Romano Rose-Anne, Sinha Satrajit
Department of Biochemistry, Center for Excellence in Bioinformatics and Life Sciences, State University of New York at Buffalo, Buffalo, NY 14203, USA.
Indian J Exp Biol. 2011 Oct;49(10):721-31.
Skin keratinocytes form a tightly knit and layered epithelium at the surface of the body protecting the body from the outside environment. The formation and maintenance of skin epidermis is governed by dynamic and well-coordinated processes of cell proliferation, differentiation, and self-renewal. Such important cell fate decisions are made possible in part by transcription factors, which activate and repress unique sets of genes in a temporal and spatial pattern. The Tp63 gene encodes for multiple isoforms for one such transcription factor that serves as a key regulator of epidermal development and differentiation. The crucial function of p63 is epitomized by the phenotype of p63 knockout mice--in the absence of p63, there is a profound block in the development of skin epidermis and all related appendages such as hair follicles. Human syndromes resulting from Tp63 gene mutations phenocopy the p63 knockout phenotype, highlighting the evolutionarily conserved function of this factor in epithelial biology. Although the function of p63 as an important hub in transcriptional and signaling networks of keratinocytes is well established, the underlying molecular mechanisms of p63 action is continually redefined with the development of new genetic models and more extensive biochemical analysis. In this review the biological role of deltaNp63, the predominant isoform that is expressed in skin keratinocytes has been described. Results from transgenic animal models that have shed new information on the function of deltaNp63 in the epidermis and hair follicles have been discussed. Further, the molecular mechanisms that maintain the fine-tuned expression of deltaNp63 in skin keratinocytes are also described.
皮肤角质形成细胞在身体表面形成紧密相连的分层上皮组织，保护身体免受外界环境的侵害。皮肤表皮的形成和维持受细胞增殖、分化和自我更新等动态且协调良好的过程所调控。这些重要的细胞命运决定部分是由转录因子实现的，转录因子以时空模式激活和抑制独特的基因集。Tp63基因编码一种这样的转录因子的多种异构体，该转录因子是表皮发育和分化的关键调节因子。p63的关键功能在p63基因敲除小鼠的表型中得到体现——在没有p63的情况下，皮肤表皮和所有相关附属器官（如毛囊）的发育会出现严重阻滞。由Tp63基因突变导致的人类综合征模拟了p63基因敲除的表型，突出了该因子在上皮生物学中进化保守的功能。尽管p63作为角质形成细胞转录和信号网络中的重要枢纽的功能已得到充分确立，但随着新的遗传模型的发展和更广泛的生化分析，p63作用的潜在分子机制不断被重新定义。在这篇综述中，描述了在皮肤角质形成细胞中表达的主要异构体deltaNp63的生物学作用。讨论了转基因动物模型的结果，这些结果为deltaNp63在表皮和毛囊中的功能提供了新信息。此外，还描述了维持皮肤角质形成细胞中deltaNp63微调表达的分子机制。
