WWP2 is an E3 ubiquitin ligase for PTEN

Subbareddy Maddika, Sridhar Kavela, Neelam Rani, Vivek Reddy Palicharla, Jenny L. Pokorny, Jann N. Sarkaria, Junjie Chen

Research output: Contribution to journalArticle

173 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)728-733
Number of pages6
JournalNature Cell Biology
Volume13
Issue number6
DOIs
StatePublished - Jun 2011

ASJC Scopus subject areas

  • Cell Biology

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    Maddika, S., Kavela, S., Rani, N., Palicharla, V. R., Pokorny, J. L., Sarkaria, J. N., & Chen, J. (2011). WWP2 is an E3 ubiquitin ligase for PTEN. Nature Cell Biology, 13(6), 728-733. https://doi.org/10.1038/ncb2240