Journal article
DNA Damage-Induced Primordial Follicle Oocyte Apoptosis and Loss of Fertility Require TAp63-Mediated Induction of Puma and Noxa
JB Kerr, KJ Hutt, EM Michalak, M Cook, CJ Vandenberg, SH Liew, P Bouillet, A Mills, CL Scott, JK Findlay, A Strasser
Molecular Cell | CELL PRESS | Published : 2012
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 criti..
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Awarded by National Institutes of Health
Funding Acknowledgements
We thank Professors J.M. Adams, S. Cory, and A. Villunger for gifts of mice, G. Tarulli and H. Morgan for assistance with histology, and E. Jansen for technical assistance and Drs. G. Enders, R. Schultz, and F. McKeon for gifts of antibodies. This work was supported by fellowships and grants from the National Health and Medical Research Council (NHMRC Australia; project grants #1006460 and #1007027, program grants #494802 and #257502, and fellowships to J.K.F. [#441101], K.J.H. [#494836], C.L.S. [#406675], and A.S. [#461299]), the Cancer Council Victoria (E.M.M. and Sir Edward Dunlop Cancer Research Fellow to C.L.S.), the Leukemia and Lymphoma Society (New York; SCOR grant #7015), the National Cancer Institute (NIH; CA 43540), the American Cancer Society (A.A.M.), and the Victorian Cancer Agency (Clinical Fellowship to C.L.S.). This work was made possible through Victorian State Government Operational Infrastructure Support and Australian Government NHMRC Independent Research Institutes Infrastructure Support Scheme (IRIISS). J.B.K., K.J.H., and E.M.M. performed and planned experiments, interpreted data, and wrote the manuscript. M.C., C.V., and S.H.L. helped with experiments and contributed data. P.B. and A.M. contributed essential reagents and helped with interpretation of results and manuscript writing. A.S., J.K.F., and C.L.S. conceived of the study, planned experiments, interpreted data, and wrote the manuscript.