Regulation of Fertility by the p53 Family Members.
Regulation of Fertility by the p53 Family Members.
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DOI：
10.1177/1947601911408892
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发表时间：
2011-04-01
期刊：
影响因子：
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通讯作者：
Wang, Jiabei
中科院分区：
文献类型：
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作者：
Hu, Wenwei;Zheng, Tongsen;Wang, Jiabei
P53家族成员由3个转录因子P53、P63和P73组成，在进化过程中是保守的。P53家族蛋白参与了许多重要的细胞功能，包括肿瘤抑制(P53和P73)、上皮细胞层的发育(P63)以及中枢神经系统和免疫系统的发育(P73)。对低等生物中类P53蛋白的研究表明，它们的原始功能是维持生殖细胞的基因组完整性，确保忠实的发育和繁殖。在脊椎动物中，P53家族蛋白在生殖过程中保留了这些功能，同时在生殖过程中发展了额外的重要功能，如调节胚胎着床(P53)。P53通过转录调控白血病抑制因子(LIF)调控胚胎着床。P63，尤其是TAp63，是在减数分裂停滞过程中保护雌性生殖细胞保真度的主要调节因子。P73，尤其是TAp73，调节卵巢功能和卵母细胞的质量。雌性小鼠中p53、p63或p73基因的缺失会导致生育力的显著下降。P53家族蛋白在生殖过程中的这些功能为在P53家族基因的一组单核苷酸多态和单倍型中观察到的正向进化选择提供了合理的解释。更好地了解P53家族蛋白在生殖中的功能可能会导致生育治疗的新策略。
The p53 family members, which consist of 3 transcription factors-p53, p63, and p73-are conserved during evolution. The p53 family proteins are involved in many important cellular functions, including tumor suppression (p53 and p73), the development of epithelial cell layers (p63), and the development of central nervous system and immune system (p73). Studies on p53-like proteins in low organisms have demonstrated that their primordial functions are to maintain the genomic integrity of germ cells and ensure faithful development and reproduction. In vertebrates, the p53 family proteins retain these functions in reproduction and at the same time have developed additional important functions in reproduction, such as the regulation of embryonic implantation (p53). p53 regulates embryonic implantation through transcriptional regulation of leukemia inhibitory factor (LIF). p63, in particular TAp63, is a main regulator to protect the fidelity of female germ cells during meiotic arrest. p73, in particular TAp73, regulates the ovary function and the quality of oocytes. Loss of p53, p63, or p73 genes in female mice leads to a significant decrease in fertility. These functions of the p53 family proteins in reproduction provide a plausible explanation for positive evolutionary selection observed in a group of single nucleotide polymorphisms and haplotypes in the p53 family genes. A better understanding of the functions of the p53 family proteins in reproduction may lead to new strategies for fertility treatment.