Plk1-mediated phosphorylation of Topors regulates p53 stability

Polo-like kinase 1 (PLK1) overexpression is associated with tumorigenesis by an unknown mechanism. Likewise, PLK1 was suggested to act as a negative regulator of tumor suppressor p53, but the mechanism remains to be determined. Herein, we have identified Topoisomerase I-binding protein (Topors), a p53-binding protein, as a PLK1 target. We show that PLK1 phosphorylates Topors on Ser(718) in vivo. Significantly, expression of a Plk1-unphosphorylatable Topors mutant (S718A) leads to a dramatic accumulation of p53 through inhibition of p53 degradation. Topors is an ubiquitin and small ubiquitin-like modifier ubiquitin-protein isopeptide Ligase (SUMO E3) Ligase. Plk1-mediated phosphorylation of Topors inhibits Topors-mediated sumoylation of p53, whereas p53 ubiquitination is enhanced, leading to p53 degradation. These results demonstrate that PLK1 modulates Topors activity in suppressing p53 function and identify a likely mechanism for the tumorigenic potential of PLK1.