Molecular Oncology, Department of Hematology, Oncology and Immunology, Institute of Molecular Biology and Tumor Research, Philipps-University Marburg, Marburg, Germany.
Cancer Lett. 2013 May 28;332(2):229-36. doi: 10.1016/j.canlet.2011.07.030. Epub 2011 Aug 22.
p73 is a member of the p53 family of tumor suppressors. Transactivating isoforms of p73 (TAp73) have p53-like, anti-proliferative and pro-apoptotic activities that are crucial for an efficient chemotherapy response. In line with this, genetic studies in mice have confirmed that TAp73 acts as a tumor suppressor. However, in contrast to p53, which is commonly inactivated in human cancer by point mutations, the TP73 gene is almost never mutated. Instead, the tumor suppressor activity of TAp73 is inhibited through a variety of mechanisms including epigenetic silencing and complex formation with inhibitory proteins. All these mechanisms have in common that they are in principle reversible and therefore amenable to therapeutic intervention. Here, we will review how tumor cells control the tumor suppressor activity of TAp73 and discuss possible strategies targeting p73 for reactivation.
p73 是 p53 肿瘤抑制因子家族的一员。p73 的转录激活异构体（TAp73）具有 p53 样的抗增殖和促凋亡活性，这对于有效的化疗反应至关重要。与此一致，在小鼠中的遗传研究证实 TAp73 作为一种肿瘤抑制因子发挥作用。然而，与 p53 不同，p53 通常通过点突变在人类癌症中失活，TP73 基因几乎从不发生突变。相反，TAp73 的肿瘤抑制活性通过多种机制受到抑制，包括表观遗传沉默和与抑制蛋白形成复合物。所有这些机制的共同点是它们在原则上是可逆的，因此可以进行治疗干预。在这里，我们将回顾肿瘤细胞如何控制 TAp73 的肿瘤抑制活性，并讨论针对 p73 进行重新激活的可能策略。
