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Medientyp:
E-Artikel
Titel:
The Tumor Suppressor p53 Fine-Tunes Reactive Oxygen Species Levels and Neurogenesis via PI3 Kinase Signaling
Beteiligte:
Forsberg, Kirsi;
Wuttke, Anja;
Quadrato, Giorgia;
Chumakov, Peter M.;
Wizenmann, Andrea;
Di Giovanni, Simone
Erschienen:
Society for Neuroscience, 2013
Erschienen in:The Journal of Neuroscience
Sprache:
Englisch
DOI:
10.1523/jneurosci.1056-13.2013
ISSN:
0270-6474;
1529-2401
Entstehung:
Anmerkungen:
Beschreibung:
<jats:p>Mounting evidence points to a role for endogenous reactive oxygen species (ROS) in cell signaling, including in the control of cell proliferation, differentiation, and fate. However, the function of ROS and their molecular regulation in embryonic mouse neural progenitor cells (eNPCs) has not yet been clarified. Here, we describe that physiological ROS are required for appropriate timing of neurogenesis in the developing telencephalon<jats:italic>in vivo</jats:italic>and in cultured NPCs, and that the tumor suppressor p53 plays a key role in the regulation of ROS-dependent neurogenesis. p53 loss of function leads to elevated ROS and early neurogenesis, while restoration of p53 and antioxidant treatment partially reverse the phenotype associated with premature neurogenesis. Furthermore, we describe that the expression of a number of neurogenic and oxidative stress genes relies on p53 and that both p53 and ROS-dependent induction of neurogenesis depend on PI3 kinase/phospho-Akt signaling. Our results suggest that p53 fine-tunes endogenous ROS levels to ensure the appropriate timing of neurogenesis in eNPCs. This may also have implications for the generation of tumors of neurodevelopmental origin.</jats:p>