A dimer-monomer switch controls CHIP-dependent substrate ubiquitylation and processing.

The high substrate selectivity of the ubiquitin/proteasome system is mediated by a large group of E3 ubiquitin ligases. The ubiquitin ligase CHIP regulates the degradation of chaperone-controlled and chaperone-independent proteins. To understand how CHIP mediates substrate selection and processing, we performed a structure-function analysis of CHIP and addressed its physiological role in Caenorhabditis elegans and human cells.

Microplastics and Their Impact on Reproduction-Can we Learn From the Model?

Biologically active environmental pollutants have significant impact on ecosystems, wildlife, and human health. Microplastic (MP) and nanoplastic (NP) particles are pollutants that are present in the terrestrial and aquatic ecosystems at virtually every level of the food chain. Moreover, recently, airborne microplastic particles have been shown to reach and potentially damage respiratory systems.

Modelling the functional genomics of Parkinson's disease in Caenorhabditis elegans: LRRK2 and beyond.

For decades, Parkinson's disease (PD) cases have been genetically categorised into familial, when caused by mutations in single genes with a clear inheritance pattern in affected families, or idiopathic, in the absence of an evident monogenic determinant. Recently, genome-wide association studies (GWAS) have revealed how common genetic variability can explain up to 36% of PD heritability and that PD manifestation is often determined by multiple variants at different genetic loci. Thus, one of the current challenges in PD research stands in modelling the complex genetic architecture of this condition and translating this into functional studies.

The Machado-Joseph disease deubiquitylase ataxin-3 interacts with LC3C/GABARAP and promotes autophagy.

The pathology of spinocerebellar ataxia type 3, also known as Machado-Joseph disease, is triggered by aggregation of toxic ataxin-3 (ATXN3) variants containing expanded polyglutamine repeats. The physiological role of this deubiquitylase, however, remains largely unclear. Our recent work showed that ATX-3, the nematode orthologue of ATXN3, together with the ubiquitin-directed segregase CDC-48, regulates longevity in Caenorhabditis elegans.

Repair or destruction-an intimate liaison between ubiquitin ligases and molecular chaperones in proteostasis.

Cellular differentiation, developmental processes, and environmental factors challenge the integrity of the proteome in every eukaryotic cell. The maintenance of protein homeostasis, or proteostasis, involves folding and degradation of damaged proteins, and is essential for cellular function, organismal growth, and viability . Misfolded proteins that cannot be refolded by chaperone machineries are degraded by specialized proteolytic systems.