Cyclin-dependent kinase-1 (Cdk1)/cyclin B1 dictates cell fate after mitotic arrest via phosphoregulation of antiapoptotic Bcl-2 proteins.

摘要: The prevailing model suggests that cell fate after mitotic arrest depends on two independent and competing networks control cyclin B1 degradation the generation of death signals. However, recent evidence for Cdk1/cyclin B1-mediated phosphorylation inactivation antiapoptotic Bcl-2 proteins existence significant cross-talk interdependence between these pathways. Further, nature signals has remained elusive. In this study, we sought to test hypothesis is dictated by robustness signaling identify may represent a signature. We show when treated with Taxol, slippage-resistant HT29 colon carcinoma cells display robust Cdk1 activity extensive Mcl-1/Bcl-xL die in mitosis, whereas slippage-prone DLD-1 weak partial transient subsequent interphase or survive. Furthermore, modulation axis, either inhibition enforcing cells, evokes switch fate, indicating strength key determinant outcome. These findings provide novel insight into pathways regulate death, suggest events be useful as marker define susceptibility antimitotic drugs, encourage revision current describing arrest.