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Plk1-mediated phosphorylation of Topors regulates p53 stability.

http://www.ncbi.nlm.nih.gov/pubmed/19473992

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.

Pubmed ID: 19473992 RIS Download

Mesh terms: Cell Cycle Proteins | Cell Line | Cell Line, Tumor | Gene Expression Regulation | Genes, p53 | Humans | Models, Biological | Mutation | Neoplasm Proteins | Nuclear Proteins | Phosphorylation | Protein Binding | Protein-Serine-Threonine Kinases | Proto-Oncogene Proteins | Tumor Suppressor Protein p53 | Ubiquitin-Protein Ligases

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Associated grants

  • Agency: NCI NIH HHS, Id: K01 CA114401

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