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• W2295819104 abstract "Abstract Proper cell-cycle progression requires tight temporal control of the Anaphase Promoting Complex/Cyclosome (APC/C), a large ubiquitin ligase that is activated by one of two co-activators, Cdh1 or Cdc20. APC/C and Cdc20 are already present during interphase but APC/C–Cdc20 regulation during this window of the cell cycle, if any, is unknown. Here we show that cyclin A2–Cdk2 binds and phosphorylates Cdc20 in interphase and this inhibits APC/C–Cdc20 activity. Preventing Cdc20 phosphorylation results in pre-mature activation of the APC/C–Cdc20 and several substrates, including cyclin B1 and A2, are destabilized which lengthens G2 and slows mitotic entry. Expressing non-degradable cyclin A2 but not cyclin B1 restores mitotic entry in these cells. We have thus uncovered a novel positive feedback loop centred on cyclin A2–Cdk2 inhibition of interphase APC/C–Cdc20 to allow further cyclin A2 accumulation and mitotic entry." @default.
• W2295819104 created "2016-06-24" @default.
• W2295819104 creator A5025805311 @default.
• W2295819104 creator A5030192348 @default.
• W2295819104 date "2016-03-10" @default.
• W2295819104 modified "2023-10-10" @default.
• W2295819104 title "Interphase APC/C–Cdc20 inhibition by cyclin A2–Cdk2 ensures efficient mitotic entry" @default.
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• W2295819104 doi "https://doi.org/10.1038/ncomms10975" @default.
• W2295819104 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4792957" @default.
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