King Kathryn E, Weinberg Wendy C
Laboratory of Immunobiology, Division of Monoclonal Antibodies, FDA Center for Drug Evaluation and Research, Bethesda, Maryland 20892, USA.
Mol Carcinog. 2007 Aug;46(8):716-24. doi: 10.1002/mc.20337.
p63 is a member of a gene family also including the p53 tumor suppressor and p73. In contrast to p53, p63 is rarely mutated in human cancers. Rather, gene amplification and dysregulated expression of p63 protein have been observed, particularly in squamous cell carcinomas. p63 is essential for development of stratified squamous epithelium, including the epidermis. The p63 gene is expressed as multiple protein isoforms with different functional capacities, and the balance of these isoforms, along with the presence or absence of the other family members, p53 and p73, can impact biological outcome. Both gene silencing and overexpression approaches have been utilized to elucidate the contributions of specific p63 isoforms to normal epidermal morphogenesis and tissue maintenance. While numerous studies have established the essential nature of p63 in the epidermis, the basis of this requirement, and the unique, as well as, overlapping functions of the individual isoforms, remain controversial. In this review, we summarize the current understanding of roles played by specific p63 isoforms within the context of epidermal morphogenesis and homeostasis of the established epidermis, and the potential impact of p63 dysregulation on cancer development.
p63是一个基因家族的成员，该家族还包括p53肿瘤抑制因子和p73。与p53不同，p63在人类癌症中很少发生突变。相反，已观察到p63基因扩增和p63蛋白表达失调，尤其是在鳞状细胞癌中。p63对于包括表皮在内的复层鳞状上皮的发育至关重要。p63基因表达为具有不同功能能力的多种蛋白质异构体，这些异构体的平衡，以及其他家族成员p53和p73的存在与否，均可影响生物学结果。基因沉默和过表达方法均已用于阐明特定p63异构体对正常表皮形态发生和组织维持的作用。虽然众多研究已证实p63在表皮中的重要性质，但其需求的基础以及各个异构体独特和重叠的功能仍存在争议。在本综述中，我们总结了目前对特定p63异构体在表皮形态发生和成熟表皮稳态中的作用，以及p63失调对癌症发展潜在影响的理解。
