Dysfunction of protein quality control contributes to the cellular pathology of polyglutamine (polyQ) expansion diseases and other neurodegenerative disorders associated with aggregate deposition. Here we analyzed how polyQ aggregation interferes with the clearance of misfolded proteins by the ubiquitin-proteasome system (UPS). We show in a yeast model that polyQ-expanded proteins inhibit the UPS-mediated degradation of misfolded cytosolic carboxypeptidase Y(∗) fused to green fluorescent protein (GFP) (CG(∗)) without blocking ubiquitylation or proteasome function. Quantitative proteomic analysis reveals that the polyQ aggregates sequester the low-abundant and essential Hsp40 chaperone Sis1p. Overexpression of Sis1p restores CG(∗) degradation. Surprisingly, we find that Sis1p, and its homolog DnaJB1 in mammalian cells, mediates the delivery of misfolded proteins into the nucleus for proteasomal degradation. Sis1p shuttles between cytosol and nucleus, and its cellular level limits the capacity of this quality control pathway. Upon depletion of Sis1p by polyQ aggregation, misfolded proteins are barred from entering the nucleus and form cytoplasmic inclusions.

The sol–gel nanoporous capturing technology represents a powerful approach where the sol–gel matrix constrains the motion of the encapsulated biomolecules (proteins, peptides, chemicals, antibodies, nucleotides, etc.) without physical adsorption or any modifications. This technology can be applied to multiplex immunoassay platform because several disease markers can be immobilized and tested at once. In this study, we have tested several thousand specimens using Hi3‐1 Multiplex human immunodeficiency virus (HIV) 1/2 and hepatitis C virus (HCV) antibody detection kit at two clinical trials institutes. These results showed a highest sensitivity (100%, n = 500 HIV‐positive specimens and n = 400 HCV‐positive) and specificity (99.99% for HIV and 99.83% for HCV, n = 7706 negative specimens) by using Hi3‐1 kit, which screens HIV1/2 and HCV antibodies simultaneously. Finally, we suggested that our screening technology was successfully utilized as a multiplex HIV and HCV diagnostic tool for blood bank screening.