Department of Pediatric Oncology and the Program in Cancer Chemical Biology, Dana-Farber Cancer Institute, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA.
Trends Biochem Sci. 2011 Dec;36(12):642-52. doi: 10.1016/j.tibs.2011.08.009. Epub 2011 Oct 4.
BAX, the BCL-2-associated X protein, is a cardinal proapoptotic member of the BCL-2 family, which regulates the critical balance between cellular life and death. Because so many medical conditions can be categorized as diseases of either too many or too few cells, dissecting the biochemistry of BCL-2 family proteins and developing pharmacological strategies to target them have become high priority scientific objectives. Here, we focus on BAX, a latent, cytosolic and monomeric protein that transforms into a lethal mitochondrial oligomer in response to cellular stress. New insights into the structural location of BAX's 'on switch', and the multi-step conformational changes that ensue upon BAX activation, are providing fresh opportunities to modulate BAX for potential benefit in human diseases characterized by pathologic cell survival or unwanted cellular demise.
BAX（BCL-2 相关 X 蛋白）是 BCL-2 家族中的主要促凋亡成员，它调节细胞生死之间的关键平衡。由于许多医学病症都可以归类为细胞过多或过少的疾病，因此剖析 BCL-2 家族蛋白的生物化学特性并开发针对它们的药物策略已成为高度优先的科学目标。在这里，我们重点介绍 BAX，它是一种潜在的、细胞质和单体蛋白，在细胞应激时转化为致命的线粒体寡聚体。BAX 的“开启开关”的结构位置以及 BAX 激活后随之发生的多步构象变化的新见解，为调节 BAX 以在病理性细胞存活或不需要的细胞死亡为特征的人类疾病中带来潜在益处提供了新的机会。
