Author: ["Yan-Fei Gao","Teng Li","Yan Chang","Yu-Bo Wang","Wei-Na Zhang","Wei-Hua Li","Kun He","Rui Mu","Cheng Zhen","Jiang-Hong Man","Xin Pan","Tao Li","Liang Chen","Ming Yu","Bing Liang","Yuan Chen","Qing Xia","Tao Zhou","Wei-Li Gong","Ai-Ling Li","Hui-Yan Li","Xue-Min Zhang"]
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Abstract
Aneuploidy and chromosomal instability are major characteristics of human cancer. These abnormalities can result from defects in the spindle assembly checkpoint (SAC), which is a surveillance mechanism for accurate chromosome segregation through restraint of the activity of the anaphase-promoting complex/cyclosome (APC/C). Here, we show that a CUE-domain-containing protein, CUEDC2, is a cell-cycle regulator that promotes spindle checkpoint inactivation and releases APC/C from checkpoint inhibition. CUEDC2 is phosphorylated by Cdk1 during mitosis. Depletion of CUEDC2 causes a checkpoint-dependent delay of the metaphase–anaphase transition. Phosphorylated CUEDC2 binds to Cdc20, an activator of APC/C, and promotes the release of Mad2 from APC/C–Cdc20 and subsequent APC/C activation. CUEDC2 overexpression causes earlier activation of APC/C, leading to chromosome missegregation and aneuploidy. Interestingly, CUEDC2 is highly expressed in many types of tumours. These results suggest that CUEDC2 is a key regulator of mitosis progression, and that CUEDC2 dysregulation might contribute to tumour development by causing chromosomal instability. The ubiquitin ligase APC/C is required for the metaphase-to-anaphase transition in mitosis. Downstream of Cdk1, CUEDC2 is shown to activate the APC/C by mediating the release of the checkpoint protein Mad2 from APC/C.Cite this article
Gao, YF., Li, T., Chang, Y. et al. Cdk1-phosphorylated CUEDC2 promotes spindle checkpoint inactivation and chromosomal instability. Nat Cell Biol 13, 924–933 (2011). https://doi.org/10.1038/ncb2287 