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p53家族及其通路相关蛋白在女性生殖中的新功能

[The new function of p53 family and its pathway related proteins in female reproduction].

作者信息

Zhu Hui, Li An, Yu Jian-Hua, Xiang Chao-Jie, Su Shi-Da, Huang Lei, Fang Yu-Jie, Luo Ying, Tang Wen-Ru

机构信息

Laboratory of Molecular Genetics of Aging and Tumor, Kunming University of Science and Technology, Kunming, China.

出版信息

Yi Chuan. 2012 Aug;34(8):943-9. doi: 10.3724/sp.j.1005.2012.00943.

Abstract

p53 is an important tumor suppressor gene and one of the key genes in sensing and regulating responses to the environmental stress. Recent study showed that cold winter temperature naturally selected p53 Arg72 in eastern Asian population, suggesting that p53 plays a role in reproduction. It has also been reported that some SNPs of p53, Mdm2(Murine double minute 2), MdmX and Hausp (Herpes virus-associated ubiquitin-specific protease) in p53 pathway are associated with the risk of the women's reproduction disorder. p53 regulates the LIF (leukaemia inhibitory factor) expression level by its DBD domain, and thus contributes to female reproduction by affecting the embryo implantation process. The MDM2, MDMX, and HAUSP proteins regulates the level and activity of p53 protein, which are critical for the appropriate p53 response in the embryo implantation process. The members of p53 family, p63 and p73, also play roles in female reproduction through other pathways. p63 has been implicated as a major regulator of oocyte death following treatment with irradiation and chemotherapeutic drugs, which prevents fetal malformation. p73 regulates the formation of spindle assembly complex(SAC). The dysfunction of SAC results in poor blastocyst quality and defects in kinetochore-microtubule associations, which leads to aneuploidy. This review summarized the function of p53 family and its pathway related proteins in female reproduction, pointed out a new method in improving the success rate in IVF-ET, and provided a new diagnosis idea for unexplained infertile women. It will facilitate personalized strategies in the infertility therapy.

摘要

p53是一种重要的肿瘤抑制基因,也是感知和调节对环境应激反应的关键基因之一。最近的研究表明,寒冷的冬季温度在东亚人群中对p53 Arg72进行了自然选择,这表明p53在生殖中发挥作用。也有报道称,p53信号通路中的一些p53、Mdm2(小鼠双微体2)、MdmX和Hausp(疱疹病毒相关泛素特异性蛋白酶)单核苷酸多态性与女性生殖障碍风险相关。p53通过其DBD结构域调节白血病抑制因子(LIF)的表达水平,从而通过影响胚胎着床过程对女性生殖产生影响。MDM2、MDMX和HAUSP蛋白调节p53蛋白的水平和活性,这对于胚胎着床过程中适当的p53反应至关重要。p53家族成员p63和p73也通过其他途径在女性生殖中发挥作用。p63被认为是辐射和化疗药物处理后卵母细胞死亡的主要调节因子,可预防胎儿畸形。p73调节纺锤体组装复合物(SAC)的形成。SAC功能障碍导致囊胚质量差和动粒-微管连接缺陷,从而导致非整倍体。本文综述了p53家族及其信号通路相关蛋白在女性生殖中的作用,指出了提高体外受精-胚胎移植成功率的新方法,并为不明原因不孕女性提供了新的诊断思路。这将有助于不孕治疗的个性化策略。

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