Study unravels novel centromeric functional protein

Scientists have discovered a new centromeric functional protein and dubbed it Adaptor of polo1 (Apolo1). The findings of the study were reported in Cell Reports.

This breakthrough was achieved by a team of researchers headed by Prof. Xuebiao Yao, Xing Liu, and Dan Liu from the University of Science and Technology of China of the Chinese Academy of Sciences.

Apart from being crucial for the life history of humans, accurate self-replication of cells is also a major assurance of human health. When mitosis occurs, the paternal genetic information included in chromosomes is transmitted equally to two daughter cells following several complex movements.

PLK1 is one of the crucial regulatory kinases in mitosis and is responsible for the mitotic entry, maturation of centrosomes, spindle plasticity, arrangement of the chromosomes, and cytokinesis. But the in-depth molecular mechanism of PLK1 kinase activity regulation in the prophase and metaphase of mitosis has remained unclear.

The researchers involved in this study found a new centromeric functional protein by making use of a eukaryotic mitotic regulatory network gene coevolution approach and organelle spatiotemporal proteomics method. They named the protein Apolo1.

When it comes to molecular mechanism, Apolo1 interacts with the polo-box domain (PBD) domain of PLK1 using its N-terminal. Meanwhile, its C-terminal includes a classical PP1γ Phosphatase binding motif. A fascinating fact is that the binding activity of Apolo 1’s PP1γ is controlled by the phosphorylation of PLK1 kinase.

Thus, PLK1-Apolo1-PP1γ builds a new functional feedback loop to accurately control mitotic chromosome dynamics and centromere plasticity in the prophase and metaphase of mitosis to guarantee the stability of the genome.

The model biology and functional proteomics studies indicated that Apolo1 has a crucial role in maintaining stem cell proliferation and genomic stability.

This study systematically investigated the biochemical function of Apolo1 and demonstrated how Apolo1 dynamically connected centromeric protein kinase PLK1 with phosphatase PP1γ. It offers a basis for in-depth structure-activity studies in the future.

Source:
Journal reference:

Xu, L., et al. (2021) Feedback control of PLK1 by Apolo1 ensures accurate chromosome segregation. Cell Reports. doi.org/10.1016/j.celrep.2021.109343.

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