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FipoQ/FBXO33, a Cullin-1-based ubiquitin ligase complex component modulates ubiquitination and solubility of polyglutamine disease protein.

J Neurochem. 2019; 
Chen ZS,, Wong AKY,, Cheng TC,, Koon AC, Chan HYE,,,.
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摘要

Polyglutamine (polyQ) diseases describe a group of progressive neurodegenerative disorders caused by the CAG triplet repeat expansion in the coding region of the disease genes. To date, nine such diseases, including spinocerebellar ataxia type 3 (SCA3), have been reported. The formation of SDS-insoluble protein aggregates in neurons causes cellular dysfunctions, such as impairment of the ubiquitin-proteasome system, and contributes to polyQ pathologies. Recently, the E3 ubiquitin ligases, which govern substrate specificity of the ubiquitin-proteasome system, have been implicated in polyQ pathogenesis. The Cullin (Cul) proteins are major components of Cullin-RING ubiquitin ligases (CRLs) complexes that are evolu... More

关键词

Drosophila melanogaster ; F-box protein; protein solubility; spinocerebellar ataxia; ubiquitin-proteasome