Chuang KH~Wang Y, 2016

Pubmed ID 27170182
Title Ubiquilin/Dsk2 promotes inclusion body formation and vacuole (lysosome)-mediated disposal of mutated huntingtin.
Authors Kun-Han Chuang, Fengshan Liang, Ryan Higgins, Yanchang Wang
Abstract Ubiquilin proteins contain a ubiquitin-like domain (UBL) and ubiquitin-associated domain(s) that interact with the proteasome and ubiquitinated substrates, respectively. Previous work established the link between ubiquilin mutations and neurodegenerative diseases, but the function of ubiquilin proteins remains elusive. Here we used a misfolded huntingtin exon I containing a 103-polyglutamine expansion (Htt103QP) as a model substrate for the functional study of ubiquilin proteins. We found that yeast ubiquilin mutant (dsk2Δ) is sensitive to Htt103QP overexpression and has a defect in the formation of Htt103QP inclusion bodies. Our evidence further suggests that the UBL domain of Dsk2 is critical for inclusion body formation. Of interest, Dsk2 is dispensable for Htt103QP degradation when Htt103QP is induced for a short time before noticeable inclusion body formation. However, when the inclusion body forms after a long Htt103QP induction, Dsk2 is required for efficient Htt103QP clearance, as well as for autophagy-dependent delivery of Htt103QP into vacuoles (lysosomes). Therefore our data indicate that Dsk2 facilitates vacuole-mediated clearance of misfolded proteins by promoting inclusion body formation. Of importance, the defect of inclusion body formation in dsk2 mutants can be rescued by human ubiquilin 1 or 2, suggesting functional conservation of ubiquilin proteins.
Citation Mol. Biol. Cell 2016; 27:2025-36


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Papers Phenotype Conditions Collection Tested mutants Data Details
Chuang KH~Wang Y, 2016 growth (spot assay) expression of mutant huntingtin fragment [GAL] hap a ~4,800 None

Curation history


Nov. 14, 2016 Data to request.
May 4, 2017 Data requested.
May 8, 2017 Data not available.

Tested strains

Nov. 14, 2016 Tested strains to request.
May 4, 2017 Tested strains requested.
May 8, 2017 Tested strains not available.