Study of subcellular localization and proteolysis of ataxin-3

Chiara Pozzi, Marco Valtorta, Gabriella Tedeschi, Elena Galbusera, Valentina Pastori, Alessandra Bigi, Simona Nonnis, Eleonora Grassi, Paola Fusi

Research output: Contribution to journalArticlepeer-review


In this work we investigate subcellular localization and proteolytic cleavage of different forms of ataxin-3 (AT-3), the protein responsible for spinocerebellar ataxia type 3. Normal (AT-3Q6 and AT-3Q26) and pathological (AT-3Q72) ataxins-3, as well as two truncated forms lacking poly-Q, were studied. Full-length proteins were also expressed as C14A mutants, in order to assess whether AT-3 autoproteolytic activity was involved in its fragmentation. We found that both normal and pathological proteins localized in the cytoplasm and in the nucleus, as expected, but also in the mitochondria. Microsequencing showed that all ataxins-3 underwent the same proteolytic cleavage, removing the first 27 aminoacids. Interestingly, while normal ataxins were further cleaved at a number of caspase sites, pathological AT-3 was proteolyzed to a much lesser extent. This may play a role in the pathogenesis, hampering degradation of aggregation-prone expanded AT-3. In addition, autolytic cleavage was apparently not involved in AT-3 proteolysis.

Original languageEnglish
Pages (from-to)190-200
Number of pages11
JournalNeurobiology of Disease
Issue number2
Publication statusPublished - May 2008


  • Ataxin-3
  • Poly-Q
  • Protein aggregation
  • Proteolysis
  • Spinocerebellar ataxia type 3

ASJC Scopus subject areas

  • Neurology


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