Activation of NFAT signal by p53-K120R mutant

Shinmen, Natsuko; Koshida, Toshifumi; Kumazawa, Takeshi; Sato, Keizo; Shimada, Hideaki; Matsutani, Tomoo; Iwadate, Yasuo; Takiguchi, Masaki; Hiwasa, Takaki

doi:10.1016/j.febslet.2009.04.041

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Volume 583, Issue 12 , Pages 1916-1922, 18 June 2009

Activation of NFAT signal by p53-K120R mutant

Edited by Varda Rotter

Natsuko Shinmen
- Department of Biochemistry and Genetics, Chiba University, Graduate School of Medicine, Inohana 1-8-1, Chuo-ku, Chiba 260-8670, Japan
- Department of Legal Medicine, Showa University School of Medicine, Hatanodai 1-5-8, Shinagawa-ku, Tokyo 142-8555, Japan
Toshifumi Koshida
- Department of Biochemistry and Genetics, Chiba University, Graduate School of Medicine, Inohana 1-8-1, Chuo-ku, Chiba 260-8670, Japan
Takeshi Kumazawa
- Department of Legal Medicine, Showa University School of Medicine, Hatanodai 1-5-8, Shinagawa-ku, Tokyo 142-8555, Japan
Keizo Sato
- Department of Legal Medicine, Showa University School of Medicine, Hatanodai 1-5-8, Shinagawa-ku, Tokyo 142-8555, Japan
Hideaki Shimada
- Department of Gastroenterological Surgery, Chiba Cancer Center, Nitona-cho 666-2, Chuo-ku, Chiba 260-8717, Japan
Tomoo Matsutani
- Department of Neurological Surgery, Chiba University, Graduate School of Medicine, Inohana 1-8-1, Chuo-ku, Chiba 260-8670, Japan
Yasuo Iwadate
- Department of Neurological Surgery, Chiba University, Graduate School of Medicine, Inohana 1-8-1, Chuo-ku, Chiba 260-8670, Japan
Masaki Takiguchi
- Department of Biochemistry and Genetics, Chiba University, Graduate School of Medicine, Inohana 1-8-1, Chuo-ku, Chiba 260-8670, Japan
Takaki Hiwasa
- Department of Biochemistry and Genetics, Chiba University, Graduate School of Medicine, Inohana 1-8-1, Chuo-ku, Chiba 260-8670, Japan
- Corresponding author. Fax: +81 43 226 2037.

Received 3 April 2009; accepted 27 April 2009. published online 04 May 2009.

Abstract

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.

Keywords: Nuclear factor of activated T-cell, p53, Luciferase reporter assay, Calcium signal