Ubiquitin and proteasome pathways

Localization of Human UBE3A Isoform 3 is Highly Sensitive to Amino Acid Substitutions at p.Met21 Position

The paper investigates how amino acid substitutions at position p.Met21 affect the localization of human UBE3A isoform 3, showing high sensitivity to these changes.

Plant-specific adaptations of the CDC48 unfoldase

The paper analyzes the structural and functional differences of Arabidopsis CDC48A compared to animal and fungal CDC48 systems, revealing unique cofactor interactions and evolutionary adaptations in plants.

UBQLN2 facilitates degradation of the retrotransposon protein PEG10 via UBE3A activity

This paper identifies UBQLN2 as a facilitator of PEG10 gag-pol degradation via UBE3A activity, revealing a stepwise mechanism involving UBQLN2 binding and ubiquitination.

The Deubiquitinase USP36 Regulates Growth and Spermatogenesis Through Catalytic-Dependent and -Independent Mechanisms in Drosophila

This study shows that dUSP36 regulates growth and spermatogenesis in Drosophila through both catalytic and non-catalytic mechanisms.

Cancer Drug Bortezomib, a Proteasomal Inhibitor, Triggers Cytotoxicity in Microvascular Endothelial Cells via Multi-Organelle Stress

This study shows Bortezomib induces apoptosis in microvascular endothelial cells through ER and mitochondrial stress, distinct from Carfilzomib, and highlights its toxicity mechanisms.

Probing the structural heterogeneity of Pup ligase PafA using H/D exchange mass spectrometry

This study uses HDX-MS to investigate the oligomeric states and conformational dynamics of PafA, revealing its monomeric and dimeric forms and how nucleotide binding affects its structure and function.

Rab40 GTPases regulate AMBRA1-mediated transcription and cell migration

This study identifies AMBRA1 as a binding partner of Rab40 GTPases, showing that Rab40/CRL5 ubiquitylates AMBRA1 to regulate gene transcription related to cell migration.

Structural insights into Salinosporamide A mediated inhibition of the human 20S proteasome

The paper presents the cryo-EM structure of the human 20S proteasome bound to marizomib, revealing its binding mode and irreversible inhibitory mechanism.

Revealing the unexpected interplay between the Proteasome Activator PA200 and the immunoproteasome

This paper reveals structural and functional differences in PA200 interaction with the immunoproteasome (i20S) compared to the standard proteasome (s20S), showing PA200 enhances i20S activation and regulates its gene expression.

Activation of the 20S proteasome core particle prevents cell death induced by oxygen- and glucose deprivation in cultured cortical neurons

This study shows that activating the 20S proteasome core particle prevents cell death in cortical neurons under oxygen- and glucose-deprivation conditions.

Dynamic regions allosterically connect the USP14 active site with the proteasome interaction surface

This study identifies dynamic loop regions in USP14 that mediate allosteric connections between the active site, Ub binding, and proteasome interaction surfaces, revealing pre-existing networks crucial for function.

Molecular glues that inhibit deubiquitylase activity and inflammatory signalling

The paper identifies first-in-class inhibitors (BLUEs) that selectively inhibit BRISC complex activity by stabilizing an autoinhibited dimer, reducing interferon-stimulated gene expression.

STI1 domain dynamically engages transient helices in disordered regions to drive self-association and phase separation of yeast ubiquilin Dsk2

This study identifies the STI1 domain's role in driving Dsk2 self-association and phase separation through interactions with transient helices in disordered regions, with implications for proteasome condensate formation.

Stability and DNA Methyltransferase Activity of DNMT3A are Maintained by Ubiquitin-Specific Peptidase 11 (USP11) and Sumoylation Countering Degradation

This study identifies USP11 and SUMOylation as critical for maintaining DNMT3A stability and function, offering potential therapeutic strategies for diseases linked to DNMT3A instability.

Structural insights into the ubiquitin independent MIDN-proteasome pathway

This study reveals how MIDN enhances proteasome activity through cryo-EM structures showing its binding to proteasomes and substrates in two conformational states.

A family of bacterial Josephin-like deubiquitinases with an unusual cleavage mode

The paper identifies a new family of bacterial deubiquitinases that cleave ubiquitin before the C-terminal diGly motif, truncating the modifier and leaving a remnant on the substrate.

SUMO4 promotes SUMO deconjugation required for DNA double-strand break repair.

This study identifies SUMO4 as a critical regulator of DNA double-strand break repair by promoting SUMO deconjugation through SENP1 and preventing excessive SUMOylation.

Drug repurposing: halogenated salicylanilides inhibit USP8 catalytic activity and ACTH release by pituitary cells

This study identifies halogenated salicylanilides, including Closantel, as USP8 inhibitors that reduce ACTH secretion in pituitary cells, suggesting therapeutic potential for Cushing's disease and cancer.

Phase Separation Clustering of Poly Ubiquitin Cargos on the Ternary Mixture Lipid Membranes by Synthetically Cross-Linked Ubiquitin Binder Peptides.

The paper investigates how polymeric ubiquitin cargos cluster on lipid membranes through phase separation driven by multivalent binding interactions, showing valency-dependent condensate formation.

DET1 dynamics underlie co-operative ubiquitination by CRL4DET1 COP1 complexes

The paper reports the cryo-EM structure of human DET1 in complex with DDB1-DDA1 and Ube2e2, revealing how DET1 dynamics facilitate COP1 recruitment and ubiquitination.

Discovery of ester-linked ubiquitylation of PARP10 mono-ADP-ribosylation in cells: a dual post-translational modification on Glu/Asp side chains

This paper discovers a new dual post-translational modification, MARUbylation, where PARP10 is mono-ADP-ribosylated and ubiquitylated on Glu/Asp residues, leading to proteasomal degradation.

The binary protein interactome mapping of the Giardia lamblia proteasome lid reveals extra proteasomal functions of GlRpn11

This paper maps the binary protein interactions of Giardia lamblia proteasome lid subunits and identifies how the absence of Rpn12 and Sem1 is compensated by unique interactions, particularly the weak GlRpn11-GlRpn8 interaction, which supports extra proteasomal functions of GlRpn11.

Rapaprotin is Activated by an Endopeptidase to Disassemble 26S Proteasome

This paper identifies rapaprotin as a 26S proteasome assembly inhibitor that is activated by PREP to induce apoptosis and synergizes with proteasome inhibitors in cancer cells.

Cullin-RING ligase BioE3 reveals molecular-glue-induced neosubstrates and rewiring of the endogenous Cereblon ubiquitome

The paper demonstrates that BioE3 can identify endogenous substrates and neosubstrates of Cullin-RING ligases, revealing changes in the ubiquitination landscape upon molecular glue treatment.

Loss-of-function mutations in the dystonia gene THAP1 impair proteasome function by inhibiting PSMB5 expression

This study identifies THAP1 as a regulator of PSMB5 expression, showing that its loss impairs proteasome function and contributes to dystonia.

Distinct modes of coupling between VCP, an essential unfoldase, and deubiquitinases

This study identifies how VCP interacts with DUBs at distinct sites to coordinate ubiquitin removal during protein recycling.

A High Sensitivity Assay of UBE3A Ubiquitin Ligase Activity

This paper develops a fast, sensitive assay for measuring UBE3A ubiquitin ligase activity using fluorescence detection, suitable for preclinical and clinical applications.

Ubiquitin protease Ubp1 cooperates with Ubp10 and Ubp12 to revert Lysine-164 PCNA ubiquitylation at replication forks

This study identifies Ubp1 as a PCNA deubiquitylase that cooperates with Ubp10 and Ubp12 to regulate DNA replication by controlling PCNA ubiquitylation at replication forks.

Reprograming of the ubiquitin ligase Ubr1 by intrinsically disordered Roq1 through cooperating multifunctional motifs

The paper identifies two cooperating motifs in Roq1 that modulate Ubr1 activity, enhancing ubiquitination of both folded and misfolded proteins during proteotoxic stress.

Bclaf1 biomolecular condensates protect nuclear PTK2 from ubiquitin-proteasome system promoting cardiomyocyte survival during oxidative stress