DNA damage-inducible phosphorylation of p53 at N-terminal sites including a novel site, Ser20, requires tetramerization

Abstract

Upon DNA damage, p53 has been shown to be modified at a number of N-terminal phosphorylation sites including Ser15 and -33. Here we show that phosphorylation is induced as well at a novel site, Ser20. Phosphorylation at Ser15, -20 and -33 can occur within minutes of DNA damage. Interestingly, while the DNA-binding activities of p53 appear to be dispensable, efficient phosphorylation at these three sites requires the tetramerization domain of p53. Substitution of an artificial tetramerization domain for this region also permits phosphorylation at the N-terminus, suggesting that oligomerization is important for DNA damage-induced signalling to p53.