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• W3036585809 endingPage "1519" @default.
• W3036585809 startingPage "1519" @default.
• W3036585809 abstract "Ubiquitination is a post-translational modification that regulates cellular processes by altering the interactions of proteins to which ubiquitin, a small protein adduct, is conjugated. Ubiquitination yields various products, including mono- and poly-ubiquitinated substrates, as well as unanchored poly-ubiquitin chains whose accumulation is considered toxic. We previously showed that transgenic, unanchored poly-ubiquitin is not problematic in Drosophila melanogaster. In the fruit fly, free chains exist in various lengths and topologies and are degraded by the proteasome; they are also conjugated onto other proteins as one unit, eliminating them from the free ubiquitin chain pool. Here, to further explore the notion of unanchored chain toxicity, we examined when free poly-ubiquitin might become problematic. We found that unanchored chains can be highly toxic if they resemble linear poly-ubiquitin that cannot be modified into other topologies. These species upregulate NF-κB signaling, and modulation of the levels of NF-κB components reduces toxicity. In additional studies, we show that toxicity from untethered, linear chains is regulated by isoleucine 44, which anchors a key interaction site for ubiquitin. We conclude that free ubiquitin chains can be toxic, but only in uncommon circumstances, such as when the ability of cells to modify and regulate them is markedly restricted." @default.
• W3036585809 created "2020-06-25" @default.
• W3036585809 creator A5015630273 @default.
• W3036585809 creator A5015909717 @default.
• W3036585809 creator A5072852131 @default.
• W3036585809 creator A5086545751 @default.
• W3036585809 date "2020-06-22" @default.
• W3036585809 modified "2023-09-23" @default.
• W3036585809 title "Isoleucine 44 Hydrophobic Patch Controls Toxicity of Unanchored, Linear Ubiquitin Chains through NF-κB Signaling" @default.
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• W3036585809 doi "https://doi.org/10.3390/cells9061519" @default.
• W3036585809 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7348737" @default.
• W3036585809 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/32580388" @default.
• W3036585809 hasPublicationYear "2020" @default.
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