Ubiquitin and proteasome pathways

Synthetic tools to redirect the ubiquitin E3 ligase activity of, PRT1, a plant-specific N-recognin.

The paper introduces synthetic tools to redirect and chemically control the Arg/N-degron pathway by modifying PRT1's substrate recognition and using nanobodies to induce ubiquitination.

Survey of the human proteostasis network: the ubiquitin-proteasome system

The paper provides a comprehensive survey of the ubiquitin-proteasome system (UPS) and estimates its size and scope within the human proteostasis network.

Ubiquitin isopeptidase and esterase activities have distinct catalytic requirements

This study shows that isopeptidase and esterase activities of deubiquitinases have distinct catalytic requirements, with cysteine not strictly needed for esterase activity.

Ubiquitin ligase RNF126 exerts functions in lysosomal damage response and lysosomal homeostasis maintenance

This study identifies RNF126 as a ubiquitin ligase involved in lysosomal damage response and homeostasis, showing its recruitment to lysosomes and role in substrate ubiquitylation.

Targeting proteasome composition reprograms tumor-intrinsic inflammation through selective degradation of STAT1

This study identifies a small molecule targeting PSME4, which stabilizes STAT1 and reprograms tumor inflammation, suppressing tumor growth by altering cytokine signaling.

Identification of active deubiquitinases in dendritic cells under unstimulated and activated conditions.

The paper profiles deubiquitinase (DUB) activity and abundance in dendritic cells under unstimulated and CpG-stimulated conditions using activity-based probes and proteomics.

HECT-type ligases facilitate autoubiquitination and degradation of other ubiquitin ligases to activate plant immunity

This study shows that HECT-type ligases UPL3/4 promote the degradation of other E3 ligases like PUB22, thereby regulating immune-related substrate stability and plant immunity.

Mathematical modeling of SUMOylation reveals tissue-specific and dynamic responses to abiotic stress

The paper uses a mathematical model of the plant SUMO cycle to reveal dynamic and tissue-specific SUMOylation responses to abiotic stress.

Fluorescent Ubiquitination-based Trbl Turnover Indicator (FUTTI): A tool to detect activity of the Tribbles pseudokinase in vivo

The paper introduces FUTTI, a tool to detect Tribbles pseudokinase activity in vivo by using a fluorescent degron sensor that responds to Trbl levels.

Proteasomal surveillance of exposed cysteines

The paper identifies two proteasomal mechanisms that target proteins with exposed cysteines, revealing their role in quality control and linking them to human diseases.

A functional screen for ubiquitin regulation identifies an E3 ligase secreted by Pseudomonas aeruginosa

This study identifies a novel E3 ligase secreted by Pseudomonas aeruginosa that regulates virulence through ubiquitin modification.

An N-Terminally Acetylated Degron Specifically Recognized by the CTLHMKLN1-FAM72A E3 Ubiquitin Ligase for Regulatory Protein Degradation

The paper identifies an N-terminal acetylated degron recognized by the CTLHMKLN1-FAM72A E3 ubiquitin ligase, revealing a specific motif and molecular mechanism for proteasomal degradation.

Structure of Blm10:13S proteasome intermediate reveals parallel assembly pathways for the proteasome core particle

The paper presents cryo-EM structures of a Blm10:13S proteasome intermediate, revealing parallel assembly pathways for the proteasome core particle involving Blm10 and Pba1/Pba2.

Substrate Profiling of RNF216 Uncovers a Translation-Linked OTUD4 Regulatory Axis

The paper identifies RNF216 and OTUD4 as regulators of protein synthesis and degradation, showing their interaction disrupts neurodegeneration in Gordon Holmes syndrome.

Ubiquitin-Derived Diglycine Remnants as Chemical Handles for Chemoenzymatic Proteomics

This paper demonstrates the use of ubiquitin-derived diglycine remnants as chemical handles for chemoenzymatic proteomics, enabling antibody-independent analysis of protein ubiquitination.

Cyclin D-CDK4/6 couple proliferation to membrane and mitochondrial protein supply through a DeSI1 phospho-switch

This study identifies DeSI1 as a cyclin D-CDK4/6 substrate whose phosphorylation regulates membrane and mitochondrial protein supply during proliferation.

Ubp3 mediates dynamic deubiquitination of mitochondria upon induction of mitophagy

This study shows Ubp3 dynamically regulates mitochondrial ubiquitination during mitophagy, revealing its role in ubiquitin storage and release as a stress response mechanism.

Proximity biotinylation at the host-Shigella interface reveals UFMylation as an antibacterial pathway.

The paper identifies UFMylation as an antibacterial pathway using proximity biotinylation and mass spectrometry, showing it targets intracellular Shigella and Salmonella.

Parallel Arg/N-degron recognition systems regulate coenzyme A biosynthesis

The paper identifies PANK1β and PANK3 as substrates of the Arg/N-degron pathway, revealing two distinct E3 ligase systems that regulate CoA biosynthesis through ubiquitin-dependent degradation.

Chemically induced USP21-KLHL12 association recruits USP21 to COPII assembly

The paper shows that BAY-805 induces USP21-KLHL12 association, recruiting USP21 to COPII vesicles and impairing large cargo transport.

Comparative ubiquitinomics of human skin reveals insulin receptor ubiquitination as a regulator of collagen secretion.

The paper identifies insulin receptor ubiquitination as a regulator of collagen secretion in human skin through comparative ubiquitinomics of healthy and CYLD syndrome skin.

Glutamine-regulated VCP acetylation creates a proteostasis vulnerability in RB1-deficient tumor

This study identifies VCP inhibition as a therapeutic strategy for RB1-deficient tumors by revealing glutamine-regulated VCP acetylation as a proteostasis vulnerability.

Multimodal substrate recruitment enables CTLH-MKLN1 E3 ligase to target N-, C-, and internal degrons

This study reveals how MKLN1's discoidin and Kelch domains recognize diverse degrons through multivalent interactions, enabling substrate recruitment by the CTLH-MKLN1 E3 ligase.

A new class of inherently efficient SUMOylation substrates

This paper identifies a new class of inherently efficient SUMOylation substrates by showing that ZBTB38BTB and related BTB domains can be SUMOylated efficiently without E3 ligase involvement.

Gene repertoire expansion and cis-regulatory diversification shaped 26S proteasome evolution within a proteostasis-centered network

This study investigates the evolution of the 26S proteasome in plants by analyzing gene repertoires, cis-regulatory elements, and regulatory networks, revealing conserved and lineage-specific mechanisms.

ATP-independent unfolding of ubiquitin by Ufd1 initiates Cdc48/p97-mediated substrate processing

The paper shows Ufd1's UT3 domain unfolds ubiquitin in an ATP-independent manner, enabling Cdc48/p97 to process polyubiquitinated substrates.

A novel mechanism of ubiquitin-charging a bivalent E2:RING E3 complex

This study identifies a novel mechanism by which a bivalent E2:RING E3 complex facilitates E2 charging through competitive inhibition and accelerated release of charged E2.

Ubiquitin Chloromethylketone Probe Enables Activity-based, Selective Protein Profiling of E2 Ubiquitin Conjugating Enzymes

This paper introduces UbCMK, a probe that selectively profiles E2 ubiquitin conjugating enzymes and DUBs, revealing their activity under various stress conditions.

Trans-branching of polyubiquitin chains orchestrates the DNA replication stress response

The paper shows that branching of polyubiquitin chains on PCNA, mediated by UBE2K, orchestrates the DNA replication stress response by promoting re-priming of stalled forks and requiring BRCA1-dependent repair.

ZNF217-USP15 signaling loop regulates oncogenic phenotypes in ovarian cancer cells

This study identifies USP15 as a regulator of ZNF217 stability, revealing a feedback loop that promotes ovarian cancer progression and therapeutic resistance.