Ubiquitin and proteasome pathways

The paper develops a kinetic model to describe USP14-regulated substrate degradation in the 26S proteasome, showing that USP14 reduces degradation rates and depends on substrate and ATP concentrations.

The paper investigates how TCF25 imposes K48-specificity on Listerin-mediated ubiquitination by interacting with the RING domain and orienting the acceptor ubiquitin.

The paper quantifies UFMylation sites in mouse tissues and ALS patient biopsies, finding increased myosin UFMylation in ALS.

The paper shows that structural ubiquitin contributes to K48 linkage-specificity in Tom1 through a non-canonical binding site identified via cryo-EM.

The paper introduces pLink-UBL, a software tool for identifying UBL modification sites on proteins and small-molecule substrates, and discovers spermidine as a small-molecule substrate of SUMO in fission yeast and mammals.

The paper identifies a new E2 ubiquitin-conjugating enzyme in Plasmodium falciparum using a ubiquitin-activity based probe and validates its function through structural and biochemical analysis.

The paper identifies RING E3 pseudoligases in the TRIM protein family by analyzing their structure and ubiquitin ligase activity, revealing structural divergence that impairs their function.

The paper shows that the host AAA-ATPase VCP/p97 has bacteriolytic activity by mechanically extracting ubiquitinated proteins from bacterial membranes, leading to microbial clearance in a mouse sepsis model.

This paper identifies how Nub1 traps unfolded FAT10 for ubiquitin-independent degradation by the 26S proteasome through a novel mechanism involving structural dynamics and proteasomal engagement.

The paper presents the first high-resolution structure of Mycobacterium tuberculosis 20S core particle in an inactive state, revealing the structural basis for allosteric regulation.

This study demonstrates that HOIL-1 can ubiquitinate non-proteinaceous substrates like saccharides in vitro, identifies a key residue for this activity, and produces ubiquitinated saccharides as potential tools.

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.

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.

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.

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

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

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.

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

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.

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

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

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.

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.

This study identifies Txlnb as a centrosome-adapter protein that mediates proteostasis in cardiomyocytes, linking centrosomes to the ubiquitin-proteasome system and influencing cardiac stress responses.

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.

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.

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

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

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

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.