DNA damage-inducible phosphorylation of p53 at N-terminal sites including a novel site, Ser20, requires tetramerization - PubMed (original) (raw)
DNA damage-inducible phosphorylation of p53 at N-terminal sites including a novel site, Ser20, requires tetramerization
S Y Shieh et al. EMBO J. 1999.
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.
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References
- Oncogene. 1995 May 4;10(9):1865-8 - PubMed
- Cancer Res. 1995 Jun 1;55(11):2410-7 - PubMed
- Nat Struct Biol. 1994 Dec;1(12):877-90 - PubMed
- Oncogene. 1995 Jun 1;10(11):2095-101 - PubMed
- Adv Cancer Res. 1995;66:143-80 - PubMed
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