Brownlee et al. describe how a phosphatase's regulatory subunit promotes centriole duplication and how a viral oncoprotein may mimic this activity to induce tumorigenesis.
The kinase Plk4 initiates the duplication of centrioles—the barrel-shaped structures that form centrosomes—once per cell cycle. Because centriole overduplication can lead to multipolar spindles, which may cause genomic instability and tumorigenesis, Plk4’s activity is limited to mitosis; during the rest of the cell cycle, the kinase triggers its own degradation by phosphorylating itself to create a binding site for the E3 ubiquitin ligase SCFSlimb. Brownlee et al. found that Protein Phosphatase 2A (PP2A) counteracts this autophosphorylation during mitosis to stabilize Plk4 and induce centriole duplication.
Plk4 levels didn't peak in mitosis if PP2A was inhibited, and Drosophila cells lacking the PP2A catalytic subunit or its regulatory partner Twins had fewer centrioles. Normal centriole numbers were restored if Plk4 was stabilized by the simultaneous depletion of SCFSlimb, however. Twins overexpression, on the other hand, stabilized Plk4 throughout the cell cycle, leading to centriole amplification.
The oncogenic SV40 virus small t-antigen (ST) also promotes centriole amplification, even though it is thought to inhibit PP2A by binding to the phosphatase and displacing its regulatory subunits. Brownlee et al. found that ST boosted Plk4 levels and restored centriole duplication to cells lacking Twins, suggesting that ST actually mimics Twins’ function rather than inhibiting PP2A activity at centrioles. ST, and perhaps other viral oncoproteins, may therefore induce tumorigenesis by keeping Plk4 elevated throughout the cell cycle.