用siRNA研究p53兄弟

p63是多异构体p53家族的一个成员，是表皮发育必须的。p63在最初的表皮细胞分化或以干细胞为基础的自我更新过程中的功能都是有差异的。

为了分析p63在发育后背景下的功能，来自美国斯坦福大学医学院的研究人员利用siRNA直接靶向p63来下调再生的人类表皮中的p63表达。p63的丧失导致严重的组织发育不全，并且同时抑制了细胞的分层和分化。

尽管缺失p63的细胞表现出了高的增殖特征，但是分化的缺陷则不是因为组织的发育不全。当研究人员同时敲除p63和p53时，只能挽救因p63敲除产生的细胞增殖缺陷而部分恢复细胞的分化——这意味着表皮增殖和分化中的缺陷是通过p53以来型和非依赖型系统来介导的。

而且，尽管Tap63异构体可能促进后期的分化，但 Np63异构体则是p63的主要作用因子。

部分英文原文：

p63 and the epithelial stem cell: more than status quo?

The discovery of p63, the most ancient member of the p53 family (for review, see Yang et al. 2002), was soon followed by back-to-back reports of a remarkable phenotype of mice lacking this gene: They die perinatally due to the absence of a large number of epithelial structures including skin, breast, prostate, and urothelia, among others (Mills et al. 1999; Yang et al. 1999). Despite the
contemporaneous nature of these publications, they expressed profound disagreement regarding the function of p63, as reflected in the mouse mutants. Mills et al. (1999) argued that p63 was essential for the commitment of a simple ectoderm to epidermal lineages, whereas Yang et
al. (1999) argued that commitment and differentiation of the ectoderm were essentially intact in these mice, and that what was defective was the “proliferative potential”of the epithelial stem cells .Principals from the first group have now addressed this problem from fundamentally different angles and have proposed new and unexpected functions of the p63 gene in epithelial commitment, maintenance, and differentiation (Koster et al. 2004).

更多原文链接：http://www.genesdev.org/cgi/reprint/18/5/465.pdf