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WWP2 is an E3 ubiquitin ligase for PTEN.


PTEN, a lipid phosphatase, is one of the most frequently mutated tumour suppressors in human cancer. Several recent studies have highlighted the importance of ubiquitylation in regulating PTEN tumour-suppressor function, but the enzymatic machinery required for PTEN ubiquitylation is not clear. In this study, by using a tandem affinity-purification approach, we have identified WWP2 (also known as atrophin-1-interacting protein 2, AIP-2) as a PTEN-interacting protein. WWP2 is an E3 ubiquitin ligase that belongs to the NEDD4-like protein family, which is involved in regulating transcription, embryonic stem-cell fate, cellular transport and T-cell activation processes. We show that WWP2 physically interacts with PTEN and mediates its degradation through a ubiquitylation-dependent pathway. Functionally, we show that WWP2 controls cellular apoptosis and is required for tumorigenicity of cells. Collectively, our results reveal a functional E3 ubiquitin ligase for PTEN that plays a vital role in tumour-cell survival.

Pubmed ID: 21532586


  • Maddika S
  • Kavela S
  • Rani N
  • Palicharla VR
  • Pokorny JL
  • Sarkaria JN
  • Chen J


Nature cell biology

Publication Data

June 2, 2011

Associated Grants

  • Agency: NCI NIH HHS, Id: CA016672
  • Agency: NCI NIH HHS, Id: CA108961
  • Agency: NCI NIH HHS, Id: P50 CA108961

Mesh Terms

  • Cell Line, Tumor
  • Humans
  • Male
  • Neoplasms
  • PTEN Phosphohydrolase
  • Signal Transduction
  • Ubiquitin-Protein Ligases