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Physical interactions and functional coupling between Daxx and sodium hydrogen exchanger 1 in ischemic cell death

Yong-Sam Jung1, Hye-Young Kim, Juno Kim

  • 1School of Bioscience & Biotechnology, Chungnam National University, 220 Gung-dong, Yuseong-gu, Daejeon 305-764, South Korea.

The Journal of Biological Chemistry
|November 16, 2007
PubMed

Insights

Daxx protein moves to the cytoplasm during ischemic stress, activating the Sodium Hydrogen Exchanger (NHE1) and suppressing the NHE1-ezrin-Akt-1 pathway, revealing its role in cell death.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Physiology

Background:

  • Daxx (death domain-associated protein) is involved in ischemic cell death.
  • The precise mechanism of Daxx-mediated cell death remains unclear.

Purpose of the Study:

  • To elucidate the mechanism of Daxx-mediated cell death.
  • To identify proteins interacting with Daxx during ischemic stress.

Main Methods:

  • Yeast two-hybrid assay to identify Daxx-interacting proteins.
  • Cellular localization studies of Daxx during ischemia.
  • Transfection of Daxx mutants to assess functional consequences.
  • Measurement of intracellular pH recovery from acid load.

Main Results:

  • Sodium hydrogen exchanger isoform 1 (NHE1) was identified as a Daxx-interacting protein.
  • Daxx translocates from the nucleus to the cytoplasm during ischemia, colocalizing with NHE1.
  • Cytoplasmic Daxx activates NHE1 activity and suppresses the NHE1-ezrin-Akt-1 pathway.

Conclusions:

  • Daxx acts as an upstream regulator of NHE1 in ischemic cell death.
  • Ischemic insult induces Daxx translocation, leading to cytoplasmic Daxx-mediated NHE1 activation.
  • Daxx's interaction with NHE1 modulates cellular pH regulation and survival pathways.

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