A cell cycle-dependent transition of acetylation to phosphorylation regulates timely centrosome maturation

Centrosomes must undergo maturation in the G2/M phases to activate the microtubule-organizing activity, ensuring proper bipolar spindle assembly and chromosome segregation. Polo-like kinase 1(PLK1) is crucial for centrosome maturation. How the cell cycle controls timely PLK1 recruitment and centrosome maturation remains elusive. Here, we find that the ubiquitin E3 ligase RNF40 localizes to centrosomes and is phosphorylated by CDK1 on T529/T557 in the G2/M phases. This phosphorylation primes its binding to PLK1 and promotes timely PLK1 recruitment and centrosome maturation, establishing the CDK1-RNF40-PLK1 cascade as a mechanism controlling centrosome maturation. We also find that RNF40 is acetylated in interphase and undergoes an acetylation-to-phosphorylation transition in late G2 and M phases, which permits timely activation of the CDK1-RNF40-PLK1 cascade. Constitutive RNF40 acetylation or deficient RNF40 phosphorylation impairs PLK1 localization, microtubule nucleation, and bipolar spindle assembly, causing mitotic catastrophe. Thus, the cell cycle-dependent transition of RNF40 modifications ensures timely centrosome maturation and chromosome segregation.