A specific PP2A regulatory subunit, B56γ, mediates DNA damage-induced dephosphorylation of p53 at Thr55

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Abstract
Protein phosphatase 2A (PP2A) has been implicated to exert its tumor suppressive function via a small subset of regulatory subunits. In this study, we reported that the specific B regulatory subunits of PP2A B56γ1 and B56γ3 mediate dephosphorylation of p53 at Thr55. Ablation of the B56γ protein by RNAi, which abolishes the Thr55 dephosphorylation in response to DNA damage, reduces p53 stabilization, Bax expression and cell apoptosis. To investigate the molecular mechanisms, we have shown that the endogenous B56γ protein level and association with p53 increase after DNA damage. Finally, we demonstrate that Thr55 dephosphorylation is required for B56γ3‐mediated inhibition of cell proliferation and cell transformation. These results suggest a molecular mechanism for B56γ‐mediated tumor suppression and provide a potential route for regulation of B56γ‐specific PP2A complex function.