Vo Thanh-Trang, Letai Anthony
Anthony Letai-Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Adv Exp Med Biol. 2010;687:49-63. doi: 10.1007/978-1-4419-6706-0_3.
Apoptosis, a form of cellular suicide is a key mechanism involved in the clearance of cells that are dysfunctional, superfluous or infected. For this reason, the cell needs mechanisms o sense death cues and relay death signals to the apoptotic machinery involved in cellular execution. In the intrinsic apoptotic pathway, a subclass of BCL-2 family proteins called the BH3-onlyproteins are responsible for triggering apoptosis in response to varied cellular stress cues. The mechanisms by which they are regulated are tied to the type of cellular stress they sense. Once triggered, they interact with other BCL-2 family proteins to cause mitochondrial outer membrane permeabilization which in turn results in the activation ofserine proteases necessary for cell killing. Failure to properly sense death cues and relay the death signal can have a major impact on cancer. This chapter will discuss our current models of how BH3-only proteins function as well as their impact on carcinogenesis and cancer treatment.
细胞凋亡是一种细胞自杀形式，是清除功能失调、多余或受感染细胞的关键机制。因此，细胞需要具备感知死亡信号并将死亡信号传递给参与细胞凋亡执行机制的能力。在内在凋亡途径中，一类名为仅含BH3结构域蛋白的BCL-2家族蛋白负责响应各种细胞应激信号触发细胞凋亡。它们的调控机制与所感知的细胞应激类型相关。一旦被触发，它们会与其他BCL-2家族蛋白相互作用，导致线粒体外膜通透性增加，进而激活细胞死亡所需的丝氨酸蛋白酶。无法正确感知死亡信号并传递死亡信号会对癌症产生重大影响。本章将讨论我们目前关于仅含BH3结构域蛋白如何发挥作用及其对肿瘤发生和癌症治疗影响的模型。
