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Targeting p73 in cancer

机译：在癌症中靶向p73

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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.
机译：p73是p53家族抑癌基因的成员。 p73（TAp73）的反式同工型具有p53样，抗增殖和促凋亡活性，这对于有效的化学疗法反应至关重要。与此相一致，在小鼠中进行的遗传研究已经证实TAp73可以作为肿瘤抑制因子。但是，与p53相比，后者在人类癌症中通常会因点突变而失活，而TP73基因几乎从未突变。相反，TAp73的肿瘤抑制活性是通过多种机制抑制的，包括表观遗传沉默和与抑制蛋白的复合物形成。所有这些机制的共同点是，它们在原则上是可逆的，因此可以接受治疗干预。在这里，我们将回顾肿瘤细胞如何控制TAp73的抑癌活性，并讨论针对p73进行重新激活的可能策略。

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