Author: ["Subbareddy Maddika","Sridhar Kavela","Neelam Rani","Vivek Reddy Palicharla","Jenny L. Pokorny","Jann N. Sarkaria","Junjie Chen"]
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Abstract
The lipid phosphatase and tumour suppressor PTEN is regulated by ubiquitylation. The E3 ligase WWP2/AIP-2 is found to mediate PTEN degradation and is suggested to function as an oncogene. 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.Cite this article
Maddika, S., Kavela, S., Rani, N. et al. WWP2 is an E3 ubiquitin ligase for PTEN. Nat Cell Biol 13, 728–733 (2011). https://doi.org/10.1038/ncb2240 