Ubiquitin and proteasome pathways

Npl4 decodes polyubiquitin length and gates D1-D2 coupling in human VCP/p97

This study investigates how Npl4 decodes polyubiquitin chain length and regulates D1-D2 coupling in human VCP/p97 using smUbiRAD, revealing chain-length thresholds and disease-linked mutations.

Direct observation of ATP-driven ubiquitin chain handling by Cdc48

This study directly observes ATP-driven ubiquitin chain handling by Cdc48, revealing non-processive and processive modes of action and their role in ubiquitin unfolding and chain selection.

The vacuolar tauopathy-associated mutation D395G confers redox sensitivity to p97/VCP

This study investigates how the p97/VCP mutation D395G increases redox sensitivity, leading to oxidative inactivation and contributing to neurodegeneration.

Mechanisms of USP7/MAGEL2 Complex Assembly and Its Mutational Disruption in Neurodevelopmental Diseases

This study investigates the assembly mechanism of the USP7/MAGEL2 complex and identifies mutations that disrupt its formation, linking it to neurodevelopmental diseases.

Phosphorylated ubiquitin is a secondary messenger and an epigenetic mark mediating mitochondria to nucleus signaling

This study identifies phosphorylated ubiquitin (pS65Ub) as a signaling molecule that mediates mitochondrial-to-nuclear communication by modulating histone ubiquitination and gene expression in Parkinson's disease.

BAG6 and RNF126 promote the degradation of cytosolic misfolded proteins that contain buried degron motifs

The paper identifies BAG6 and RNF126 as key components in the degradation of cytosolic misfolded proteins containing buried degron motifs.

A functional triangle relationship of topoisomerase IIβ, BARD1, and ERK2 in immediate early gene transcription

The paper identifies a functional regulatory circuit involving TOP2B, BARD1, and ERK2 in IEG transcription, showing how their interactions are modulated by ubiquitination and phosphorylation.

Identification of novel ubiquitin receptors on the 26S proteasome by photo-crosslinking mass spectrometry

The paper identifies a novel ubiquitin-binding groove on the yeast 26S proteasome using photo-crosslinking mass spectrometry.

Oxidative stress causes a reversible decrease of deubiquitylases activity in old vertebrate brains

This study shows oxidative stress reduces DUB activity in aging brains, which can be reversed with antioxidants, suggesting a reversible cause of proteostasis decline.

Bendless-mediated K63 ubiquitination modulates cellular signalling to regulate Drosophila hematopoiesis

This study investigates how Bendless-mediated K63 ubiquitination regulates Drosophila hematopoiesis by modulating Wingless and JNK signaling pathways.

Differential regulation of p62-ubiquitin conjugates in neurons versus astrocytes during cellular stress

This study investigates how p62-ubiquitin conjugates are regulated in neurons and astrocytes under different stress conditions, revealing cell-type-specific responses.

Chromatin association promotes UBR5-mediated degradation of Rb

This study shows that phosphorylation stabilizes Rb by promoting its dissociation from chromatin, revealing a mechanism linking chromatin association to protein degradation.

Resolving the Activation Mechanism of the Human 20S Proteasome

This study identifies a conserved leucine in the C-terminus of proteasome activators as essential for gate opening of the human 20S proteasome, with structural and functional evidence supporting its role.

Structural basis of substrate recognition for proteasome degradation by prokaryotic ubiquitin-like protein ligase PafA

The paper determines the structural basis of substrate recognition by PafA, showing that broad specificity arises from dynamic, geometrically compatible interactions rather than sequence-specific binding.

Protein kinase A regulates phosphorylation of UBE2J1 at serine residue S266 in response to glucagon signalling

This study identifies phosphorylation of UBE2J1 at S266 by protein kinase A in response to glucagon signaling, distinct from S184 phosphorylation during UPR.

Global analysis of cancer cell responses to USP9X inhibition

This study identifies WEHI-092, a USP9X inhibitor, and shows it arrests cancer cells in metaphase, suggesting USP9X inhibitors could be selective mitotic poisons.

Ubiquitination regulates granulostasis and DRiP accumulation in SGs under heat stress via the E3 ligase MKRN2

This study identifies MKRN2 as an E3 ligase that regulates stress granule dynamics by preventing DRiP accumulation through ubiquitination under heat stress.

Phosphorylation of Ube2J1 at serine S184 is regulated by protein phosphatase 2A.

The paper shows that phosphorylation of Ube2J1 at S184 is regulated by protein phosphatase 2A and affects its proteasomal degradation sensitivity.

Dynamic UFMylation governs cellular fitness by coordinating multi-organelle proteostasis

The paper shows that dynamic UFMylation maintains cellular fitness by coordinating multi-organelle proteostasis through alanine-dependent mechanisms.

Ubiquitin-dependent recruitment of SLFN11 to chromatin is regulated by deubiquitinase and RNF168

The paper identifies that DUB inhibitors and RNF168-mediated ubiquitylation drive SLFN11 chromatin recruitment, particularly at promoters, and that this process is suppressed by TAK243.

Identification and Validation of an Interaction between the E3 Ubiquitin Ligase WWP1 and the Transcriptional Co-Activator WBP2 in the Human Heart

The paper identifies and validates a protein-protein interaction between WWP1 and WBP2 in the human heart using yeast-two hybrid screening and immunofluorescence.

Oncogenic E3-ligase adaptors MAGE-A3/6 promote cancer cell migration via BAP18 degradation

This study identifies BAP18 as a substrate of MAGE-A3/6, showing its degradation promotes cancer cell migration in both cell lines and human tissues.

Targeting CBL ubiquitin ligase activation to downregulate tyrosine kinase signalling

This study demonstrates that activating CBL ubiquitin ligase via engineered mutants or small molecules can downregulate tyrosine kinase signaling by enhancing substrate ubiquitination and reducing downstream signaling.

UFMylation of Pyruvate Dehydrogenase Regulates Mitochondrial Metabolism

This study identifies UFMylation of PDH as a regulator of mitochondrial metabolism, showing it enhances pyruvate oxidation and TCA cycle activity.

UFD1 Recognition of Initiator and Proximal Ubiquitin Drives p97-Mediated Substrate Unfolding enhanced by FAF1, FAF2, and UBXD7

The paper elucidates how UFD1 recognizes initiator and proximal ubiquitin to drive p97-mediated substrate unfolding, with accessory adaptors enhancing this process.

Molecular determinants underlying substrate receptor specificity of human CRL4B E3 ubiquitin ligase

This study identifies molecular determinants that guide DCAF specificity for CUL4B in the CRL4B E3 ubiquitin ligase complex through structural and biochemical analyses.

UBE3C retrofits the proteasome to enforce degradation of ultra-stable folds

This study reveals how UBE3C reprograms the proteasome to degrade ultra-stable protein folds by bypassing USP14 and enhancing substrate unfolding.

Investigating the activity of Varicella Zoster Virus (VZV) SUMO-targeted Ubiquitin Ligase ORF61

This study investigates how VZV ORF61 interacts with SUMOylated proteins and reveals its role as a SUMO-targeted ubiquitin ligase by utilizing the E2D family for ubiquitination.

CDK/mTOR-dependent phosphorylation of UBE2H restrains its charging with ubiquitin and regulates CTLH-dependent degradation

The paper identifies CDK/mTOR-dependent phosphorylation of UBE2H as a regulator of CTLH E3 ligase activity, showing how it controls ubiquitylation and substrate degradation.

A bacterial effector blocks SUMOylation by steric occlusion of UBC9 via arginine-GlcNAcylation

This study identifies SseK1 as a bacterial effector that inhibits host SUMOylation by modifying UBC9, impairing immune responses and aiding Salmonella survival.