Guerrini Luisa, Costanzo Antonio, Merlo Giorgio R
Department of Biomolecular Science and Biotechnology, University of Milan, 20133 Milano, Italy.
J Biomed Biotechnol. 2011;2011:864904. doi: 10.1155/2011/864904. Epub 2011 May 22.
The p53-related transcription factor p63 is critically important for basic cellular functions during development of the ectoderm and derived structure and tissues, including skin, limb, palate, and hair. On the one side, p63 is required to sustain the proliferation of keratinocyte progenitors, while on the other side it is required for cell stratification, commitment to differentiate, cell adhesion, and epithelial-mesenchymal signaling. Molecules that are components or regulators of the p63 pathway(s) are rapidly being identified, and it comes with no surprise that alterations in the p63 pathway lead to congenital conditions in which the skin and other ectoderm-derived structures are affected. In this paper, we summarize the current knowledge of the molecular and cellular regulations centered on p63, derived from the comprehension of p63-linked human diseases and the corresponding animal models, as well as from cellular models and high-throughput molecular approaches. We point out common themes and features, that allow to speculate on the possible role of p63 downstream events and their potential exploitation in future attempts to correct the congenital defect in preclinical studies.
与p53相关的转录因子p63在外胚层及其衍生结构和组织（包括皮肤、肢体、腭和毛发）的发育过程中对基本细胞功能至关重要。一方面，p63是维持角质形成细胞祖细胞增殖所必需的，而另一方面，它对于细胞分层、分化承诺、细胞黏附和上皮-间充质信号传导也是必需的。p63信号通路的组成成分或调节分子正在迅速被鉴定出来，因此毫不奇怪，p63信号通路的改变会导致皮肤和其他外胚层衍生结构受到影响的先天性疾病。在本文中，我们总结了目前围绕p63的分子和细胞调控知识，这些知识来源于对与p63相关的人类疾病及相应动物模型的理解，以及细胞模型和高通量分子方法。我们指出了共同的主题和特征，这有助于推测p63下游事件的可能作用及其在未来临床前研究中纠正先天性缺陷的潜在应用。
