解析细胞程序性死亡的规律以提高癌症和其他疾病的治疗效果。
Deciphering the rules of programmed cell death to improve therapy of cancer and other diseases.
机构信息
The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
出版信息
EMBO J. 2011 Aug 23;30(18):3667-83. doi: 10.1038/emboj.2011.307.
Abstract
Apoptosis, the major form of programmed cell death in metazoan organisms, plays critical roles in normal development, tissue homeostasis and immunity, and its disturbed regulation contributes to many pathological states, including cancer, autoimmunity, infection and degenerative disorders. In vertebrates, it can be triggered either by engagement of 'death receptors' of the tumour necrosis factor receptor family on the cell surface or by diverse intracellular signals that act upon the Bcl-2 protein family, which controls the integrity of the mitochondrial outer membrane through the complex interactions of family members. Both pathways lead to cellular demolition by dedicated proteases termed caspases. This review discusses the groundbreaking experiments from many laboratories that have clarified cell death regulation and galvanised efforts to translate this knowledge into novel therapeutic strategies for the treatment of malignant and perhaps certain autoimmune and infectious diseases.
摘要
细胞凋亡是多细胞生物中程序性细胞死亡的主要形式，在正常发育、组织稳态和免疫中发挥着关键作用，其调节紊乱导致许多病理状态，包括癌症、自身免疫、感染和退行性疾病。在脊椎动物中，它可以通过细胞表面肿瘤坏死因子受体家族的“死亡受体”的参与或通过作用于 Bcl-2 蛋白家族的各种细胞内信号来触发，该家族通过家族成员的复杂相互作用控制线粒体外膜的完整性。这两条途径都通过称为半胱天冬酶的专用蛋白酶导致细胞破坏。这篇综述讨论了来自许多实验室的开创性实验，这些实验阐明了细胞死亡的调控，并激发了将这一知识转化为治疗恶性疾病、也许还有某些自身免疫和感染性疾病的新治疗策略的努力。
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