Wang H G, Reed J C
Burnham Institute, Program on Apoptosis & Cell Death Research, La Jolla, CA 92037, USA.
Histol Histopathol. 1998 Apr;13(2):521-30. doi: 10.14670/HH-13.521.
The Bcl-2 protein blocks a distal step in an evolutionarily conserved pathway for programmed cell death and apoptosis. The gene encoding this protein was first discovered because of its involvement in the t(14;18) chromosomal translocations commonly found in B-cell lymphomas. Overexpression of Bcl-2 also occurs in many other types of human cancers, and prevents cell death induced by nearly all anticancer drugs and radiation. Since the discovery of Bcl-2 over ten years ago, several cellular and viral homologs have been identified, some of which suppress cell death and others which promote apoptosis. Many of these proteins can interact with each other through a complex network of homo- and heterodimers. Though functionally important, dimerization events still do not explain in a broader sense how these proteins actually control cell life and death. Recent findings that Bcl-2 can function both as an ion channel and as an adapter or docking protein however are beginning to provide insights into the molecular mechanisms through which these proteins regulate the programmed cell death pathway in normalcy and disease.
Bcl-2蛋白在进化保守的程序性细胞死亡和凋亡途径中阻断一个远端步骤。编码该蛋白的基因最初是因其参与B细胞淋巴瘤中常见的t(14;18)染色体易位而被发现的。Bcl-2的过表达也发生在许多其他类型的人类癌症中，并能阻止几乎所有抗癌药物和辐射诱导的细胞死亡。自十多年前发现Bcl-2以来，已鉴定出几种细胞和病毒同源物，其中一些抑制细胞死亡，另一些则促进凋亡。这些蛋白中的许多可以通过同二聚体和异二聚体的复杂网络相互作用。虽然二聚化事件在功能上很重要，但从更广泛的意义上讲，它仍然无法解释这些蛋白实际上是如何控制细胞生死的。然而，最近的研究发现Bcl-2既可以作为离子通道发挥作用，也可以作为衔接蛋白或停靠蛋白，这开始为这些蛋白在正常和疾病状态下调节程序性细胞死亡途径的分子机制提供了见解。
