Proteomics: a strategy to understand the novel targets in protein misfolding and cancer therapy.
Proteomics: a strategy to understand the novel targets in protein misfolding and cancer therapy.
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DOI：
10.1586/epr.10.70
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发表时间：
2010-08
影响因子：
3.4
通讯作者：
Merchant NB
中科院分区：
文献类型：
--
作者：
Nagaraj NS;Singh OV;Merchant NB
蛋白质在折叠时发挥着重要的功能。蛋白质错误折叠发生在不同的生化过程中，并可能导致以遗传不稳定为特征的癌症等疾病的发展。癌症微环境使恶性细胞暴露于各种可能进一步促进蛋白质错误折叠的应激条件下。肿瘤的发生和发展往往源于干扰肿瘤抑制蛋白和癌基因正常功能的突变。这可能是由于蛋白质催化活性的改变，效应蛋白结合位点的丧失或天然折叠蛋白构象的改变。Src家族激酶、p53、mTOR和HSC70相互作用蛋白（CHIPs）的c端是与蛋白质错误折叠和肿瘤发生相关的一些例子。分子伴侣蛋白，如热休克蛋白（HSP）70和HSP90，协助蛋白质折叠和识别目标错误折叠蛋白降解。癌症中的这种错误折叠很可能与共同的原理有关，因此，可能为确定治疗干预的共同目标提供令人兴奋的可能性。在这里，我们的目的是回顾一些例子，显示如何改变折叠的肿瘤抑制蛋白或致癌基因导致肿瘤发生。讨论了在肿瘤治疗中靶向修复或降解蛋白质错误折叠的可能性。
Proteins carry out important functions as they fold themselves. Protein misfolding occurs during different biochemical processes and may lead to the development of diseases such as cancer, which is characterized by genetic instability. The cancer microenvironment exposes malignant cells to a variety of stressful conditions that may further promote protein misfolding. Tumor development and progression often arises from mutations that interfere with the appropriate function of tumor-suppressor proteins and oncogenes. These may be due to alteration of catalytic activity of the protein, loss of binding sites for effector proteins or alterations of the native folded protein conformation. Src family kinases, p53, mTOR and C-terminus of HSC70 interacting protein (CHIPs) are some examples associated with protein misfolding and tumorigenesis. Molecular chaperones, such as heat-shock protein (HSP)70 and HSP90, assist protein folding and recognize target misfolded proteins for degradation. It is likely that this misfolding in cancer is linked by common principles, and may, therefore, present an exciting possibility to identify common targets for therapeutic intervention. Here we aim to review a number of examples that show how alterations in the folding of tumor-suppressor proteins or oncogenes lead to tumorigenesis. The possibility of targeting the targets to repair or degrade protein misfolding in cancer therapy is discussed.
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