supports prostate cancer metastasis and rewires cell metabolism towards hexosamine biosynthesis

This study shows that loss of UFMylation promotes prostate cancer metastasis by reprogramming glucose metabolism towards hexosamine biosynthesis.

obABPP-HT*: A Precision-Engineered Activity Proteomics Pipeline for the Streamlined Discovery of Deubiquitinase Inhibitors

This paper introduces a high-throughput activity proteomics pipeline for discovering deubiquitinase inhibitors, identifying potent and selective inhibitors with minimal optimization.

Mechanisms of USP18 deISGylation revealed by comparative analysis with its human paralog USP41

This study identifies molecular determinants of USP18's specificity for ISG15 through comparative analysis with its paralog USP41, revealing structural features essential for enzymatic activity.

Mechanism of D-type cyclins recognition by the AMBRA1 E3 ligase receptor

The paper determines the cryo-EM structure of the AMBRA1-DDB1 complex bound to cyclin D1, revealing the molecular mechanism of cyclin D1 recognition and its regulation by phosphorylation.

A Proteolytic Switch: USP5 controls SDE2 function via UBL-directed cleavage

This study identifies USP5 as the protease responsible for cleaving SDE2UBL, revealing a novel regulatory mechanism for SDE2 function through UBL-directed cleavage.

Reciprocal Regulation Between the SCFFBXO24 Ubiquitin E3 Ligase and FoxP1 Protein

This study identifies FBXO24 as the E3 ligase regulating FoxP1 ubiquitination and stability, revealing bidirectional regulation between the ligase and its substrate.

USP37 protects mammalian cells during DNA replication stress by counteracting CUL2-LRR1 and TRAIP

This study identifies USP37's role in protecting mammalian cells from DNA replication stress by counteracting ubiquitylation of the CMG helicase by CUL2LRR1 and TRAIP.

The deubiquitinase Rpn11 functions as an allosteric ubiquitin sensor to promote substrate engagement by the 26S proteasome

This study shows Rpn11 acts as an allosteric ubiquitin sensor in the proteasome, enhancing substrate degradation by stabilizing the proteasome's engagement state.

Employing neutron-encoded monoUbs to study E2/E3 ligase activity and selectivity for assembling Ub chains

The paper develops a mass spectrometry-based assay to screen E2/E3 ligase pairs for their ability to form ubiquitin chains and analyze chain types.

USP37 prevents unscheduled replisome unloading through MCM complex deubiquitination

This study identifies USP37 as a deubiquitinase that prevents premature replisome disassembly by deubiquitinating MCM7, ensuring genome stability and normal cell cycle progression.

Comprehensive degron mapping in human transcription factors

This study maps degrons in human transcription factors, identifies new degrons, and links degron potency to variant effects and transcriptional activation.