《自然》：p53的正常功能

lepion

p53的正常功能

转录因子p53作为一种肿瘤抑制因子已经受到广泛研究，但人们对其正常生理作用却知之甚少。现在，用小鼠所做的一项研究将p53的正常功能与繁殖和生育联系了起来。p53缺乏导致雌性小鼠胚胎着床较差、受孕率较低和后代身材较小。p53是通过调控LIF来发挥这一功能的。 LIF是一种细胞因子，参与囊胚的着床。这项工作让我们看到这样一个可能性：p53的正常功能对于着床的成功很重要，尤其是对经历体外授精或胚胎转移的妇女来说；同时这一结果也让我们看到了提高习惯性着床失败妇女的着床效率的一个潜在策略。

P53 Regulates Maternal Reproduction through LIF

Extensive studies have shown that p53 is important in tumour prevention. However, little is known about its normal physiological function. Here the authors show that p53 is important in reproduction, in a gender-specific manner. Significant decreases in embryonic implantation, pregnancy rate and litter size were observed in matings with p53-/- female mice but not with p53-/- male mice. The gene encoding leukaemia inhibitory factor (LIF), a cytokine critical for implantation, was identified as a p53-regulated gene that functions as the downstream mediator of this effect. p53 can regulate both basal and inducible transcription of LIF. Loss of p53 decreased both the level and function of LIF in uteri. Lower LIF levels were observed in the uteri of p53-/- mice than in those of p53+/+ mice,
particularly at day 4 of pregnancy, when transiently induced high levels of LIF were crucial for embryonic implantation. This observation probably accounts for the impaired implantation of embryos in p53-/- female mice. Administration of LIF to pregnant p53-/- mice restored maternal reproduction by improving implantation. These results demonstrate a function for p53 in maternal reproduction through the regulation of LIF. Evidence is accumulating that p53 may have a similar function in humans.

来自Nature杂志
http://www.nature.com/nature/jou ... ll/nature05993.html