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

Autor:	Dennissen, Frank J.A., Kholod, Natalia, Hermes, Denise J.H.P., Kemmerling, Nadja, Steinbusch, Harry W.M., Dantuma, Nico P., van Leeuwen, Fred W.
Předmět:	UBIQUITIN GENETIC mutation NEURODEGENERATION HYDROLYSIS HYDROLASES ALZHEIMER'S disease SACCHAROMYCES cerevisiae
Zdroj:	FEBS Letters; Aug2011, Vol. 585 Issue 16, p2568-2574, 7p
Abstrakt:	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. [Copyright &y& Elsevier]
Databáze:	Complementary Index
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