p63是多異構(gòu)體p53家族的一個成員,，是表皮發(fā)育必須的,。p63在最初的表皮細(xì)胞分化或以干細(xì)胞為基礎(chǔ)的自我更新過程中的功能都是有差異的,。
為了分析p63在發(fā)育后背景下的功能，來自美國斯坦福大學(xué)醫(yī)學(xué)院的研究人員利用siRNA直接靶向p63來下調(diào)再生的人類表皮中的p63表達(dá),。p63的喪失導(dǎo)致嚴(yán)重的組織發(fā)育不全,，并且同時抑制了細(xì)胞的分層和分化。
盡管缺失p63的細(xì)胞表現(xiàn)出了高的增殖特征，但是分化的缺陷則不是因為組織的發(fā)育不全,。當(dāng)研究人員同時敲除p63和p53時,，只能挽救因p63敲除產(chǎn)生的細(xì)胞增殖缺陷而部分恢復(fù)細(xì)胞的分化——這意味著表皮增殖和分化中的缺陷是通過p53以來型和非依賴型系統(tǒng)來介導(dǎo)的。
而且,，盡管Tap63異構(gòu)體可能促進(jìn)后期的分化,，但 Np63異構(gòu)體則是p63的主要作用因子。
這些研究數(shù)據(jù)表明,，p63是發(fā)育成熟的增殖和分化成角化細(xì)胞所必須的,。研究的結(jié)果發(fā)表在11月14日的《Gene and Development》雜志上，并且成為封面故事,。
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).
更多原文鏈接：http://www.genesdev.org/cgi/reprint/18/5/465.pdf
