Cdc6 negatively modulates the microtubule organizing activity of the centrosome

Abstract

The centrosome serves as a major microtubule-organizing center (MTOC). The Cdc6 protein, which is a component of pre-replicative complex and a licensing factor for the initiation of chromosome replication, localizes to centrosomes during the S- and G2-phases of the cell cycle of human cells. We found that Cdc6 negatively regulates MTOC activity and the amounts of the integral proteins composing the pericentriolar material (PCM). Whereas Cdc6 depletion increased microtubule nucleation at the centrosomes, induction of Cdc6 in Cdc6-depleted cells reduced this increase. This increase and reduction correlated with the centrosomal intensities of PCM proteins, such as γ-tubulin, pericentrin, CDK5RAP2, and Cep192. These regulations required the ATPase activity as well as the centrosomal localization of Cdc6. These results suggest a novel Cdc6 function that regulates centrosome assembly and function.