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FEBS Lett. 2009 May 6;583(9):1516-20. doi: 10.1016/j.febslet.2009.04.008. Epub 2009 Apr 11.

Essential role of p53 in TPEN-induced neuronal apoptosis.

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  • 1Department of Molecular Biology, Sejong University, 98 Gunja-Dong Gwangjin-Gu, Seoul 143-747, South Korea.


Depletion of intracellular zinc with N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) induces protein synthesis-dependent apoptosis. In this study, we examined the requirement for p53 as an upstream transcription factor in TPEN-induced neuronal apoptosis. Chemical or genetic blockade of p53 markedly attenuated TPEN-induced neuronal apoptosis, while the stability and activity of p53 were increased by TPEN. In addition, expression of proapoptotic genes, PUMA and NOXA, and activation of caspase-11 were increased by TPEN in a p53-dependent manner. Inhibition of p53 blocked cytochrome C release from mitochondria to cytosol and prevented caspase-3 activation. Therefore, p53 may be an essential regulatory factor for TPEN-induced neuronal apoptosis.

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