Summary
PROJECT SUMMARY: 30 lines. The canonical phosphoinositide (PI) 3-kinase (PI3K)/Akt signaling pathway uses free membrane PI lipid to regulate cell growth and is frequently hyperactivated in cancer. Akt is also activated in the nucleus by poorly understood mechanisms. We discovered a nuclear PI3K/Akt pathway composed of PI kinases/phosphatases that modify phosphatidylinositol phosphates (PIPns) linked to p53 (p53-PIPn signalosome). PIPKI synthesizes p53-PIP2 that stabilizes it and regulates MDM2. The PI3K inositol polyphosphate multikinase (IPMK) converts p53-PIP2 to p53-PIP3, which is reversed
