Neural precursor cells possess multiple p53-dependent apoptotic pathways

R. S. Akhtar, Y. Geng, B. J. Klocke, K. A. Roth*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

Neural precursor cells (NPCs) are markedly sensitive to apoptotic insults. p53-dependent transcriptional activation of proapoptotic genes has been hypothesized to regulate NPC death in response to DNA damage. Recent studies of non-NPCs have also indicated that p53 may directly interact with Bcl-2 molecules and thereby regulate death independently of transcription. The contribution of transcription-independent p53 activation in NPC death has not been characterized. In this study, we found that apoptosis caused by chemotherapeutic agents in NPCs required p53 expression and new macromolecular synthesis. In contrast, NPC death induced by staurosporine, a broad kinase inhibitor, is regulated by p53 in the absence of macromolecular synthesis. The apoptosis effector molecules Bax and Bak, Apaf-1, and caspase-9 were shown to be downstream of p53 in both pathways. These findings indicate that p53 is in a unique position to regulate at least two distinct signaling portals that activate the intrinsic apoptotic death pathway in NPCs.

Original languageEnglish (US)
Pages (from-to)1727-1739
Number of pages13
JournalCell Death and Differentiation
Volume13
Issue number10
DOIs
StatePublished - Oct 2006

Keywords

  • Bax
  • Caspase
  • Genotoxic injury
  • Neural stem cells
  • Transcription

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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