AI Article Synopsis
- Deubiquitinating enzymes (DUBs), like ataxin-3, are crucial for maintaining protein balance and play a role in neurodegenerative diseases, specifically spinocerebellar ataxia type 3 (SCA3).
- In SCA3, an expanded polyglutamine (polyQ) sequence in ataxin-3 causes protein aggregation, leading to neuronal issues.
- Mass spectrometry revealed that both normal and polyQ-expanded ataxin-3 interact with proteins involved in protein quality control and mitochondria, with certain mitochondrial proteins showing increased interactions in the expanded version, highlighting ataxin-3's importance in both ubiquitin and mitochondrial biology.
Article Abstract
Deubiquitinating enzymes (DUBs) play important roles in a variety of cellular processes, including regulation of protein homeostasis. The DUB ataxin-3 is an enzyme implicated in protein quality control mechanisms. In the neurodegenerative disease spinocerebellar ataxia type 3 (SCA3), ataxin-3 contains an expanded polyglutamine (polyQ) stretch that leads to aggregation of the protein and neuronal dysfunction. Increasing the understanding of ataxin-3 protein interaction partners could help to elucidate disease mechanisms. Hence, we analyzed the repertoire of proteins interacting with normal and polyQ expanded ataxin-3 by mass spectrometry. This showed that both normal and polyQ expanded ataxin-3 interacted with components of the protein quality control system and mitochondria. Five proteins showed increased interaction with polyQ expanded ataxin-3 relative to normal and three of these were mitochondrial proteins. The analyses underline the role of ataxin-3 in ubiquitin biology and point towards a role in mitochondrial biology.
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| http://dx.doi.org/10.1016/j.neuint.2017.10.013 | DOI Listing |
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