D. Finley

A strict requirement in proteasome substrates for spacing between ubiquitin tag and degradation initiation elements

The paper shows that the distance between ubiquitin tags and degradation initiation elements determines proteasome-mediated protein degradation efficiency.

Proteostasis and lysosomal repair deficits in transdifferentiated neurons of Alzheimer's disease

This study uses transdifferentiated neurons to show lysosomal deficits are an early event in aging and Alzheimer's disease, leading to proteotoxic deposits and cell death.

An mTOR-independent Macroautophagy Activator Ameliorates Tauopathy and Prionopathy Neurodegeneration Phenotypes

The paper identifies CCT020312, an mTOR-independent autophagy activator, which reduces tauopathy and prionopathy neurodegeneration phenotypes by enhancing autophagy flux and clearing protein aggregates.

Global proteome metastability response in isogenic animals to missense mutations and polyglutamine expansions in aging

This study examines how proteome conformational stability changes in aging C. elegans due to missense mutations and polyglutamine expansions, revealing age-dependent metastable protein networks.

Mechanistic insights into dynamic mutual regulation of USP14 and proteasome

This study reveals the dynamic regulation of USP14 and proteasome through cryo-EM structures and time-resolved analysis, identifying three regulatory checkpoints in proteasome function.

Allosteric control of Ubp6 and the proteasome via a bidirectional switch

This study identifies an allosteric switch that controls Ubp6 and the proteasome, showing their active states are mutually exclusive.

Global proteomics of Ubqln2-based murine models of ALS

The paper identifies proteomic changes in Ubqln2 mutant mice and finds that TRIM32, PEG10, and CXX1B are linked to UBQLN2 function and degradation.

A general in vitro assay to study enzymatic activities of the ubiquitin system

The paper introduces a FRET-based assay to measure ubiquitination kinetics in vitro, demonstrating its versatility and compatibility with various enzyme combinations.

N-terminal ubiquitination of amyloidogenic proteins triggers removal of their oligomers by the proteasome holoenzyme

The paper shows that N-terminal ubiquitination of amyloidogenic proteins by UBE2W alters their aggregation process, enabling proteasome targeting of soluble oligomers.

Filamentous aggregates are fragmented by the proteasome holoenzyme

This study shows the proteasome holoenzyme fragments amyloid fibrils into smaller, more toxic species, suggesting a novel degradation mechanism for filamentous aggregates.

Visualizing ATP-dependent substrate-processing dynamics of the human 26S proteasome at near-atomic resolution

The paper presents cryo-EM structures of the human 26S proteasome in seven conformational states during polyubiquitylated protein degradation, revealing dynamic substrate-proteasome interactions and ATP hydrolysis mechanisms.

Conformational landscape of the p28-bound human proteasome regulatory particle

The paper determines the cryo-EM structure of the human proteasome regulatory particle bound to p28, revealing its dynamic conformational landscape and role in proteasome assembly.