p53 homologue, p51/p63, controls keratinocyte proliferation/differentiation due to Notch activity

P53同源基因p51/p63主要在角质形成干细胞中表达，对表皮的形成是必不可少的。NOTCH1是另一个在这一过程中不可或缺的基因，它可以诱导角质形成细胞的生长停滞和分化。我们发现p51的一种异构体ΔNp51B(ΔNp63α)的外源表达通过抑制p21的表达和维持整合素的表达来阻断Notch1依赖的小鼠角质形成细胞的生长停滞和分化。此外，ΔNp51B本身还能诱导整合素α6β4的表达，从而促进基底层细胞与基底膜的附着，从而使细胞保持在未成熟状态。因此，我们得出结论，即使在Notch1的影响下，Notch1 Np51B的表达也保证了整合素的表达，并且ΔNp51B是一个长期寻找的因子，需要通过抑制Δ活性来维持基底细胞角质形成细胞的不成熟。我们将假设一个合理的模型，解释鳞状上皮结构的维持，并为皮肤病的病理特征提供机制解释，包括癌症、牛皮癣以及生理性伤口愈合。

p53 homologue, p51/ p63, predominantly expressed in keratinocyte stem cells, is indispensable for the formation of epidermis. Notch1, another such gene indispensable for the process, induces growth arrest and differentiation in keratinocytes. We found that exogenous expression of ΔNp51B (ΔNp63α), one of the isoforms of p51 specifically expressed in basal keratinocytes, blocked Notch 1 dependent growth arrest and differentiation in mouse keratinocytes by inhibiting p21 expression and maintaining integrins expression. Furthermore, ΔNp51B by itself was found to have ability to induce expression of integrin α6β4, which promotes attachment of basal cells to basal membrane thereby keeping the cells in immature state. Therefore, we conclude that ΔNp51B expression warrants integrin expression even under the influence of Notch1 and that ΔNp51B is a long-sought factor required to maintain basal cell keratinocytes immaturity by inhibiting Notch activity. We will postulate a plausible model explaining the maintenance of the squamous epithelium architectures as well as offering mechanistic explanations for pathological features of skin diseases, including cancers, psoriasis along with physiological wound healings.