title: Phosphorylation at Ser-15 and Ser-392 in mutant p53 molecules from human tumors is altered compared to wild-type p53.
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.
authors.affiliation: Laboratory of Cell Biology, National Cancer Institute, Bethesda, MD 20892.
authors.forename: S J
authors.initials: SJ
authors.lastname: Ullrich
authors.forename: K
authors.initials: K
authors.lastname: Sakaguchi
authors.forename: S P
authors.initials: SP
authors.lastname: Lees-Miller
authors.forename: M
authors.initials: M
authors.lastname: Fiscella
authors.forename: W E
authors.initials: WE
authors.lastname: Mercer
authors.forename: C W
authors.initials: CW
authors.lastname: Anderson
authors.forename: E
authors.initials: E
authors.lastname: Appella
mesh_terms: D000595:Amino Acid Sequence; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D010748:Phosphopeptides / Q000032:analysis; D010766:Phosphorylation; D012694:Serine / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D010748:Phosphopeptides; D016159:Tumor Suppressor Protein p53; D012694:Serine