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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
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Cytoplasmic p53 and activated Bax regulate p53-dependent, transcription-independent neural precursor cell apoptosis

Ying Geng1, K C Walls, Arindam P Ghosh

  • 1Department of Pathology, University of Alabama at Birmingham, USA.

The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society
|November 11, 2009
PubMed

Insights

Staurosporine induces neural precursor cell apoptosis through a transcription-independent pathway involving cytoplasmic p53, its interaction with Bax, and Nucleophosmin (NPM). This mechanism bypasses traditional gene upregulation for programmed cell death.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Molecular Biology

Background:

  • The tumor suppressor p53 typically induces apoptosis via transcriptional targets like PUMA, Noxa, and Bax.
  • Previous studies showed staurosporine (STS) induces p53-dependent, Bax-dependent neural precursor cell (NPC) apoptosis independently of transcription and PUMA.

Purpose of the Study:

  • To elucidate the transcription-independent mechanism of p53-mediated NPC apoptosis induced by STS.
  • To investigate the role of cytoplasmic p53 localization and interactions with other proteins in this process.

Main Methods:

  • Primary cerebellar NPCs and the C17.2 neural stem cell line from wild-type, p53-deficient, and Bax-deficient mice were used.
  • Immunofluorescence, confocal microscopy, and Western blotting were employed to assess p53 localization, Bax activation, and caspase cleavage.
  • Colocalization studies examined interactions between p53, Bax, Nucleophosmin (NPM), and mitochondria.

Main Results:

  • STS treatment rapidly increased cytoplasmic p53 in neuritic processes of C17.2 cells, preceding Bax activation and caspase-3 cleavage.
  • p53 partially colocalized with mitochondria and activated Bax, suggesting a direct role in initiating apoptosis.
  • NPM also colocalized with activated Bax and p53, indicating its involvement in the apoptotic complex.

Conclusions:

  • Cytoplasmic p53 can trigger transcription-independent NPC apoptosis.
  • This process involves interactions between p53, activated Bax, and NPM, potentially at the mitochondria.
  • The findings reveal a novel non-transcriptional apoptotic pathway regulated by p53 in neural cells.

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