The conserved Ser/Thr protein phosphatase 5 (PP5) is involved in the regulation of
key cellular processes, including DNA damage repair and cell division in eukaryotes.
As a co-chaperone of Hsp90, PP5 has been shown to modulate the maturation and activity
of numerous oncogenic kinases. Here, we identify a novel substrate of PP5, the Polo-like
kinase 4 (Plk4), which is the master regulator of centriole duplication in animal
cells. We show that PP5 specifically interacts with Plk4, and is able to dephosphorylate
the kinase in vitro and in vivo, which affects the interaction of Plk4 with its partner
proteins. In addition, we provide evidence that PP5 and Plk4 co-localize to the centrosomes
in Drosophila embryos and cultured cells. We demonstrate that PP5 is not essential;
the null mutant flies are viable without a severe mitotic phenotype; however, its
loss significantly reduces the fertility of the animals. Our results suggest that
PP5 is a novel regulator of the Plk4 kinase in Drosophila.
