The polyglutamine protein ataxin-3 enables normal growth under heat shock conditions in the methylotrophic yeast Pichia pastoris.

摘要: The protein ataxin-3 carries a polyglutamine stretch close to the C-terminus that triggers neurodegenerative disease in humans when its length exceeds critical threshold. A role as transcriptional regulator but also ubiquitin hydrolase has been proposed for this protein. Here, we report that, expressed yeast Pichia pastoris, full-length enabled almost normal growth at 37 °C, well above physiological optimum of 30 °C. N-terminal Josephin domain (JD) was effective significantly less, whereas catalytically inactive JD completely ineffective. Based on MudPIT proteomic analysis, observed strain expressing full-length, functional displayed persistent upregulation enzymes involved mitochondrial energy metabolism during 37 °C compared with transformed empty vector. Concurrently, intracellular ATP levels were even higher than ones Elevated paralleled by both biosynthesis and biosynthetic pathways, several stress-induced proteins. similar pattern comparing another counterpart. We suggest such effects mostly result from mechanisms regulation.