Neural precursor cells possess multiple p53-dependent apoptotic pathways

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

doi:10.1038/sj.cdd.4401879

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 journal › Article › peer-review

35 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 language	English (US)
Pages (from-to)	1727-1739
Number of pages	13
Journal	Cell Death and Differentiation
Volume	13
Issue number	10
DOIs	https://doi.org/10.1038/sj.cdd.4401879
State	Published - Oct 2006
Externally published	Yes

Funding

We would like to thank Dr. Steven L Carroll for helpful discussions regarding real time RT-PCR techniques, Dr. John J Shacka for critical review of this manuscript, and Ms. Cecelia B Latham for technical assistance. This work was supported by grants from the National Institutes of Health (NS35107 and NS41962). RSA is supported by the UAB Medical Scientist Training Program (GM008361). The nestin antibody developed by Susan Hockfield was obtained from the Developmental Studies Hybridoma Bank developed under the auspices of the NICHD and maintained by The University of Iowa, Department of Biological Sciences, Iowa City, IA 52242, USA.

Keywords

Bax
Caspase
Genotoxic injury
Neural stem cells
Transcription

ASJC Scopus subject areas

Molecular Biology
Cell Biology

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10.1038/sj.cdd.4401879

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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.",

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Neural precursor cells possess multiple p53-dependent apoptotic pathways

Abstract

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Keywords

ASJC Scopus subject areas

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