image: Apolo1 dynamically linked centromeric protein kinase PLK1 with phosphatase PP1 γ view more
Credit: XU Leilei et.al
The research team led by Prof. YAO Xuebiao, LIU Xing and LIU Dan from University of Science and Technology of China of the Chinese Academy of Sciences discovered a novel centromeric functional protein and named it Adaptor of polo1 (Apolo1). Results were published in Cell Reports.
Accurate self-replication of cells is not only an important part for their life history, but also a significant guarantee of human health. During the process of mitosis, the paternal genetic information contained in chromosomes is equally transmitted to two daughter cells after many complex movements.
PLK1 is one of the important regulatory kinases in mitosis, which takes charge for mitotic entry, centrosome maturation, spindle plasticity, chromosome arrangement and cytokinesis. However, the detailed molecular mechanism of PLK1 kinase activity regulation in the prophase and metaphase of mitosis is still unclear.
In this study, the researchers discovered a novel centromeric functional protein by adopting eukaryotic mitotic regulatory network gene coevolution strategy and organelle spatiotemporal proteomics method, and named it Apolo1.
In terms of molecular mechanism, Apolo1 interacts with polo-box domain (PBD) domain of PLK1 through its N-terminal, while its C-terminal contains a classical PP1γ Phosphatase binding motif. Interestingly, the binding activity of the PP1γ of Apollo 1 is regulated by the phosphorylation of PLK1 kinase. Therefore, PLK1-Apolo1-PP1γ constructs a new functional feedback loop to precisely regulate centromere plasticity and mitotic chromosome dynamics in the prophase and metaphase of mitosis to ensure the stability of genome.
The functional proteomics and model biology studies suggested that apolo1 plays an important role in maintaining genomic stability and stem cell proliferation.
This work systematically analyzed the biochemical function of apolo1, and revealed how Apolo1 dynamically linked centromeric protein kinase PLK1 with phosphatase PP1γ. It provides a basis for future detailed structure-activity studies.
Journal
Cell Reports
Article Title
Feedback control of PLK1 by Apolo1 ensures accurate chromosome segregation
Article Publication Date
12-Jul-2021