GSK3 beta N-terminus binding to p53 promotes its acetylation

The prevalence in human cancers of mutations in p53 exemplifies its crucial role as a tumor suppressor transcription factor. Previous studies have shown that the constitutively active serine/threonine kinase glycogen synthase kinase-3beta (GSK3 beta) associates with the C-terminal basic domain of p53 and regulates its actions. In this study we identified the GSK3 beta N-terminal amino acids 78-92 as necessary for its association with p53. Inhibitors of GSK3 impaired the acetylation of p53 at Lys373 and Lys382 near the GSK3 beta binding region in p53, indicating that GSK3 beta facilitates p53 acetylation. We also found that acetylation of p53 reduced its association with GSK3 beta, as well as with GSK3alpha. These results indicate that the N-terminal region of GSK3 beta binds p53, this association promotes the acetylation of p53, and subsequently acetylated p53 dissociates from GSK3.