In:
Cancer Science, Wiley, Vol. 109, No. 11 ( 2018-11), p. 3532-3542
Abstract:
The PHLDA family (pleckstrin homology‐like domain family) of genes consists of 3 members: PHLDA 1 , 2 , and 3 . Both PHLDA 3 and PHLDA 2 are phosphatidylinositol ( PIP ) binding proteins and function as repressors of Akt. They have tumor suppressive functions, mainly through Akt inhibition. Several reports suggest that PHLDA 1 also has a tumor suppressive function; however, the precise molecular functions of PHLDA 1 remain to be elucidated. Through a comprehensive screen for p53 target genes, we identified PHLDA 1 as a novel p53 target, and we show that PHLDA 1 has the ability to repress Akt in a manner similar to that of PHLDA 3 and PHLDA 2. PHLDA 1 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 PHLDA 1 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, PHLDA 1 expression analysis suggests that PHLDA 1 has a tumor suppressive function in breast and ovarian cancers.
Type of Medium:
Online Resource
ISSN:
1347-9032
,
1349-7006
DOI:
10.1111/cas.2018.109.issue-11
Language:
English
Publisher:
Wiley
Publication Date:
2018
detail.hit.zdb_id:
2115647-5
detail.hit.zdb_id:
2111204-6
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