文章：

CHK2激酶：癌症易感性和癌症治疗——同一枚硬币的两面？

CHK2 kinase: cancer susceptibility and cancer therapy – two sides of the same coin?

原文发布日期：2007-12-01

DOI: 10.1038/nrc2251

类型: Review Article

开放获取: 否

要点：

1. CHK2 is a versatile and multifunctional kinase that regulates the cell's response to DNA damage by phosphorylating a number of distinct cellular substrates.
2. CHK2 can prevent tumour progression by averting genomic instability through DNA repair and, if this is not possible, by causing the cell to senesce or die.
3. Human genetic studies clearly show that CHEK2 is a multiorgan tumour susceptibility gene, but current evidence indicates that CHEK2 on its own does not predispose to cancer.
4. A potential therapeutic approach in patients whose tumours harbour CHEK2 mutations may be treatment with inhibitors of other proteins that are involved in DNA-repair pathways, inactivation of which may be lethal in combination with a loss of CHEK2.
5. Looking at the other side of the coin, in cancer patients with a functional CHK2 protein a key issue is defining how this kinase manages to elicit distinct cellular outcomes such as cell survival through DNA repair versus apoptosis or senescence.

要点翻译：

1. CHK2是一种多功能激酶，通过磷酸化多种细胞底物来调节细胞对DNA损伤的反应。
2. 它能够通过DNA修复来避免基因组不稳定性，若修复无法实现则促使细胞衰老或死亡，从而阻止肿瘤进展。
3. 人类遗传学研究明确显示CHEK2是一种多器官肿瘤易感基因，但现有证据表明CHEK2本身并不直接导致癌症易感性。
4. 对于携带CHEK2突变肿瘤患者，一种潜在治疗策略是使用DNA修复通路中其他蛋白的抑制剂，这些蛋白的失活与CHEK2缺失共同作用可能引发细胞死亡。
5. 另一方面，对于具有功能性CHK2蛋白的癌症患者，关键问题在于阐明该激酶如何调控不同的细胞命运——是通过DNA修复实现细胞存活，还是走向凋亡或衰老。

英文摘要：

In the past decade, CHK2 has emerged as an important multifunctional player in the DNA-damage response signalling pathway. Parallel studies of the human CHEK2 gene have also highlighted its role as a candidate multiorgan tumour susceptibility gene rather than a highly penetrant predisposition gene for Li–Fraumeni syndrome. As discussed here, our current understanding of CHK2 function in tumour cells, in both a biological and genetic context, suggests that targeted modulation of the active kinase or exploitation of its loss in tumours could prove to be effective anti-cancer strategies.

摘要翻译： 

在过去十年中，CHK2已成为DNA损伤反应信号通路中一个重要的多功能参与者。对人类CHEK2基因的并行研究也强调了其作为候选多器官肿瘤易感基因的作用，而非李-佛美尼综合征的高外显率易感基因。正如本文所讨论的，我们目前对CHK2在肿瘤细胞中功能的理解，无论从生物学还是遗传学背景来看，都表明靶向调控其活性激酶或利用其在肿瘤中的缺失，可能成为有效的抗癌策略。

原文链接：

CHK2 kinase: cancer susceptibility and cancer therapy – two sides of the same coin?