Site-specific phosphorylation of ZYG-1 regulates ZYG-1 stability and centrosome number

Abstract

Spindle bipolarity is critical for genomic integrity. As centrosome number often dictates bipolarity, tight control of centrosome assembly is vital for faithful cell division. The master centrosome regulator ZYG-1/Plk4 plays a pivotal role in this process. In C.elegans, casein kinase II (CK2) negatively regulates centrosome duplication by controlling centrosome-associated ZYG-1 levels. Here, we investigated CK2 as a regulator of ZYG-1 and its impact on centrosome assembly. We show that CK2 phosphorylates ZYG-1 invitro and physically interacts with ZYG-1 invivo. Depleting CK2 or blocking ZYG-1 phosphorylation at CK2 target sites leads to centrosome amplification. Non-phosphorylatable ZYG-1 mutants exhibit elevated ZYG-1 levels, leading to increased ZYG-1 and downstream factors at centrosomes, thus driving centrosome amplification. Moreover, inhibiting the 26S proteasome prevents degradation of the phospho-mimetic ZYG-1. Our findings suggest that CK2-dependent phosphorylation of ZYG-1 controls ZYG-1 levels via proteasomal degradation to limit centrosome number.