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Science 289 (5477): 304-306

Copyright © 2000 by the American Association for the Advancement of Science

An Anti-Apoptotic Role for the p53 Family Member, p73, During Developmental Neuron Death

Christine D. Pozniak, 1 Stevo Radinovic, 2 Annie Yang, 3 Frank McKeon, 3 David R. Kaplan, 12 Freda D. Miller 1*

p53 plays an essential pro-apoptotic role, a function thought to be shared with its family members p73 and p63. Here, we show that p73 is primarily present in developing neurons as a truncated isoform whose levels are dramatically decreased when sympathetic neurons apoptose after nerve growth factor (NGF) withdrawal. Increased expression of truncated p73 rescues these neurons from apoptosis induced by NGF withdrawal or p53 overexpression. In p73-/- mice, all isoforms of p73 are deleted and the apoptosis of developing sympathetic neurons is greatly enhanced. Thus, truncated p73 is an essential anti-apoptotic protein in neurons, serving to counteract the pro-apoptotic function of p53.

1 Center for Neuronal Survival,
2 Brain Tumor Research Center, Montreal Neurological Institute, McGill University, Montreal, Canada H3A 2B4.
3 Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
*   To whom correspondence should be addressed. E-mail: mdfm{at}musica.mcgill.ca

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   Abstract »    Full Text »    PDF »
TrkA mediates developmental sympathetic neuron survival in vivo by silencing an ongoing p75NTR-mediated death signal.
M. Majdan, G. S. Walsh, R. Aloyz, and F. D. Miller (2001)
J. Cell Biol. 155, 1275-1286
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