Journal Article10.1038/NATURE05337
p63 protects the female germ line during meiotic arrest
Eun Kyung Suh,Annie Yang,Arminja N. Kettenbach,Casimir Bamberger,Ala H. Michaelis,Zhou Zhu,Julia A. Elvin,Roderick T. Bronson,Christopher P. Crum,Frank McKeon +9 more
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TL;DR: It is shown that the p53 homologue p63, and specifically the TAp63 isoform, is constitutively expressed in female germ cells during meiotic arrest and is essential in a process of DNA damage-induced oocyte death not involving p53.
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Abstract: Meiosis in the female germ line of mammals is distinguished by a prolonged arrest in prophase of meiosis I between homologous chromosome recombination and ovulation. How DNA damage is detected in these arrested oocytes is poorly understood, but it is variably thought to involve p53, a central tumour suppressor in mammals. While the function of p53 in monitoring the genome of somatic cells is clear, a consensus for the importance of p53 for germ line integrity has yet to emerge. Here we show that the p53 homologue p63 (refs 5, 6), and specifically the TAp63 isoform, is constitutively expressed in female germ cells during meiotic arrest and is essential in a process of DNA damage-induced oocyte death not involving p53. We also show that DNA damage induces both the phosphorylation of p63 and its binding to p53 cognate DNA sites and that these events are linked to oocyte death. Our data support a model whereby p63 is the primordial member of the p53 family and acts in a conserved process of monitoring the integrity of the female germ line, whereas the functions of p53 are restricted to vertebrate somatic cells for tumour suppression. These findings have implications for understanding female germ line fidelity, the regulation of fertility and the evolution of tumour suppressor mechanisms.
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Citations
How does p53 induce apoptosis and how does this relate to p53-mediated tumour suppression?
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TL;DR: The role of the DNA damage response, which is activated during the early stages of tumour development, in mobilizing the tumour suppression function of p53 is considered.
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References
Biochemical Pathways of Caspase Activation During Apoptosis
TL;DR: This review focuses on the two most well-studied pathways of caspase activation: the cell surface death receptor pathway and the mitochondria-initiated pathway.
2.7K
p53: puzzle and paradigm.
Linda J. Ko,Carol Prives +1 more
TL;DR: Some of the key developments leading to the current state of knowledge in p53 research are presented and how they either shed light on or add to the complexities of p53 are discussed.
p63 is essential for regenerative proliferation in limb, craniofacial and epithelial development
Annie Yang,Ronen Schweitzer,Deqin Sun,Mourad Kaghad,Nancy Walker,Roderick T. Bronson,Clifford J. Tabin,Arlene H. Sharpe,Daniel Caput,Christopher P. Crum,Frank McKeon +10 more
TL;DR: It is reported that mice homozygous for a disrupted p63 gene have major defects in their limb, craniofacial and epithelial development, and results indicate that p63 is critical for maintaining the progenitor-cell populations that are necessary to sustain epithelialDevelopment and morphogenesis.
2.3K
p63, a p53 homolog at 3q27-29, encodes multiple products with transactivating, death-inducing, and dominant-negative activities.
Annie Yang,Mourad Kaghad,Yunmei Wang,Emily Gillett,Mark D. Fleming,Mark D. Fleming,Mark D. Fleming,Volker Dötsch,Nancy C. Andrews,Nancy C. Andrews,Daniel Caput,Frank McKeon +11 more
TL;DR: The cloning of p63, a gene at chromosome 3q27-29 that bears strong homology to the tumor suppressor p53 and to the related gene, p73, is described and the possibility of physiological interactions among members of the p53 family is suggested.
2.2K
The p53 pathway: positive and negative feedback loops
TL;DR: The p53 pathway responds to stresses that can disrupt the fidelity of DNA replication and cell division by activation of the p53 protein as a transcription factor that initiates a program of cell cycle arrest, cellular senescence or apoptosis.
2.1K