title: Spatiotemporal dynamics of Aurora B-PLK1-MCAK signaling axis orchestrates kinetochore bi-orientation and faithful chromosome segregation.
abstract: Chromosome segregation in mitosis is orchestrated by the dynamic interactions between the kinetochore and spindle microtubules. The microtubule depolymerase mitotic centromere-associated kinesin (MCAK) is a key regulator for an accurate kinetochore-microtubule attachment. However, the regulatory mechanism underlying precise MCAK depolymerase activity control during mitosis remains elusive. Here, we describe a novel pathway involving an Aurora B-PLK1 axis for regulation of MCAK activity in mitosis. Aurora B phosphorylates PLK1 on Thr210 to activate its kinase activity at the kinetochores during mitosis. Aurora B-orchestrated PLK1 kinase activity was examined in real-time mitosis using a fluorescence resonance energy transfer-based reporter and quantitative analysis of native PLK1 substrate phosphorylation. Active PLK1, in turn, phosphorylates MCAK at Ser715 which promotes its microtubule depolymerase activity essential for faithful chromosome segregation. Importantly, inhibition of PLK1 kinase activity or expression of a non-phosphorylatable MCAK mutant prevents correct kinetochore-microtubule attachment, resulting in abnormal anaphase with chromosome bridges. We reason that the Aurora B-PLK1 signaling at the kinetochore orchestrates MCAK activity, which is essential for timely correction of aberrant kinetochore attachment to ensure accurate chromosome segregation during mitosis.
authors.affiliation: Anhui Key Laboratory of Cellular Dynamics and Chemical Biology, University of Science &Technology of China, Hefei 230027, China.
authors.forename: Hengyi
authors.initials: H
authors.lastname: Shao
authors.affiliation: 1] Anhui-MSM Joint Research Group for Cellular Dynamics, Hefei National Laboratory for Physical Sciences at Nanoscale, Hefei 230027, China [2] Department of Physiology, Morehouse School of Medicine, Atlanta, GA 30310, USA.
authors.forename: Yuejia
authors.initials: Y
authors.lastname: Huang
authors.affiliation: 1] Anhui Key Laboratory of Cellular Dynamics and Chemical Biology, University of Science &Technology of China, Hefei 230027, China [2] Department of Physiology, Morehouse School of Medicine, Atlanta, GA 30310, USA.
authors.forename: Liangyu
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Anhui Key Laboratory of Cellular Dynamics and Chemical Biology, University of Science &Technology of China, Hefei 230027, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Yuan
authors.affiliation: 1] Anhui Key Laboratory of Cellular Dynamics and Chemical Biology, University of Science &Technology of China, Hefei 230027, China [2] Department of Physiology, Morehouse School of Medicine, Atlanta, GA 30310, USA.
authors.forename: Youjun
authors.initials: Y
authors.lastname: Chu
authors.affiliation: 1] Anhui Key Laboratory of Cellular Dynamics and Chemical Biology, University of Science &Technology of China, Hefei 230027, China [2] Anhui-MSM Joint Research Group for Cellular Dynamics, Hefei National Laboratory for Physical Sciences at Nanoscale, Hefei 230027, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Dou
authors.affiliation: Anhui Key Laboratory of Cellular Dynamics and Chemical Biology, University of Science &Technology of China, Hefei 230027, China.
authors.forename: Changjiang
authors.initials: C
authors.lastname: Jin
authors.affiliation: Department of Physiology, Morehouse School of Medicine, Atlanta, GA 30310, USA.
authors.forename: Minerva
authors.initials: M
authors.lastname: Garcia-Barrio
authors.affiliation: 1] Anhui Key Laboratory of Cellular Dynamics and Chemical Biology, University of Science &Technology of China, Hefei 230027, China [2] Anhui-MSM Joint Research Group for Cellular Dynamics, Hefei National Laboratory for Physical Sciences at Nanoscale, Hefei 230027, China [3] Department of Physiology, Morehouse School of Medicine, Atlanta, GA 30310, USA.
authors.forename: Xing
authors.initials: X
authors.lastname: Liu
authors.affiliation: Anhui Key Laboratory of Cellular Dynamics and Chemical Biology, University of Science &Technology of China, Hefei 230027, China.
authors.forename: Xuebiao
authors.initials: X
authors.lastname: Yao
mesh_terms: D064107:Aurora Kinase B / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D020090:Chromosome Segregation / Q000502:physiology*; D002877:Chromosomes, Human / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D018386:Kinetochores / Q000378:metabolism*; D008938:Mitosis / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D000097869:Polo-Like Kinase 1
chemical_list: D064107:Aurora Kinase B; D018797:Cell Cycle Proteins; D016547:Kinesins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D000097869:Polo-Like Kinase 1; C091489:KIF2C protein, human; C576921:AURKB protein, human