DNA Damage-Induced Primordial Follicle Oocyte Apoptosis and Loss of Fertility Require TAp63-Mediated Induction of Puma and Noxa
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
WEHI Research Division(s)
Molecular Genetics Of Cancer
Rights Notice
Copyright © 2012 Elsevier Inc. All rights reserved.


Creation Date: 2012-11-09 12:00:00
Last Modified: 0001-01-01 12:00:00
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