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The BH3-only protein Puma is both necessary and sufficient for neuronal apoptosis induced by DNA damage in sympathetic neurons

Wyttenbach, A. and Tolkovsky, A.M. (2006) The BH3-only protein Puma is both necessary and sufficient for neuronal apoptosis induced by DNA damage in sympathetic neurons Journal of Neurochemistry, 96, (5), pp. 1213-1226. (doi:10.1111/j.1471-4159.2005.03676.x).

Record type: Article

Abstract

DNA damage activates apoptosis in several neuronal populations and is an important component of neuropathological conditions. While it is well established that neuronal apoptosis, induced by DNA damage, is dependent on the key cell death regulators p53 and Bax, it is unknown which proteins link the p53 signal to Bax. Using rat sympathetic neurons as an in vitro model of neuronal apoptosis, we show that cytosine arabinoside is a DNA damaging drug that induces the expression of the BH3-only pro-apoptotic genes Noxa, Puma and Bim. Increased expression occurred after p53 activation, measured by its phosphorylation at serine 15, but prior to the conformational change of Bax at the mitochondria, cytochrome c (cyt c) release and apoptosis. Hence Noxa, Puma and Bim could potentially link p53 to Bax. We directly tested this hypothesis by the use of nullizygous mice. We show that Puma, but not Bim or Noxa, is a crucial mediator of DNA damage-induced neuronal apoptosis. Despite the powerful pro-apoptotic effects of overexpressed Puma in Bax-expressing neurons, Bax nullizygous neurons were resistant to Puma-induced death. Therefore, Puma provides the critical link between p53 and Bax, and is both necessary and sufficient to mediate DNA damage-induced apoptosis of sympathetic neurons.

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Submitted date: 30 June 2005
Published date: March 2006

Identifiers

Local EPrints ID: 37526
URI: http://eprints.soton.ac.uk/id/eprint/37526
ISSN: 0022-3042
PURE UUID: ee4b1bbe-76fc-4513-a609-65b165eb7ff2

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Date deposited: 23 May 2006
Last modified: 17 Jul 2017 15:42

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Contributors

Author: A. Wyttenbach
Author: A.M. Tolkovsky

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