Spatiotemporal dynamics of Aurora B-PLK1-MCAK signaling axis orchestrates kinetochore bi-orientation and faithful chromosome segregation
| Autor: | Liangyu Zhang, Zhen Dou, Kai Yuan, Xuebiao Yao, Hengyi Shao, Minerva Garcia-Barrio, Xing Liu, Yuejia Huang, Youjun Chu, Changjiang Jin |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Aurora B kinase
Kinesins Mitosis Cell Cycle Proteins Biology Protein Serine-Threonine Kinases PLK1 Article Chromosome segregation 03 medical and health sciences 0302 clinical medicine Chromosome Segregation Proto-Oncogene Proteins Aurora Kinase B Chromosomes Human Humans Kinase activity Kinetochores 030304 developmental biology Anaphase 0303 health sciences Multidisciplinary Kinetochore Spindle apparatus Cell biology 030220 oncology & carcinogenesis HeLa Cells |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|