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Mutant ubiquitin (UBB +1 ) associated with neurodegenerative disorders is hydrolyzed by ubiquitin C‐terminal hydrolase L3 (UCH‐L3)
Author(s) -
Dennissen Frank J.A.,
Kholod Natalia,
Hermes Denise J.H.P.,
Kemmerling Nadja,
Steinbusch Harry W.M.,
Dantuma Nico P.,
van Leeuwen Fred W.
Publication year - 2011
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2011.06.037
Subject(s) - deubiquitinating enzyme , ubiquitin , mutant , chemistry , hydrolase , enzyme , microbiology and biotechnology , biochemistry , biology , gene
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 (UB G76Y ) 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.