Chen ZS, Wong AKY, Cheng TC, Koon AC, Chan HYE. FipoQ/FBXO33, a Cullin-1 based ubiquitin ligase complex component modulates ubiquitination and solubility of polyglutamine disease protein. J Neurochem. 2019 Jan 26. doi: 10.1111/jnc.14669. PubMed PMID: 30685895.
From the abstract: "Polyglutamine (polyQ) diseases describe a group of progressive neurodegenerative disorders ... 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 (UPS), and contributes to polyQ pathologies. Recently, the E3 ubiquitin ligases, which govern substrate specificity of the UPS, have been implicated in polyQ pathogenesis. The Cullin (Cul) proteins are major components of Cullin-RING ubiquitin ligases (CRLs) complexes that are evolutionarily conserved in the Drosophila genome. In this study, we examined the effect of individual Culs on SCA3 pathogenesis ... We further performed a genetic modifier screen of the 19 Drosophila F-box genes, and identified F-box involved in polyQ pathogenesis (FipoQ) as a genetic modifier of SCA3 degeneration ... In the human SK-N-MC cell model, we identified F-box only protein 33 (FBXO33) exerts similar functions as FipoQ ... These findings will lead to a better understanding of the disease mechanism of SCA3, and provide insights on developing treatments against SCA3."
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