Kouwenhoven Evelyn N, van Bokhoven Hans, Zhou Huiqing
Radboud University, Department of Molecular Developmental Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.
Radboud university medical center, Department of Human Genetics, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.
Biochim Biophys Acta. 2015 Jun;1849(6):590-600. doi: 10.1016/j.bbagrm.2015.03.003. Epub 2015 Mar 19.
The transcription factor p63 belongs to the p53 family and is a key regulator in epithelial commitment and development. Mutations in p63 give rise to several epithelial related disorders with defects in skin, limb and orofacial structures. Since the discovery of p63, efforts have been made to identify its target genes using individual gene approaches and to understand p63 function in normal epithelial development and related diseases. Recent genome-wide approaches have identified tens of thousands of potential p63-regulated target genes and regulatory elements, and reshaped the concept of gene regulation orchestrated by p63. These data also provide insights into p63-related disease mechanisms. In this review, we discuss the regulatory role of p63 in normal and diseased epithelial development in light of these novel findings. We also propose future perspectives for dissecting the molecular mechanism of p63-mediated epithelial development and related disorders as well as for potential therapeutic strategies.
转录因子p63属于p53家族，是上皮细胞定向分化和发育过程中的关键调节因子。p63基因的突变会引发多种与上皮组织相关的疾病，这些疾病在皮肤、四肢和口腔面部结构方面存在缺陷。自p63被发现以来，人们一直致力于通过单个基因研究方法来确定其靶基因，并了解p63在正常上皮发育及相关疾病中的功能。最近的全基因组研究方法已经鉴定出了数以万计潜在的p63调控靶基因和调控元件，重塑了由p63精心编排的基因调控概念。这些数据也为深入了解与p63相关的疾病机制提供了线索。在这篇综述中，我们将根据这些新发现讨论p63在正常和患病上皮发育中的调控作用。我们还提出了未来的研究方向，以剖析p63介导的上皮发育和相关疾病的分子机制，以及潜在的治疗策略。
