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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.

Pubmed ID: 19473992

Authors

  • Yang X
  • Li H
  • Zhou Z
  • Wang WH
  • Deng A
  • Andrisani O
  • Liu X

Journal

The Journal of biological chemistry

Publication Data

July 10, 2009

Associated Grants

  • Agency: NCI NIH HHS, Id: K01 CA114401

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