1. WWP2 is an E3 ubiquitin ligase for PTEN
Jaeseung Kang

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

3. WWP2, NEDD4-1, and EDD
WWP2
NEDD4-1
EDD

4. WWP2 binds to PTEN
Co-IP between WWP2 and PTEN

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

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

7. WWP2 regulates PTEN stability

8. WWP2, Akt, and apoptosis

9. WWP2 and tumorigenesis
WWP2 promotes cell proliferation

10. WWP2 and tumorigenesis

11. 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.”

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

13. 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

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