Phosphorylation of p53 serine 15 increases interaction with CBP.
p53 exerts its cell cycle regulatory effects through its ability to function as a sequence-specific DNA binding transcription factor. CREB-binding protein (CBP)/p300, through its interaction with the N terminus of p53, acts as a coactivator for p53 and increases the sequence-specific DNA-binding activity of p53 by acetylating its C terminus. The same N-terminal domain of p53 has recently been shown to be phosphorylated at Ser15 in response to gamma-irradiation. Remarkably, we now demonstrate that phosphorylation of p53 at Ser15 increases its ability to recruit CBP/p300. The increase in CBP/p300 binding was followed by an increase in the overall level of acetylation of the C terminus of p53. These results provide a mechanism for the activation of p53-regulated genes following DNA damage, through a signaling pathway linking p53 N-terminal kinase and C-terminal acetyltransferase activities.
Lambert
P F
PF
Virus Tumor Biology Section, Laboratory of Receptor Biology and Gene Expression, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA.
Kashanchi
F
F
Radonovich
M F
MF
Shiekhattar
R
R
Brady
J N
JN
D000107:Acetylation; D050882:CREB-Binding Protein; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins; D006367:HeLa Cells; D006801:Humans; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011839:Radiation, Ionizing; D012694:Serine / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53; D012694:Serine; D050882:CREB-Binding Protein; C494363:CREBBP protein, human; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; D017346:Protein Serine-Threonine Kinases