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Subba Reddy, Maddika and Sridhar, K. and Rani, N. and Vivek Reddy, P. and Pokorny, J.L. and Sarkaria, J.N. and Chen, J. (2011) WWP2 is an E3 ubiquitin ligase for PTEN. Nature Cell Biology, 13 (6). pp. 728-732. ISSN 1465-7392

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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.

Item Type: Article
Depositing User: Dr P Divakar
Date Deposited: 01 Sep 2015 11:22
Last Modified: 21 Sep 2015 05:57
URI: http://cdfd.sciencecentral.in/id/eprint/434

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