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

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Kerr, Jeffrey B., Hutt, Karla J., Michalak, Ewa M., Cook, Michele, Vandenberg, Cassandra J., Liew, Seng H., Bouillet, Philippe, Mills, Alea, Scott, Clare L., Findlay, Jock K., Strasser, Andreas·2012·Molecular Cell
DOI 10.1016/j.molcel.2012.08.017
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Abstract

SUMMARY 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 oocytes and essential for their apoptosis triggered by DNA damage in vivo. Following γ-irradiation, induction of the pro-apoptotic 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.

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Metadata

Authors
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.
Venue
Molecular Cell
Publisher
Elsevier BV
Published
2012-11
Volume
48
Issue
3
Pages
343-352
ISSN
1097-2765 (ISSN-L)
DOI
10.1016/j.molcel.2012.08.017
OpenAlex
W2004758124
Cited by
263
References
4
FWCI
12.44
Type
journal article
Language
en
Open access
bronze
Licence

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