Cellular DNA damage causes stabilization and activation of the tumor suppressor and transcription factor p53, in part by promoting multiple covalent modifications of the p53 protein, including acetylation. We investigated the importance of acetylation in p53 function and the mechanism by which acetylation influences p53 activity.
Cellular DNA damage causes stabilization and activation of the tumor suppressor and transcription factor p53, in part by promoting multiple covalent modifications of the p53 protein, including acetylation. We investigated the importance of acetylation in p53 function and the mechanism by which acetylation influences p53 activity.
01-12-2001
 · Thus, acetylation of p53 is required for full transcriptional activation of a plasmid reporter and an endogenous p53-responsive gene. p53 functions in the G1 checkpoint in the cell cycle, responding to DNA damage by inducing genes involved in cell arrest, DNA repair, and apoptosis.
To further test the effect of acetylation on p53 transactivation independent of its own DNA binding domain, p53 was fused to a heterologous DNA binding domain (Gal4 DNA binding domain). Gal4-p53wt activated transcription 12-fold higher than Gal4 alone and Gal4-p53mut was reduced nearly 3-fold ( Figure 5C ), even though the levels of the fusion proteins were similar (lower panel).
01-12-2001
 · Cellular DNA damage causes stabilization and activation of the tumor suppressor and transcription factor p53, in part by promoting multiple covalent modifications of the p53 protein, including acetylation. We investigated the importance of acetylation in p53 function and the mechanism by which acetylation influences p53 activity.
11-04-2003
 · Co-transfection into cells of the p53 gene and plasmid DNA containing the consensus DNA binding site of p53 activated DNA-dependent acetylation of p53 in vivo. The phosphopeptide binding activity of p300 is critical for DNA-dependent acetylation, as p53 acetylation was inhibited by phospho-Ser(20) peptides.
The acetylation by p300 of these lysines in the C terminus of p53 leads to a neutralization of positive charges that in turn could disrupt the tail–core interaction and activate p53 DNA binding. To further confirm this hypothesis, we tested the effect of acetylation on the ability of the C-terminal peptide to activate p53 in trans .