Ubiquitin and proteasome pathways

Refined USP25/28 inhibitors with enhanced selectivity towards c-Myc driven squamous lung cancer cells

This study develops refined USP25/28 inhibitors that selectively target c-MYC driven squamous lung cancer cells with reduced off-target effects and toxicity.

Systemic degradation of repressive transcription factors gates gene expression and cell fate specification

The paper shows proteasomes degrade repressive transcription factors, freeing chromatin for activator binding and enabling gene expression and cell fate decisions.

Proteome-wide ubiquitinome profiling reveals substrate-specific dynamics within the USP7 network

This study uses proteomics to show that USP7's deubiquitylation effects are substrate-specific, revealing its role in neurodevelopment and tumor suppression.

MYC-Driven Activation of USP39 Enhances SRSF1 Stability and Promotes PDAC Progression

The paper identifies a MYC-USP39-SRSF1 regulatory axis in PDAC that stabilizes SRSF1 and promotes tumor progression, suggesting USP39 as a therapeutic target.

Regulation of proteasome activation by a ubiquitin-independent feedback mechanism

This study identifies ZFAND5/6 as ubiquitin-independent proteasome activators that regulate NF-κB signaling by degrading UBCH5c.

The EF-hand domain of MINDY3 is a Ubiquitin and RAD23 UBL-binding domain

This paper identifies the EF-hand domain of MINDY3 as a ubiquitin and RAD23 UBL-binding domain, revealing its role in DNA damage response regulation.

Distinct Proteasomal Pathways Drive Oncogenic PPM1D Activation

This study shows that truncating mutations in PPM1D shift its degradation pathway from ubiquitin-independent to UBR5-mediated, leading to increased PPM1D levels and oncogenic effects.

Transcription factor CCTF1 plays a decisive role in regulating the proteasome activity during archaeal cell division

The paper identifies CCTF1 as a key regulator of proteasome activity during archaeal cell division by controlling PAN expression through promoter binding.

Structural basis for regulation of the proteasome 20S core particle by the Parkinsonism-associated proteins FBXO7 and PI31

This study reveals how FBXO7 and PI31 regulate the proteasome 20S core particle and how disease variants disrupt this function.

Repurposing of the assembly chaperone PAC1-PAC2 defines a specialized proteasome landscape in mature mammalian sperm

This study identifies a specialized proteasome structure in mature mammalian sperm using cryo-EM, revealing that PAC1/2 repurposes from a chaperone to a stable regulator, defining a hyperactive 20S variant.

Chaperones shape the conformational landscape of 26S-proteasome-base assembly for allosteric ATPase motor activation

This study reveals how chaperones guide the conformational transitions of the 26S proteasome base subcomplex through intermediates to achieve ATPase activity.

Blm10 scaffolds 14-3-3 adaptors to the proteasome, and maintains cellular proteostatic balance and gamete quality

This study identifies Blm10 as a proteasome-associated protein that modulates proteasome activity and maintains proteostasis and gamete quality in yeast.

Conditional stability of HY5 through the ATE N-degron pathway regulates environmental responses in Arabidopsis thaliana

Faf1 accelerates p97-mediated protein unfolding by promoting ubiquitin engagement

This study identifies Faf1's role in enhancing p97-mediated ubiquitin-dependent protein unfolding by stabilizing the Ufd1-Npl4 cofactor through its UBX domain.

Identification, optimization, and structural elucidation of chloroacetamide scaffold as covalent inhibitors for Ubiquitin C-terminal Hydrolase L3

This study identifies and optimizes a chloroacetamide scaffold as a covalent inhibitor for UCHL3, supported by structural and biochemical validation.

Interplay of Cullin5-HECTD3 ubiquitin ligases regulates stability of CRAF mutant associated with hypertrophy

The paper identifies HECTD3 and Cul5-HECTD3 axis regulation of CRAF mutant stability in hypertrophy, showing Hsp90 primes substrates for ubiquitination and Cul5 controls ligase turnover.

Site-specific combinatorial ubiquitination drives the targeted degradation of plasma membrane proteins

This study identifies ubiquitination sites on RTKs that mediate their degradation via CRLs and shows that multiple ubiquitination sites are required for effective degradation.

Verticillium dahliae ubiquitin-specific proteases coordinate key developmental processes and pathogenicity

This study identifies Usp3 and Usp1 as critical deubiquitinases in Verticillium dahliae that regulate developmental processes and pathogenicity by modulating ubiquitination and gene expression.

Design principles of a membrane-spanning ubiquitin ligase

The paper describes the structure and function of a membrane-spanning E3 ubiquitin ligase complex, revealing its role in developmental processes and linking mutations to human birth defects.

USP7 inhibition perturbs proteostasis and tumorigenesis in triple negative breast cancer

This study shows USP7 inhibition disrupts proteostasis and tumor growth in triple negative breast cancer by stabilizing E3 ubiquitin ligases and affecting DNA repair pathways.

Residue-specific dominant-negative mutant of ubiquitin reveals functional selectivity as Ubp14 deubiquitinase inhibitor

The paper identifies a residue-specific dominant-negative ubiquitin mutant that selectively inhibits Ubp14 deubiquitinase activity, revealing functional selectivity in proteostasis regulation.

Intermolecular β-sheet formation guides the interaction between ubiquitin-like modifier FAT10 and adapter protein NUB1L

The paper investigates the interaction between FAT10 and NUB1L using NMR spectroscopy, revealing that FAT10 adopts an intermolecular β-sheet upon binding, which stabilizes it in an unfolded state for proteasomal degradation.

Systematic Discovery of Motif-based Interactions of the Auxiliary Domains of USP Family Deubiquitinases

The paper systematically identifies SLiM-binding interactions of USP family auxiliary domains using proteomic and biochemical methods, revealing functional redundancy and motif specificity.

Molecular basis for C-degron recognition by the SCFDas1 ubiquitin ligase

The paper investigates how the SCFDas1 ubiquitin ligase recognizes C-terminal degrons, identifying a conserved binding site and key residues involved in substrate recognition.

Proteasome-dependent degradation and nucleus-vacuole junctions sustain proteostasis during acute glucose starvation

The paper shows that proteasome-mediated degradation of misfolded proteins persists during acute glucose starvation in yeast, and nucleus-vacuole junctions support this process under metabolic stress.

Photocrosslinking Activity-Based Probes to Capture the Dynamics of Ubiquitin RING E3 Ligase Interactions

The paper develops a photocrosslinking activity-based probe to study interactions between ubiquitin and RING E3 ligases, confirming existing structures and evaluating new models.

Molecular architecture of meiotic pro-crossover factor HEI10 reveals coupling of higher-order assembly and ubiquitin chain formation

This study determines the molecular structure and function of HEI10, revealing its role in ubiquitin chain formation during meiosis.

Ubiquitinome dynamics and regulation by DUB2 during Leishmania differentiation

This study maps the Leishmania ubiquitinome and identifies DUB2 as a key regulator of differentiation by modulating ubiquitination of proteins involved in cell motility and metabolism.

ASPL-driven subunit exchange remodels VCP/p97 hexamers and is impaired by a multisystem proteinopathy mutation

The paper quantifies VCP hexamer assembly and subunit exchange dynamics, showing that the R155H mutation impairs ASPL-mediated exchange, potentially stabilizing mutant VCP in assemblies.

Cysteine availability tunes ubiquitin signaling via inverse stability of LRRC58 E3 ligase and its substrate CDO1

The paper identifies LRRC58 as a cysteine-responsive E3 ligase that regulates CDO1 stability via ubiquitylation, revealing a mechanism linking cysteine availability to proteasomal turnover.