PHLDA1, another PHLDA family protein that inhibits Akt.
PHLDA1, another PHLDA family protein that inhibits Akt.
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DOI：
10.1111/cas.13796
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发表时间：
2018-11
期刊：
影响因子：
5.7
通讯作者：
Ohki R
中科院分区：
文献类型：
--
作者：
Chen Y;Takikawa M;Tsutsumi S;Yamaguchi Y;Okabe A;Shimada M;Kawase T;Sada A;Ezawa I;Takano Y;Nagata K;Suzuki Y;Semba K;Aburatani H;Ohki R
PHLDA家族（pleckstrin homology-like domain family）由3个成员组成：PHLDA 1、2和3。PHLDA 3和PHLDA 2都是磷脂酰肌醇（PIP）结合蛋白，并且作为Akt的阻遏物起作用。它们主要通过抑制Akt而具有肿瘤抑制作用。一些报道表明PHLDA 1也具有肿瘤抑制功能;然而，PHLDA 1的精确分子功能仍有待阐明。通过对p53靶基因的全面筛选，我们将PHLDA 1鉴定为一种新的p53靶基因，并且我们表明PHLDA 1具有以类似于PHLDA 3和PHLDA 2的方式抑制Akt的能力。PHLDA 1具有所谓的分裂PH结构域，其中PH结构域分为N末端（β折叠1 - 3）和C末端（β折叠4 - 7和α螺旋）部分。我们表明，PH结构域的PHLDA 1是负责其定位到质膜和磷脂酰肌醇结合。我们还表明，PH结构域的功能是必不可少的Akt抑制。此外，PHLDA 1表达分析表明，PHLDA 1在乳腺癌和卵巢癌中具有肿瘤抑制功能。
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.
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影响因子：
5.7
作者：
Takikawa M;Ohki R
通讯作者：
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