Quantitative proteomics in a cellular model of human ATXN1(Q82) protein aggregation

Spinocerebellar ataxia type-1 is caused by an abnormally expanded polyglutamine (polyQ) tract in ataxin-1 protein. These expansions are responsible for protein misfolding and self-assembly into intranuclear inclusion bodies (IIBs) that are linked to neuronal death. Here, we describe a nuclear protein aggregation model of pathogenic human ataxin-1. Using an inducible Sleeping Beauty transposon system, we overexpressed ATXN1(Q82) in human mesenchymal stem cells that are resistant to the early cytotoxic effects of the mutant protein. We characterized the proteome of cells containing insoluble polyQ IIBs which gradually occupy the nuclei. In response to their formation, our proteomics analysis reveals a perturbed protein interaction network affecting critical cellular processes and indicates major kinases which may affect polyQ protein aggregation.