Ataxin‐3 is a deubiquitinase and polyglutamine disease protein whose cellular properties and functions are not entirely understood. Mutations in ataxin‐3 cause spinocerebellar ataxia type 3 (SCA3), a neurodegenerative disorder that is a member of the polyglutamine family of diseases. Two major isoforms arise from alternative splicing of ATXN3 and are differently toxic in vivo as a result of faster proteasomal degradation of one isoform compared to the other. The isoforms vary only at their C‐termini, suggesting that the hydrophobic C‐terminus of the more quickly degraded form of ataxin‐3 (here referred to as isoform 2) functions as a degron—that is, a peptide sequence that expedites the degradation of its host protein. We explored this notion in this study and present evidence that: (a) the C‐terminus of ataxin‐3 isoform 2 signals its degradation in a proteasome‐dependent manner, (b) this effect from the C‐terminus of isoform 2 does not require the ubiquitination of ataxin‐3, and (c) the isolated C‐terminus of isoform 2 can enhance the degradation of an unrelated protein. According to our data, the C‐terminus of ataxin‐3 isoform 2 is a degron, increasing overall understanding of the cellular properties of the SCA3 protein.

中文翻译：

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聚谷氨酰胺疾病蛋白 ataxin-3 疏水 C 端的降解能力。

Ataxin-3 是一种去泛素化酶和多聚谷氨酰胺疾病蛋白，其细胞特性和功能尚不完全清楚。ataxin-3 的突变会导致脊髓小脑性共济失调 3 (SCA3)，这是一种神经退行性疾病，属于多聚谷氨酰胺家族疾病。两种主要的异构体来自ATXN3 的选择性剪接，并且在体内具有不同的毒性由于与另一种异构体相比，一种异构体的蛋白酶体降解速度更快。异构体仅在其 C 端变化，这表明更快速降解形式的 ataxin-3（此处称为异构体 2）的疏水性 C 端起降解作用，即加速降解的肽序列其宿主蛋白质。我们在本研究中探讨了这一概念，并提供了以下证据：（a）ataxin-3 异构体 2 的 C 端以蛋白酶体依赖性方式发出其降解信号，（b）异构体 2 的 C 端的这种效应不会需要 ataxin-3 的泛素化，并且 (c) 异构体 2 的分离 C 端可以增强无关蛋白质的降解。根据我们的数据，ataxin-3 异构体 2 的 C 端是一个 degron，