Abstract
Mutant ubiquitin (UBB+1) accumulates in the hallmarks of tauopathies and polyglutamine diseases. We show that the deubiquitinating enzyme YUH1 of Saccharomyces cerevisiae and its mouse and human ortholog UCH-L3 are able to hydrolyze the C-terminal extension of UBB+1. This yields another dysfunctional ubiquitin molecule (UBG76Y) with biochemical properties similar to full length UBB+1. UBB+1 may be detected in post-mortem tissue due to impaired C-terminal truncation of UBB+1. Although the level of UCH-L3 protein in several neurodegenerative diseases is unchanged, we show that in vitro oxidation of recombinant UCH-L3 impairs its deubiquitinating activity. We postulate that impaired UCH-L3 function may contribute to the accumulation of full length UBB+1 in various pathologies. Crown Published by Elsevier B. V. on behalf of Federation of European Biochemical society. All rights reserved.
Original language | English |
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Pages (from-to) | 2568-2574 |
Journal | Febs Letters |
Volume | 585 |
Issue number | 16 |
DOIs | |
Publication status | Published - 19 Aug 2011 |
Keywords
- UBB+1
- Ubiquitin C-terminal hydrolase L3
- Yeast ubiquitin hydrolase 1
- Alzheimer's disease