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WWP2 is an E3 ubiquitin ligase for PTEN
Open accessAbstract
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.
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Metadata
- Authors
- Maddika, S., Kavela, S., Rani, N., Palicharla, V. R., Pokorny, J. L., Sarkaria, J. N., & Chen, J.
- Venue
- Nature Cell Biology
- Published
- 2011-05-01
- Volume
- 13
- Issue
- 6
- Pages
- 728-733
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- OpenAlex
- W2067576594
- Cited by
- 305
- References
- 41
- FWCI
- 7.88
- Type
- journal article
- Language
- en
- Open access
- green
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