DNA Damage-Induced Primordial Follicle Oocyte Apoptosis and Loss of Fertility Require TAp63-Mediated Induction of Puma and Noxa
- Author(s)
- Kerr, JB; Hutt, KJ; Michalak, EM; Cook, M; Vandenberg, CJ; Liew, SH; Bouillet, P; Mills, A; Scott, CL; Findlay, JK; Strasser, A;
- Details
- Publication Year 2012-11-09,Volume 48,Issue #3,Page 343-352
- Journal Title
- MOLECULAR CELL
- Publication Type
- Journal Article
- 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 gamma-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 gamma-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.
- Publisher
- CELL PRESS
- Keywords
- GAMMA-IRRADIATION; MOUSE OVARY; PROTEIN FAMILY; P53 HOMOLOG; CELL-DEATH; P63; BAX; LYMPHOMAGENESIS; SURVIVAL; CANCER
- Research Division(s)
- Molecular Genetics Of Cancer
- Link To PubMed Central Version
- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3496022/
- Publisher's Version
- https://doi.org/10.1016/j.molcel.2012.08.017
- Terms of Use/Rights Notice
- Copyright © 2012 Elsevier Inc. All rights reserved.
Creation Date: 2012-11-09 12:00:00