Mutant ubiquitin (UBB+1) associated with neurodegenerative disorders is hydrolyzed by ubiquitin C-terminal hydrolase L3 (UCH-L3)

Frank J. A. Dennissen, Natalia Kholod, Denise J. H. P. Hermes, Nadja Kemmerling, Harry W. M. Steinbusch, Nico P. Dantuma, Fred W. van Leeuwen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

31 Citations (Web of Science)


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 languageEnglish
Pages (from-to)2568-2574
JournalFebs Letters
Issue number16
Publication statusPublished - 19 Aug 2011


  • UBB+1
  • Ubiquitin C-terminal hydrolase L3
  • Yeast ubiquitin hydrolase 1
  • Alzheimer's disease

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