ヤマグチ　ヨウコ   Yamaguchi Yoko   山口　陽子    所属   東邦大学  薬学部 薬学科    職種   助教
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	PHLDA 1, another PHLDA family protein that inhibits Akt
掲載誌名	正式名：Cancer Science ISSNコード：1347-9032/1349-7006
掲載区分	国外
出版社	Wiley
巻・号・頁	109(11),pp.3532-3542
著者・共著者	Yu Chen,Masahiro Takikawa,Shuichi Tsutsumi,Yoko Yamaguchi,Atsushi Okabe,Mayuna Shimada,Tatsuya Kawase,Akane Sada,Issei Ezawa,Yuhei Takano,Kisaburo Nagata,Yutaka Suzuki,Kentaro Semba,Hiroyuki Aburatani,Rieko Ohki
発行年月	2018/11
概要	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.
DOI	10.1111/cas.13796
PMID	30207029
PermalinkURL	https://onlinelibrary.wiley.com/doi/pdf/10.1111/cas.13796
researchmap用URL	https://onlinelibrary.wiley.com/doi/full-xml/10.1111/cas.13796