Apoptosis regulators as targets for cancer therapy
Apoptosis regulators as targets for cancer therapy
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DOI：
10.1007/s12094-007-0103-7
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发表时间：
2007-09-01
影响因子：
3.4
通讯作者：
Fernandez-Luna, J. L.
中科院分区：
文献类型：
--
作者：
Fernandez-Luna, J. L.
细胞凋亡用于清除多余或受损的细胞，其失调可能导致包括癌症在内的许多病理疾病。过去20年的研究揭开了许多控制细胞凋亡的分子机制。细胞是否会因包括DNA损伤剂在内的各种凋亡刺激而死亡，这在很大程度上取决于Bcl-2家族蛋白之间的相互作用。死亡信号通过BH3-Only蛋白传递到Bax和Bak，后者反过来渗透到线粒体外膜，允许释放凋亡因子，从而触发促进细胞死亡的caspase的激活。这些蛋白水解酶受细胞凋亡抑制因子(IAP)家族成员的严格控制。通过细胞死亡受体激活caspase级联也代表了正常细胞和肿瘤细胞中的一条关键的凋亡途径。对这些凋亡调节因子的基础知识为旨在促进肿瘤细胞死亡或增强对凋亡诱导剂的敏感性的新的治疗策略提供了基础。这篇综述集中在这些策略上。
Apoptosis serves to remove excess or damaged cells and its dysregulation may lead to a number of pathological disorders including cancer. Studies during the last 20 years have unravelled much of the molecular mechanisms that control apoptosis. Whether a cell dies in response to diverse apoptotic stimuli, including DNA-damaging agents, is determined largely by interactions between proteins of the Bcl-2 family. A death signal is transmitted through the BH3-only proteins to Bax and Bak which in turn permeabilise the outer mitochondrial membrane allowing the release of apoptogenic factors, which triggers activation of cell-death-promoting caspases. These proteolytic enzymes are tightly controlled by members of the inhibitor of apoptosis (IAP) family. Activation of the caspase cascade via cell death receptors also represents a key apoptotic pathway in both normal and tumour cells. Basic knowledge of these apoptosis regulators provides the basis for novel therapeutic strategies aimed at promoting tumour cell death or enhancing susceptibility to apoptotic inducers. This review focuses on these strategies.