Figure 1.

PHLDA3 is a target gene of p53 and encodes a protein that functions as an endogenous inhibitor of Akt. (A) A schematic diagram of PHLDA3. Pleckstrin Homology (PH) domain is the only known protein domain in PHLDA3. (B) A model of Akt repression by PHLDA3. PHLDA3 functions as a dominant negative repressor of Akt. PHLDA3 localizes to the plasma membrane via binding to phosphatidylinositol phosphates (PIPs), thereby competing with Akt binding to PIPs and suppressing Akt-mediated survival signaling.