title: WWP2 is an E3 ubiquitin ligase for PTEN.
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.
authors.affiliation: Laboratory of Cell Death & Cell Survival, Centre for DNA Fingerprinting and Diagnostics (CDFD), Nampally, Hyderabad 500001, India. msreddy@cdfd.org.in
authors.forename: Subbareddy
authors.initials: S
authors.lastname: Maddika
authors.forename: Sridhar
authors.initials: S
authors.lastname: Kavela
authors.forename: Neelam
authors.initials: N
authors.lastname: Rani
authors.forename: Vivek Reddy
authors.initials: VR
authors.lastname: Palicharla
authors.forename: Jenny L
authors.initials: JL
authors.lastname: Pokorny
authors.forename: Jann N
authors.initials: JN
authors.lastname: Sarkaria
authors.forename: Junjie
authors.initials: J
authors.lastname: Chen
mesh_terms: D045744:Cell Line, Tumor; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000201:enzymology / Q000503:physiopathology; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D015398:Signal Transduction; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism* / Q000502:physiology
chemical_list: C465283:WWP2 protein, human; D044767:Ubiquitin-Protein Ligases; D051059:PTEN Phosphohydrolase