Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):5954-8.

Phosphorylation at Ser-15 and Ser-392 in mutant p53 molecules from human tumors is altered compared to wild-type p53.

Ullrich SJ, Sakaguchi K, Lees-Miller SP, Fiscella M, Mercer WE, Anderson CW, Appella E.

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Laboratory of Cell Biology, National Cancer Institute, Bethesda, MD 20892.

Abstract

The product of the p53 gene suppresses cell growth and plays a critical role in suppressing development of human tumors. p53 protein binds DNA, activates transcription, and can be phosphorylated at N- and C-terminal sites. Previously, wild-type p53 was shown to be hyperphosphorylated compared to mutant p53 during p53-mediated growth arrest in vivo. Here we show that Ser-15 and Ser-9 in the N-terminal transactivation domain of wild-type human p53 are phosphorylated in vivo in cells derived from the human glioblastoma line T98G. In [Ile237]p53 and [Ala143]p53, two natural p53 mutants from human tumors that are defective for activation of transcription, phosphorylation at Ser-15 was reduced and phosphorylation at Ser-392 was increased compared to wild-type p53. No change was observed at Ser-9. [His273]p53, a third mutant, had a phosphorylation state similar to that of wild-type p53. We suggest that phosphorylation of Ser-15 may depend on the ability of p53 to adopt a wild-type conformation and may contribute to p53's ability to block cell growth.

PMID:: 8327466; [PubMed - indexed for MEDLINE]
PMCID: PMC46845

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Serine

MW: 105.09 g/mol

MF: C₃H₇NO₃

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