Department of Neuroscience, Faculty of Health Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands.
FEBS Lett. 2011 Aug 19;585(16):2568-74. doi: 10.1016/j.febslet.2011.06.037. Epub 2011 Jul 6.
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.
突变泛素 (UBB(+1)) 在神经tau 病变和多聚谷氨酰胺疾病的标志性特征中积累。我们表明，酿酒酵母的去泛素化酶 YUH1 及其小鼠和人类同源物 UCH-L3 能够水解 UBB(+1) 的 C 末端延伸。这产生了另一种具有类似于全长 UBB(+1) 的生化特性的功能失调的泛素分子 (UB(G76Y))。由于 UBB(+1) 的 C 末端截断受损，可能会在死后组织中检测到 UBB(+1)。尽管几种神经退行性疾病中 UCH-L3 蛋白的水平没有改变，但我们表明，重组 UCH-L3 的体外氧化会损害其去泛素化活性。我们假设，UCH-L3 功能受损可能导致各种病理中全长 UBB(+1) 的积累。
