PIKE/nuclear PI 3-kinase signaling mediates the antiapoptotic actions of NGF in the nucleus

Jee Yin Ahn, Rong Rong, Xuesong Liu, Keqiang Ye*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

85 Citations (Scopus)

Abstract

PI 3-kinase (PBK) occurs in the nuclei of a broad range of cell types, and various stimuli elicit PI3K nuclear translocation. However, little is known about the biological function of nuclear PI3K. Here we show that nuclear PI3K and its upstream regulator PIKE mediate the antiapoptotic activity of nerve growth factor (NGF) in the isolated nuclei. The nuclei from NGF-treated PC12 cells, EGF-treated HEK293 cells and HeLa cells are resistant to DNA fragmentation initiated by activated cell-free apoptosome. Nuclei from constitutively active PI3K adenovirus-infected cells display the same resistance as those treated by NGF, whereas PI3K inhibitors, dominant-negative PI3K or PIKE abolishes it. Knockdown of either PI3K or PIKE diminishes the antiapoptotic activity of NGF. PI (3,4,5)P3 alone mimics the antiapoptotic activity of NGF, for which nuclear Akt is required. These results demonstrate that PIKE/nuclear PI3K signaling through nuclear PI (3,4,5)P3 and Akt plays an essential role in promoting cell survival.

Original languageEnglish
Pages (from-to)3995-4006
Number of pages12
JournalEMBO Journal
Volume23
Issue number20
DOIs
Publication statusPublished - 13 Oct 2004
Externally publishedYes

Keywords

  • Apoptosis
  • DNA fragmentation
  • NGF
  • Nuclear PI 3-kinase
  • PIKE

Fingerprint

Dive into the research topics of 'PIKE/nuclear PI 3-kinase signaling mediates the antiapoptotic actions of NGF in the nucleus'. Together they form a unique fingerprint.

Cite this