Gonfloni Stefania, Caputo Valerio, Iannizzotto Valentina
Department of Biology, University of Rome "Tor Vergata", Rome, Italy.
Int J Dev Biol. 2015;59(1-3):87-93. doi: 10.1387/ijdb.150045sg.
TP63 is the most ancient member of the p53 gene family. The p53 family comprises three transcription factors (p53/p63/p73). They share a high degree of homology and similar domain structure. Yet, they can exist as truncated isoforms. Alternative promoters and splicing sites lead to the generation of several molecules. P53/p63/p73 are important to maintain cell homeostasis. P63 and p73 regulate many p53 target genes. This is due to their common structural features. Both proteins may compensate the loss of p53. This is a common event occurring in more than 50% of malignancies. Yet, p63 (or p73) has its own role. Studies from p63-null mice have shown the key role of p63 in embryo development. Several reports have supported the p63 role in epidermal development and in skin homeostasis. P63 involvement in heart development is currently being researched. Recent studies have found p63 to be "the guardian of human reproduction". In addition, p63 has an important, even controversial, role in cancer. Here, we provide a general overview of p63 regulation and activity. We discuss emerging concepts about its role in germ line protection, metabolism and cancer.
TP63是p53基因家族中最古老的成员。p53家族由三种转录因子（p53/p63/p73）组成。它们具有高度的同源性和相似的结构域结构。然而，它们可以以截短的异构体形式存在。可变启动子和剪接位点导致产生几种分子。P53/p63/p73对维持细胞稳态很重要。P63和p73调节许多p53靶基因。这是由于它们共同的结构特征。这两种蛋白质可能补偿p53的缺失。这是在超过50%的恶性肿瘤中发生的常见事件。然而，p63（或p73）有其自身的作用。对p63基因敲除小鼠的研究表明p63在胚胎发育中起关键作用。一些报告支持p63在表皮发育和皮肤稳态中的作用。目前正在研究p63在心脏发育中的作用。最近的研究发现p63是“人类生殖的守护者”。此外，p63在癌症中具有重要作用，甚至存在争议。在这里，我们提供了p63调控和活性的概述。我们讨论了关于其在生殖系保护、代谢和癌症中作用的新观点。
