A specific PP2A regulatory subunit, B56gamma, mediates DNA damage-induced dephosphorylation of p53 at Thr55.

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Li HH, Cai X, Shouse GP, Piluso LG, Liu X

A specific PP2A regulatory subunit, B56gamma, mediates DNA damage-induced dephosphorylation of p53 at Thr55.

EMBO J. 2007 Jan 24;26(2):402-11.

PubMed ID
17245430 [ View in PubMed
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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 B56gamma1 and B56gamma3 mediate dephosphorylation of p53 at Thr55. Ablation of the B56gamma 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 B56gamma protein level and association with p53 increase after DNA damage. Finally, we demonstrate that Thr55 dephosphorylation is required for B56gamma3-mediated inhibition of cell proliferation and cell transformation. These results suggest a molecular mechanism for B56gamma-mediated tumor suppression and provide a potential route for regulation of B56gamma-specific PP2A complex function.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoformP67775Details
Cellular tumor antigen p53P04637Details
Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoformQ13362Details
Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoformP30153Details
Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoformP63151Details