Distinct pattern of p53 phosphorylation in human tumors.
The protein product of the tumor suppressor gene p53 is phosphorylated on multiple residues by several protein kinases. Using a battery of 10 antibodies developed against different phosphorylated and acetylated residues of p53, we compared the pattern of p53 phosphorylation and acetylation in tumor-derived cell lines, tumor samples, and non-neoplastic cells. Irrespective of tumor types or the presence of p53 mutation, phosphorylation and acetylation of p53 was substantially higher in samples obtained from tumor tissues than those found in non-transformed samples. Among the 10 sites analysed, phosphorylation of residues 15, 81, 392, and acetylation were among the more frequent modifications. Analysis of two of the more abundant phosphorylation or acetylation sites on p53 is sufficient to detect 72% of tumor-derived p53 proteins. The distinct pattern of p53 phosphorylation and acetylation in human tumors may offer a new means to monitor the status and activity of p53 in the course of tumor development and progression.
Minamoto
T
T
Cancer Research Institute, Kanazawa University, Kanazawa, Japan.
Buschmann
T
T
Habelhah
H
H
Matusevich
E
E
Tahara
H
H
Boerresen-Dale
A L
AL
Harris
C
C
Sidransky
D
D
Ronai
Z
Z
D000107:Acetylation; D019943:Amino Acid Substitution; D015153:Blotting, Western; D005347:Fibroblasts / Q000378:metabolism; D016158:Genes, p53; D006801:Humans; D020125:Mutation, Missense; D009363:Neoplasm Proteins / Q000737:chemistry* / Q000235:genetics; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D014407:Tumor Cells, Cultured / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry*
D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53; D011494:Protein Kinases