Serine 15 phosphorylation of p53 directs its interaction with B56 gamma and the tumor suppressor activity of B56 gamma-specific protein phosphatase 2A

Earlier studies have demonstrated a functional link between B56 gamma-specific protein phosphatase 2A (B56 gamma-PP2A) and p53 tumor suppressor activity. Upon DNA damage, a complex including B56 gamma-PP2A and p53 is formed which leads to Thr55 dephosphorylation of p53, induction of the p53 transcriptional target p21, and the inhibition of cell proliferation. Although an enhanced interaction between p53 and B56 gamma is observed after DNA damage, the underlying mechanism and its significance in PP2A tumor-suppressive function remain unclear. In this study, we show that the increased interaction between B56 gamma and p53 after DNA damage requires ATM-dependent phosphorylation of p53 at Ser15. In addition, we demonstrate that the B56 gamma 3-induced inhibition of cell proliferation, induction of cell cycle arrest in G(1), and blockage of anchorage-independent growth are also dependent on Ser15 phosphorylation of p53 and p53-B56 gamma interaction. Taken together, our results provide a mechanistic link between Ser15 phosphorylation-mediated p53-B56 gamma interaction and the modulation of p53 tumor suppressor activity by PP2A. We also show an important link between ATM activity and the tumor-suppressive function of B56 gamma-PP2A.