Task: Question Generation
Input (English): Polyglutamine diseases, including Huntington's disease, designate a group of nine neurodegenerative disorders characterized by the presence of a toxic polyglutamine expansion in specific target proteins. Using cell and mouse models, we have shown that expanded polyglutamine led to activation of the stress kinase JNK and the transcription factor AP-1, which are implicated in neuronal death. Polyglutamine expansion-induced stress shared common features with protein-damaging stress such as heat shock, because activation of JNK involved inhibition of JNK phosphatase activities. Indeed, expanded polyglutamine impaired the solubility of the dual-specificity JNK phosphatase M3/6. Aggregation of M3/6 by polyglutamine expansion appeared to be indirect, because M3/6 was not recruited into polyglutamine inclusions. The heat shock protein HSP70, which is known to inhibit JNK during the heat shock response, suppressed polyglutamine-mediated aggregation of M3/6 and activation of JNK. Interestingly, levels of HSP70 were down-regulated by polyglutamine expansion. We suggest that reduction of HSP70 by expanded polyglutamine is implicated in aggregation and inhibition of M3/6 and in activation of JNK and AP-1.
Output (English): Which protein is affected by dusp8 activation?