DNA Damage-Induced Primordial Follicle Oocyte Apoptosis and Loss of Fertility Require TAp63-Mediated Induction of Puma and Noxa

Kerr, J. B., Hutt, K. J, Michalak, E. M., Cook, M., Vandenberg, C. J., Liew, S. H., Bouillet, P., Mills, A., Scott, C. L., Findlay, J. K., Strasser, A. (November 2012) DNA Damage-Induced Primordial Follicle Oocyte Apoptosis and Loss of Fertility Require TAp63-Mediated Induction of Puma and Noxa. Molecular Cell, 48 (3). pp. 343-352. ISSN 1097-2765

URL: http://www.ncbi.nlm.nih.gov/pubmed/23000175

DOI: 10.1016/j.molcel.2012.08.017

Abstract

Trp63, a transcription factor related to the tumor suppressor p53, is activated by diverse stimuli and can initiate a range of cellular responses. TAp63 is the predominant Trp53 family member in primordial follicle oocyte nuclei and is essential for their apoptosis triggered by DNA damage in vivo. After γ-irradiation, induction of the proapoptotic BH3-only members Puma and Noxa was observed in primordial follicle oocytes from WT and Trp53(-/-) mice but not in those from TAp63-deficient mice. Primordial follicle oocytes from mice lacking Puma or both Puma and Noxa were protected from γ-irradiation-induced apoptosis and, remarkably, could produce healthy offspring. Hence, PUMA and NOXA are critical for DNA damage-induced, TAp63-mediated primordial follicle oocyte apoptosis. Thus, blockade of PUMA may protect fertility during cancer therapy and prevent premature menopause, improving women's health.

Item Type:	Paper
Subjects:	bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification 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 functions organs, tissues, organelles, cell types and functions > cell types and functions organs, tissues, organelles, cell types and functions bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > transcription factor
CSHL Authors:	Mills, Alea A.
Communities:	CSHL Cancer Center Program > Cancer Genetics CSHL Cancer Center Shared Resources > Animal Services CSHL Cancer Center Shared Resources > Gene Targeting Service CSHL labs > Mills lab CSHL Cancer Center Shared Resources > Functional Genomics and Genetics Service
Depositing User:	Matt Covey
Date:	9 November 2012
Date Deposited:	30 Jan 2013 19:35
Last Modified:	30 Oct 2015 16:41
PMCID:	PMC3496022
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/26976

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