Reactive oxygen species-dependent down-regulation of ubiquitin C-terminal hydrolase in Schizosaccharomyces pombe

Abstract

The Schizosaccharomyces pombe sdu1 + gene, belonging to the PPPDE superfamily of deubiquitinating enzyme (DUB) genes, was previously shown to encode a protein with ubiquitin C-terminal hydrolase (UCH) activity and to participate in the response against oxidative and nitrosative stresses. This work focused on the reactive oxygen species (ROS)-dependent regulation of the S. pombe sdu1 + gene. UCH activities, encoded by the sdu1 + gene, were attenuated in the S. pombe cells exposed to H2O2, superoxide radical-generating menadione (MD), and nitric oxide (NO)-generating sodium nitroprusside (SNP). Reduced glutathione (GSH) and its precursor N-acetylcysteine (NAC) were able to significantly enhance the UCH activities in the absence or presence of H2O2. However, the influences of both GSH and NAC on the ROS levels in the absence or presence of H2O2 were opposite to their effects on the UCH activities under the same conditions. The UCH activities in the Sdu1-overexpressing S. pombe cells were also diminished under exposure to H2O2, MD and SNP, but still remained to be higher than those in the vector control cells. In brief, it is proposed that the S. pombe sdu1 + gene is regulated by ROS in a negative manner, the meaning of which largely remains elusive.