Diagram summarizes the inter-regulation between ASPP2 and RAS.

<p>ASPP2 binds active RAS at the plasma membrane, thereby increasing RAS signaling to its downstream pathway effectors Raf/MAPK. Activated MAPK phosphorylates ASPP2 which can then relocate to the nucleus and activate p53 pro-apoptotic signaling. </p

Wild-type ASPP2, but not mutant ASPP2 (S827A), translocates to the cytosol and nucleus upon oncogenic RAS activation and this results in an increased interaction with p53.

<p>(<b>A</b>) RAS activation induces cytoplasmic and nuclear translocation of wild-type ASPP2 but not ASPP2 (S827A) in HKe3 ER:HRAS12 cells as detected by immunofluorescence. Arrows indicate cell membrane and stars indicate cytosol. (<b>B</b>) RAS activation enhances the binding of wild-type ASPP2 but not ASPP2 (S827A) to p53. Total cell lysates from HKe3 ER:HRASV12 cells treated with or without 4-OHT were immunoprecipitated with an anti-p53 antibody or control IgG as indicated. </p

Activated Raf enhances the transactivation activity of ASPP2 and p53 to the same extent as activated RAS.

<p>(<b>A</b>) Saos2 cells were transfected as indicated with a Bax-luciferase reporter and the luciferase activity shown. * <i>P</i>=0.05 (<b>B</b>) The value of ASPP2+p53 was taken as 1.0 to reflect the fold increase of ASPP2 and p53 in the presence of activated Raf and mutant RAS. ** <i>P</i>=0.0055; **** <i>P</i>=0.0001.</p