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

被引：203

作者：

Kerr, Jeffrey B. ^{[2
]}

Hutt, Karla J. ^{[2
,3
]}

Michalak, Ewa M. ^{[1
,4
]}

Cook, Michele ^{[1
]}

Vandenberg, Cassandra J. ^{[1
,4
]}

Liew, Seng H. ^{[3
]}

Bouillet, Philippe ^{[1
,4
]}

Mills, Alea ^{[5
]}

Scott, Clare L. ^{[1
,4
]}

Findlay, Jock K. ^{[3
]}

Strasser, Andreas ^{[1
,4
]}

机构：

[1] Walter & Eliza Hall Inst Med Res, Parkville, Vic 3052, Australia

[2] Monash Univ, Dept Anat & Dev Biol, Clayton, Vic 3168, Australia

[3] Prince Henrys Inst Med Res, Clayton, Vic 3168, Australia

[4] Univ Melbourne, Dept Med Biol, Parkville, Vic 3052, Australia

[5] Cold Spring Harbor Labs, Cold Spring Harbor, NY 11724 USA

来源：

MOLECULAR CELL | 2012年 / 48卷 / 03期

基金：

英国医学研究理事会;

关键词：

GAMMA-IRRADIATION; MOUSE OVARY; PROTEIN FAMILY; P53; HOMOLOG; CELL-DEATH; P63; BAX; LYMPHOMAGENESIS; SURVIVAL; CANCER;

D O I：

10.1016/j.molcel.2012.08.017

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：343 / 352

页数：10

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