Feedback control of PLK1 by Apolo1 ensures accurate chromosome segregation
| Autor: | Wenxiu Duan, Hadiyah N. Green, Lingluo Chu, Mahboob Ali, Xing Liu, Dongmei Wang, Lin Li, Xiao Yuan, Leilei Xu, Jianlin Lu, Zhen Dou, Yushu Ge, Anthony A. Hyman, Hequan Duan, Binwen Sun, Fatima Garba, Xuebiao Yao, Dan Liu, Ina Poser, McKay Mullen, Ruijun Tian, Weijun Pan |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Cell division
QH301-705.5 Amino Acid Motifs Mitosis Cell Cycle Proteins Protein Serine-Threonine Kinases PLK1 Article General Biochemistry Genetics and Molecular Biology Chromosome segregation Phosphoserine Chromosome Segregation Proto-Oncogene Proteins Phosphoprotein Phosphatases Humans Amino Acid Sequence Biology (General) Phosphorylation Prometaphase Kinase activity PP1γ Kinetochores Feedback Physiological Kinetochore Chemistry Proteins kinetochore Cell biology Spindle checkpoint HEK293 Cells Apolo1 HeLa Cells Protein Binding |
| Zdroj: | Cell reports Cell Reports, Vol 36, Iss 2, Pp 109343-(2021) |
| ISSN: | 2211-1247 |
| Popis: | SUMMARY Stable transmission of genetic material during cell division requires accurate chromosome segregation. PLK1 dynamics at kinetochores control establishment of correct kinetochore-microtubule attachments and subsequent silencing of the spindle checkpoint. However, the regulatory mechanism responsible for PLK1 activity in prometaphase has not yet been affirmatively identified. Here we identify Apolo1, which tunes PLK1 activity for accurate kinetochore-microtubule attachments. Apolo1 localizes to kinetochores during early mitosis, and suppression of Apolo1 results in misaligned chromosomes. Using the fluorescence resonance energy transfer (FRET)-based PLK1 activity reporter, we found that Apolo1 sustains PLK1 kinase activity at kinetochores for accurate attachment during prometaphase. Apolo1 is a cognate substrate of PLK1, and the phosphorylation enables PP1γ to inactivate PLK1 by dephosphorylation. Mechanistically, Apolo1 constitutes a bridge between kinase and phosphatase, which governs PLK1 activity in prometaphase. These findings define a previously uncharacterized feedback loop by which Apolo1 provides fine-tuning for PLK1 to guide chromosome segregation in mitosis. Graphical abstract In brief Xu et al. identify Apolo1, which governs PLK1 activity and promotes faithful chromosome segregation in prometaphase by bridging kinase and phosphatase activities. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|