The spindle assembly checkpoint and spatial activation of Polo kinase determine the duration of cell division and prevent tumor formation.

Stem cells exist in limited numbers in tissues and ensure their development and repair. To do this, stem cells ensure a rigorous progression of mitotic events. This progression is essential to avoid chromosomal segregation errors during cell division and the formation of aneuploid daughter cells with impaired proliferative capacities. Furthermore, during mitosis, these stem cells are characterized by their polarization along an apical-basal axis, which results in the differential distribution of identity determinants at the stem cell cortex. The orientation of the mitotic spindle along this axis allows the asymmetric distribution and regulates the differential fate of future daughter cells. This differential segregation is necessary to generate healthy tissue and avoid tumor formation. The characterization of the molecules that regulate the coupling between mitotic progression and cell polarization is therefore a fundamental question.

Our team has shown that the activity levels of the Polo kinase regulate the duration of cell division. Polo activation is regulated via direct activating phosphorylation by Aurora A (at the mitotic spindle poles) and Aurora B (at the centromeres) kinases. Moreover, activation of Polo kinase by Aurora A is essential to maintain mitotic stem cell polarization and therefore to prevent tumor formation.

Our results therefore show that a phosphorylation cascade leading to the activation of Polo kinase by Aurora family kinases provides a crucial role for the coupling between mitotic progression and cell identity acquisition.


23/05/2022