PLK4 homodimerization is required for CEP152 centrosome localization and spindle organization

Polo-Like Kinase 4 (PLK4) is a unique serine/threonine kinase family member that homodimerizes using its cryptic polo-box (CPB) region. Homodimerization of PLK4 causes transphosphorylation, which activates its ubiquitin-mediated degradation. Interestingly, CPB is also involved in interaction with the upstream centrosome recruiters, CEP152 and CEP192 in human cells. However, the effect of PLK4 homodimerization on the CEP192-CEP152 network remains unexplored. In this work, we identified a frequently occurring cancerous PLK4 variant (E774*), which truncated the protein at the 774 position. The truncated PLK4 is unable to homodimerize and interact with CEP152 and CEP192. During the S-phase progression, we show that CEP152 recruits PLK4 to centrosomes. The homodimerization of PLK4, in turn, is needed for maintaining CEP152 centrosome levels. CEP152 levels correlate to pericentrin at S-phase centrosomes, which generate focused spindles by the M-phase. The homodimerization mutant exhibits reduced levels of CEP152 and pericentrin at S-phase centrosomes, which causes unfocused spindles at the M-phase and reduces cell viability. This work shows the requirement of PLK4 homodimerization for proper centrosome and spindle organization, which is disrupted in cancer.