WWP2 is an E3 ubiquitin ligase for PTEN

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Presentation transcript:

WWP2 is an E3 ubiquitin ligase for PTEN Jaeseung Kang 20128001

WWP2: E3 ubiquitin ligase C2 E3-ligase domain WW domain HECT domain Found in mass spectrometry

WWP2, NEDD4-1, and EDD WWP2 NEDD4-1 EDD

WWP2 binds to PTEN Co-IP between WWP2 and PTEN

WWP2 binding region of PTEN Phosphatase domain of PTEN is WWP2 binding region

WWP2 regulates PTEN stability WWP catalytic activity is necessary for PTEN ubiquitination

WWP2 regulates PTEN stability

WWP2, Akt, and apoptosis

WWP2 and tumorigenesis WWP2 promotes cell proliferation

WWP2 and tumorigenesis

NEDD4-1? “we failed to detect the interaction of PTEN with NEDD4-1 or a PTEN-associated E3 ligase activity. Although our NEDD4-1 siRNA-mediated knockdown studies (data not shown) showed a reduced rate of cell proliferation, this might not be dependent on PTEN because we observed a similar effect of NEDD4-1 knockdown on cell proliferation in PTEN-deficient cells.”

Intracellular localization? PTEN polyubiquitination might affect PTEN nuclear localization (NOT related to WWP2)

Summary WWP2 ubiquitinates PTEN WWP2 regulates PTEN stability via ubiquitination WWP2 controls cell proliferation and tumorigenesis in PTEN-dependent manner NEDD4-1 is NOT a PTEN ubiquitin E3 ligase

Discussion C2 ubiquitin E3 ligase domain? Other proteins containing C2 domain? Possibility of “Multi-E3-ligase hypothesis”? E3 ligases and nuclear localization of PTEN?