Activation of NFAT signal by p53-K120R mutant.
The tumor suppressor p53 is activated by phosphorylation and/or acetylation. We constructed 14 non-phosphorylated, 11 phospho-mimetic, and 1 non-acetylated point p53 mutations and compared their transactivation ability in U-87 human glioblastoma cells by the luciferase reporter assay. Despite mutations at the phosphorylation sites, only the p53-K120R and p53-S9E mutants had marginally reduced activities. On the other hand, the Nuclear factor of activated T-cells (NFAT)-luciferase reporter was more potently activated by p53-K120R than by wild-type p53 and other mutants in glioblastoma, hepatoma and esophageal carcinoma cells. This suggests that acetylation at Lys-120 of p53 negatively regulates a signaling pathway leading to NFAT activation.
Shinmen
Natsuko
N
Department of Biochemistry and Genetics, Chiba University, Graduate School of Medicine, Chuo-ku, Chiba, Japan.
Koshida
Toshifumi
T
Kumazawa
Takeshi
T
Sato
Keizo
K
Shimada
Hideaki
H
Matsutani
Tomoo
T
Iwadate
Yasuo
Y
Takiguchi
Masaki
M
Hiwasa
Takaki
T
D000107:Acetylation; D001665:Binding Sites / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism; D017930:Genes, Reporter; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008156:Luciferases / Q000235:genetics; D008239:Lysine / Q000737:chemistry; D016297:Mutagenesis, Site-Directed; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D017354:Point Mutation; D011394:Proline Oxidase / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D015533:Transcriptional Activation; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism
D050778:NFATC Transcription Factors; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011994:Recombinant Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D008156:Luciferases; D011394:Proline Oxidase; D008239:Lysine