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• W4297370147 abstract "Abstract FBXW7 , which encodes a substrate specific receptor of an SCF E3 ligase complex, is a frequently mutated human tumor suppressor gene known to regulate the post-translational stability of various proteins involved in cellular proliferation. Here, using genome-wide CRISPR screens we report a novel synthetic lethal genetic interaction between FBXW7 and CCNL1 and describe CCNL1 as a new substrate of the SCF-FBXW7 E3 ligase. Further analysis showed that the CCNL1-CDK11 complex is critical at the G2-M phase of the cell cycle since defective CCNL1 accumulation, resulting from FBXW7 mutation, leads to shorter mitotic time. Cells harboring FBXW7 loss-of-function mutations are hypersensitive to treatment with a CDK11 inhibitor, highlighting a genetic vulnerability that could be leveraged for cancer treatment." @default.
• W4297370147 created "2022-09-28" @default.
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• W4297370147 date "2022-09-26" @default.
• W4297370147 modified "2023-10-06" @default.
• W4297370147 title "SCF^FBXW7 regulates G2-M progression through control of CCNL1 ubiquitination" @default.
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• W4297370147 doi "https://doi.org/10.1101/2022.09.26.509608" @default.
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