leupeptins and 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin

leupeptins has been researched along with 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin* in 1 studies

Other Studies

1 other study(ies) available for leupeptins and 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin

ArticleYear
Chaperone-mediated 26S proteasome remodeling facilitates free K63 ubiquitin chain production and aggresome clearance.
    The Journal of biological chemistry, 2015, Apr-10, Volume: 290, Issue:15

    Efficient elimination of misfolded proteins by the proteasome system is critical for proteostasis. Inadequate proteasome capacity can lead to aberrant aggregation of misfolded proteins and inclusion body formation, a hallmark of neurodegenerative disease. The proteasome system cannot degrade aggregated proteins; however, it stimulates autophagy-dependent aggregate clearance by producing unanchored lysine (K)63-linked ubiquitin chains via the proteasomal deubiquitinating enzyme Poh1. The canonical function of Poh1, which removes ubiquitin chains en bloc from proteasomal substrates prior to their degradation, requires intact 26S proteasomes. Here we present evidence that during aggresome clearance, 20S proteasomes dissociate from protein aggregates, while Poh1 and selective subunits of 19S proteasomes are retained. The dissociation of 20S proteasome components requires the molecular chaperone Hsp90. Hsp90 inhibition suppresses 26S proteasome remodeling, unanchored ubiquitin chain production, and aggresome clearance. Our results suggest that 26S proteasomes undergo active remodeling to generate a Poh1-dependent K63-deubiquitinating enzyme to facilitate protein aggregate clearance.

    Topics: Benzoquinones; Blotting, Western; Cell Line, Tumor; Cysteine Proteinase Inhibitors; Histone Deacetylase 6; Histone Deacetylases; HSP90 Heat-Shock Proteins; Humans; Lactams, Macrocyclic; Leupeptins; Lysine; Microscopy, Confocal; Proteasome Endopeptidase Complex; Protein Aggregates; RNA Interference; Trans-Activators; Ubiquitin; Ubiquitination

2015
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