Westfall Matthew D, Pietenpol Jennifer A
Department of Biochemistry, Center in Molecular Toxicology, The Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Carcinogenesis. 2004 Jun;25(6):857-64. doi: 10.1093/carcin/bgh148. Epub 2004 Mar 19.
Discovery of the p53 homologs p63 and p73 has brought new excitement to the p53 field. Identification of homologous genes coding for several proteins with similar and antagonistic properties towards p53 has been both intriguing and perplexing. A multitude of properties have been attributed to these new homologs and this review will focus on the biochemical and biological aspects of one family member, p63. Although the most ancient member of the p53 family, p63 is the most recently discovered and the least is known about this family member. Unlike p53, whose protein expression is not readily detectable in epithelial cells unless they are exposed to various stress conditions, p63 is expressed in select epithelial cells at high levels under normal conditions. p63 is highly expressed in embryonic ectoderm and in the nuclei of basal regenerative cells of many epithelial tissues in the adult including skin, breast myoepithelium, oral epithelium, prostate and urothelia. In contrast to the tumor suppressive function of p53, over-expression of select p63 splice variants is observed in many squamous carcinomas suggesting that p63 may act as an oncogene. Undoubtedly, the biochemical and biological activities attributed to p63 over the next several years will be diverse and regulation of the p63 gene and its several protein products complex. The use of various model systems and the study of human disease should continue to lead to rapid advances in our understanding of the role of p63 in development, epithelial cell maintenance and tumorigenesis.
p53 同源物 p63 和 p73 的发现为 p53 领域带来了新的活力。编码几种对 p53 具有相似和拮抗特性的蛋白质的同源基因的鉴定既引人入胜又令人困惑。这些新的同源物具有多种特性，本综述将聚焦于其中一个家族成员 p63 的生化和生物学方面。尽管 p63 是 p53 家族中最古老的成员，但它却是最近才被发现的，而且人们对这个家族成员了解最少。与 p53 不同，p53 的蛋白表达在未暴露于各种应激条件下的上皮细胞中不易检测到，而 p63 在正常条件下在特定的上皮细胞中高水平表达。p63 在胚胎外胚层以及成体许多上皮组织（包括皮肤、乳腺肌上皮、口腔上皮、前列腺和尿路上皮）的基底再生细胞核中高度表达。与 p53 的肿瘤抑制功能相反，在许多鳞状细胞癌中观察到特定 p63 剪接变体的过表达，这表明 p63 可能作为一种癌基因发挥作用。毫无疑问，在未来几年中，归因于 p63 的生化和生物学活性将是多样的，并且 p63 基因及其多种蛋白质产物的调控也很复杂。使用各种模型系统以及对人类疾病的研究应该会继续促使我们在理解 p63 在发育、上皮细胞维持和肿瘤发生中的作用方面取得快速进展。
