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Activation of NFAT signal by p53‐K120R mutant
Author(s) -
Shinmen Natsuko,
Koshida Toshifumi,
Kumazawa Takeshi,
Sato Keizo,
Shimada Hideaki,
Matsutani Tomoo,
Iwadate Yasuo,
Takiguchi Masaki,
Hiwasa Takaki
Publication year - 2009
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2009.04.041
Subject(s) - nfat , transactivation , acetylation , phosphorylation , mutant , luciferase , suppressor , chemistry , microbiology and biotechnology , cancer research , biology , transcription factor , biochemistry , gene , transfection
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.