p63 is an essential proapoptotic protein during neural development

Jacobs, W. B., Govoni, G., Ho, D., Atwal, J. K., Barnabe-Heider, F., Keyes, W. M., Mills, A. A., Miller, F. D., Kaplan, D. R. (December 2005) p63 is an essential proapoptotic protein during neural development. Neuron, 48 (5). pp. 743-756. ISSN 0896-6273

Abstract

The p53 family member p63 is required for nonneural development, but has no known role in the nervous system. Here, we define an essential proapoptotic role for p63 during naturally occurring neuronal death. Sympathetic neurons express full-length TAp63 during the developmental death period, and TAp63 levels increase following NGF withdrawal. Overexpression of TAp63 causes neuronal apoptosis in the presence of NGF, while cultured p63(-/-) neurons are resistant to apoptosis following NGF withdrawal. TAp63 is also essential in vivo, since embryonic p63(-/-) mice display a deficit in naturally occurring sympathetic neuron death. While both TAp63 and p53 induce similar apoptotic signaling proteins and require BAX expression and function for their effects, TAp63 induces neuronal death in the absence of p53, but p53 requires coincident p63 expression for its proapoptotic actions. Thus, p63 is essential for developmental neuronal death, likely functioning both on its own, and as an obligate proapoptotic partner for p53.

Item Type:	Paper
Uncontrolled Keywords:	cytochrome-c release neural survival programmed cell death P53 FAMILY P53_dependent apoptosis sympathetic neurons tumor suppressor tumor-suppressor NERVOUS-SYSTEM p73 BAX NGF
Subjects:	bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > NMDA receptor organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > apoptosis organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > p63
CSHL Authors:	Mills, Alea A. Keyes, William M.
Communities:	CSHL labs > Mills lab
Depositing User:	CSHL Librarian
Date:	December 2005
Date Deposited:	12 Jan 2012 21:40
Last Modified:	02 Feb 2017 17:35
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/22607

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