期刊
MOLECULAR CELL
卷 48, 期 3, 页码 343-352出版社
CELL PRESS
DOI: 10.1016/j.molcel.2012.08.017
关键词
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资金
- National Health and Medical Research Council (NHMRC Australia) [1006460, 1007027, 494802, 257502, 441101, 494836, 406675, 461299]
- Cancer Council Victoria
- Leukemia and Lymphoma Society (New York) [7015]
- National Cancer Institute (NIH) [CA 43540]
- American Cancer Society
- Victorian Cancer Agency (Clinical Fellowship)
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.
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