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靶向 p73--癌症治疗的一种潜在方法。

Targeting p73--a potential approach in cancer treatment.

机构信息

Division of Molecular Medicine, Rudjer Bošković Institute, BijeniĊka 54, 10000 Zagreb, Croatia.

出版信息

Curr Pharm Des. 2011;17(6):591-602. doi: 10.2174/138161211795222621.

Abstract

The p53 family consists of three members: p53, p63 and p73. All three of them have a role in cell cycle arrest and induction of apoptosis. However, despite structural and partly functional similarity, there are striking differences in their functions and each of them has its own and unique identity. All three genes encode multiple variants with opposing functions in cancer development - full length transactivation forms with proapoptotic and antiproliferative functions, and dominant-negative transactivation-deficient forms with anti-apoptotic (oncogenic) functions. The functional interactions between family members are crucial to gain insight and understand their role in cancer biology. The discovery of p53/p73 network could have a major clinical impact in prognostic use and targeted drug design. In the current review we present the recent achievements in p73 research including very complex and sophisticated p73 regulation and response to DNA damage, and functional interactions among family members. We discuss how p73 has affected drug discovery. According to the p73 tumor suppressor function, we outline current aspects of anticancer therapy.

摘要

p53 家族由三个成员组成:p53、p63 和 p73。它们都在细胞周期阻滞和凋亡诱导中发挥作用。然而,尽管结构和部分功能相似,但它们的功能存在显著差异,并且各自具有独特的身份。这三个基因都编码具有相反功能的多种变体,在癌症发展中——具有促凋亡和抗增殖功能的全长反式激活形式,和具有抗凋亡(致癌)功能的显性负性反式激活缺陷形式。家族成员之间的功能相互作用对于深入了解和理解它们在癌症生物学中的作用至关重要。p53/p73 网络的发现可能会对预后应用和靶向药物设计产生重大的临床影响。在本综述中,我们介绍了 p73 研究的最新进展,包括非常复杂和精细的 p73 调控以及对 DNA 损伤的反应,以及家族成员之间的功能相互作用。我们讨论了 p73 如何影响药物发现。根据 p73 肿瘤抑制功能,我们概述了当前癌症治疗的各个方面。

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