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SCF regulates G2-M progression through control of CCNL1 ubiquitination

EMBO Rep. 2022-10; 
Siobhan O'Brien, Susan Kelso, Zachary Steinhart, Stephen Orlicky, Monika Mis, Yunhye Kim, Sichun Lin, Frank Sicheri, Stephane Angers
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摘要

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 inh... More

关键词

CDK11, FBXW7, cell cycle, cyclin L1, mitosis