@article{7eb01af361c24651baf256b0e587ce12,
title = "PHLDA1, another PHLDA family protein that inhibits Akt",
abstract = "The PHLDA family (pleckstrin homology-like domain family) of genes consists of 3 members: PHLDA1, 2, and 3. Both PHLDA3 and PHLDA2 are phosphatidylinositol (PIP) binding proteins and function as repressors of Akt. They have tumor suppressive functions, mainly through Akt inhibition. Several reports suggest that PHLDA1 also has a tumor suppressive function; however, the precise molecular functions of PHLDA1 remain to be elucidated. Through a comprehensive screen for p53 target genes, we identified PHLDA1 as a novel p53 target, and we show that PHLDA1 has the ability to repress Akt in a manner similar to that of PHLDA3 and PHLDA2. PHLDA1 has a so-called split PH domain in which the PH domain is divided into an N-terminal (β sheets 1-3) and a C-terminal (β sheets 4-7 and an α-helix) portions. We show that the PH domain of PHLDA1 is responsible for its localization to the plasma membrane and binding to phosphatidylinositol. We also show that the function of the PH domain is essential for Akt repression. In addition, PHLDA1 expression analysis suggests that PHLDA1 has a tumor suppressive function in breast and ovarian cancers.",
keywords = "Akt, PH domain, PHLDA family, p53, tumor suppressor",
author = "Yu Chen and Masahiro Takikawa and Shuichi Tsutsumi and Yoko Yamaguchi and Atsushi Okabe and Mayuna Shimada and Tatsuya Kawase and Akane Sada and Issei Ezawa and Yuhei Takano and Kisaburo Nagata and Yutaka Suzuki and Kentaro Semba and Hiroyuki Aburatani and Rieko Ohki",
note = "Funding Information: We thank Marc Lamphier for critical reading of the manuscript. This study was partly supported by a Grant‐in‐Aid for Scientific Research (B) (#17H03587) (R.O.), Grant‐in‐Aid for Research Activity start‐up (#17H07378) (M.T.), and Grant‐in‐Aid for Young Scientist (B) (#15K19537) (Y.Y.) from the Ministry of Education, Culture, Sports, Science and Technology of Japan, Applied Research for Innovative Treatment of Cancer from the Ministry of Health, Labour and Welfare (R.O.), Development of Innovative Research on Cancer Therapeutics (P‐DIRECT)/Ministry of Education, Culture, Sports, Science and Technology of Japan (R.O.), research grants from Research Grant of the Princess Takamatsu Cancer Research Fund (R.O.), the Mit-subishi Foundation (to R.O.), the Novartis Foundation (Japan) for the Promotion of Science (to R.O.), the Project Mirai Cancer Research Grants (R.O.), the Okinaka Memorial Institute for Medical Research (to R.O.), the National Cancer Center Research and Development Fund (to R.O., 29‐E‐2), the Life Science Foundation of Japan (to R.O.), and Foundation for Promotion of Cancer Research in Japan (to R.O.). Funding Information: The Ministry of Education, Culture, Sports, Science and Technology of Japan, Grant/ Award Number: #17H03587, #17H07378, #15K19537; Research for Innovative Treatment of Cancer from the Ministry of Health, Labour and Welfare; Development of Innovative Research on Cancer Therapeutics P-DIRECT/Ministry of Education, Culture, Sports, Science and Technology of Japan; Princess Takamatsu Cancer Research; The Mitsubishi Foundation; The NOVARTIS Foundation (Japan) for the Promotion of Science; The Project Mirai Cancer Research; The Okinaka Memorial Institute for Medical Research; The National Cancer Center Research and Development Fund; The Life Science Foundation of Japan; Foundation for Promotion of Cancer Research in Japan; Applied Research for Innovative Treatment of Cancer from the Ministry of Health, Labour and Welfare Publisher Copyright: {\textcopyright} 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.",
year = "2018",
month = nov,
doi = "10.1111/cas.13796",
language = "English",
volume = "109",
pages = "3532--3542",
journal = "Cancer Science",
issn = "1347-9032",
publisher = "Wiley-Blackwell",
number = "11",
}