Ubiquitin and proteasome pathways
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CLEO4-88 acts as a molecular glue with an EC50 of 12.5 nM to inhibit ACAA1 thiolase by inducing binding to GID4 in vitro and in cells.
- 1 cites
p97 is essential for late-stage thymocyte positive selection, with its loss causing a severe blockade in CD8+ lineage commitment and thymocyte development.
ABTB1 functions as an E3 ubiquitin ligase that suppresses Th17 cell differentiation by promoting STAT3 degradation, reducing autoimmune inflammation.
A novel Pseudomonas aeruginosa E3 ligase, PUL-1, was identified as a key regulator of virulence, revealing a unique mechanism of bacterial ubiquitin manipulation.
- Open access
HUWE1-HAPSTR1-USP7 complex amplifies ubiquitin chains on nuclear proteins, regulating stress-responsive degradation with a key role in neurodevelopmental disorders and cancer.
Kid (KIF22) forms a homodimer, moves processively along microtubules, and transports double-stranded DNA, challenging previous views of it as a monomeric, nonprocessive motor.
- Open access
Non-genetic amino acid substitutions significantly expand the human proteome, with 13,910 variants identified across 29 tissues, revealing a new layer of proteome diversity.
Novel CRBN molecular glues induce selective VAV1 degradation via a unique non-canonical RT-loop degron, with potency enhanced by conformational restriction strategies.
- Open access
- 4 cites
Loss of cGAS in killifish reduces age-related cellular senescence and transcriptional aging signatures but does not extend lifespan.
- Open access
A small-molecule bivalent glue activates cell death in diffuse large B cell lymphoma by linking lysine acetyltransferases to oncogenic pathways, achieving targeted epigenetic reprogramming.
- Open access
- 13 cites
CaSAP8 and CaDSK2a form a negative feedback loop that dynamically regulates thermotolerance in pepper, with CaSAP8 enhancing and CaDSK2a attenuating heat stress responses.
- Open access
- 1 cites
The fungal RIP hypermutator mechanism, targeting transposable elements, shares deep evolutionary roots across eukaryotes, highlighting conserved defense strategies.
- Open access
FAF1 and FAF2 significantly boost p97-UFD1-NPL4 complex activity, increasing substrate unfolding efficiency by engaging key cofactors and conserved activation motifs.
- Open access
TNG961 is a potent, selective oral degrader of HBS1L that effectively treats FOCAD-deleted cancers, including PRMT5 inhibitor-refractory models.
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