摘要
During cell division,chromosome segregation is orchestrated by the interaction of spindle microtubules with the centromere.Accurate attachment of spindle microtubules to kinetochore requires the chromosomal passenger of Aurora B kinase complex with borealin,INCENP and survivin(SUR).The current working model argues that SUR is responsible for docking Aurora B to the centromere whereas its precise role in Aurora B activation has been unclear.Here,we show that Aurora B kinase activation requires SUR priming phosphorylation at Ser20 which is catalyzed by polo-like kinase 1(PLK1).Inhibition of PLK1 kinase activity or expression of non-phosphorylatable SUR mutant prevents Aurora B activation and correct spindle microtubule attachment.The PLK1-mediated regulation of Aurora B kinase activity was examined in real-time mitosis using fluorescence resonance energy transfer-based reporter and quantitative analysis of native Aurora B substrate phosphorylation.We reason that the PLK1-mediated priming phosphorylation is critical for orchestrating Aurora B activity in centromere which is essential for accurate chromosome segregation and faithful completion of cytokinesis.
基金
supported,in whole or in part,by National Institutes of Health(NIH)Grants DK-56292 and CA132389 and NIH,National Center for Research Resources(NCRR),Grant UL1 RR025008 from the Clinical and Translational Science Award Program
supported by Chinese Natural Science Foundation Grants 30500183 and 30870990(to X.D.),and 90508002 and 90913016(to X.Y.)
Chinese Academy of Science Grants KSCX1-YW-R-65,KSCX2-YW-H-10,KSCX2-YW-R-195
the Major State Basic Research Development Program of China(973 Program)2007CB914503 and 2010CB912103
International Collaboration Grant 2009DFA31010(to X.D.)and Technology Grant 2006BAI08B01-07(to X.D.)
a Georgia Cancer Coalition Breast Cancer Research Grant
Atlanta Clinical and Translational Science Award Chemical Biology Grant P20RR011104 and Anhui Province Key Project Grant,08040102005
supported in part by NCRR,NIH,Grant G12RR03034.