Boise L H, Gottschalk A R, Quintáns J, Thompson C B
Gwen Knapp Center for Lupus and Immunology Research, University of Chicago, IL 60637, USA.
Curr Top Microbiol Immunol. 1995;200:107-21. doi: 10.1007/978-3-642-79437-7_8.
In this review we have discussed the importance of Bcl-2 and related proteins in the regulation of apoptotic cell death in mammalian systems. It is clear that Bcl-2 plays a critical role in controlling many forms of PCD. Bcl-2 seems to have particular significance in lymphocyte development and the function of the immune system. We have also discussed the increasing size of the newly identified Bcl-2 family. There are a number of Bcl-2 homologues in human, murine, avian, nematode, and viral systems. The evolutionary conservation of the function of the Bcl-2 homologues, reinforces the importance of PCD in all complex organisms. Some of these bcl-2-like genes function as agonists and others as antagonists. Despite the seemingly universal importance of Bcl-2, it is unable to prevent PCD in all systems. In addition, we have described a role for other Bcl-2 family members in systems in which Bcl-2 is ineffective and supplied a potential rationale for the large number of genes involved in the regulation of PCD. Identification and functional analysis of the Bcl-2 family members reveals the complex nature of cell death regulation. As we begin to appreciate the significance of PCD in the control of development and homeostasis, its regulation at the molecular level is becoming better understood. Bcl-2 has long been the only known intracellular regulator of the PCD pathway(s), although its ability to prevent apoptosis is not universal. We now know that bcl-2 is only one member of an evolutionary conserved family of genes which display different patterns of expression as well as function. At least two family members, Bcl-xs and Bax, act in opposition to Bcl-2. The discovery of these new family members, including those with Bcl-2-like function and antagonists, should help clear up the discrepancies seen in Bcl-2's ability to protect cells from PCD. In doing so, we will be able to further define the pathways associated with cell death signaling. The study of these family members, as well as the non-related genes of the PCD pathways (ced-3, ced-4, ice) should lead us to understanding of how cells of multicellular organisms make decisions to die.
在本综述中，我们讨论了Bcl-2及相关蛋白在哺乳动物系统中调控凋亡性细胞死亡的重要性。显然，Bcl-2在控制多种形式的程序性细胞死亡中起着关键作用。Bcl-2在淋巴细胞发育和免疫系统功能中似乎具有特殊意义。我们还讨论了新发现的Bcl-2家族规模不断扩大的情况。在人类、小鼠、禽类、线虫和病毒系统中存在许多Bcl-2同源物。Bcl-2同源物功能的进化保守性，强化了程序性细胞死亡在所有复杂生物体中的重要性。这些bcl-2样基因中的一些起激动剂作用，另一些起拮抗剂作用。尽管Bcl-2看似具有普遍重要性，但它无法在所有系统中阻止程序性细胞死亡。此外，我们描述了其他Bcl-2家族成员在Bcl-2无效的系统中的作用，并为参与程序性细胞死亡调控的大量基因提供了潜在的理论依据。对Bcl-2家族成员的鉴定和功能分析揭示了细胞死亡调控的复杂性。随着我们开始认识到程序性细胞死亡在发育和体内平衡控制中的重要性，其在分子水平上的调控也越来越被理解。长期以来，Bcl-2一直是程序性细胞死亡途径唯一已知的细胞内调节因子，尽管其阻止细胞凋亡的能力并不普遍。我们现在知道，bcl-2只是一个进化保守基因家族的成员之一，这些基因表现出不同的表达模式和功能。至少有两个家族成员，Bcl-xs和Bax，其作用与Bcl-2相反。这些新家族成员的发现，包括那些具有Bcl-2样功能和拮抗剂的成员，应该有助于消除在Bcl-2保护细胞免受程序性细胞死亡能力方面所看到的差异。这样做，我们将能够进一步确定与细胞死亡信号传导相关的途径。对这些家族成员以及程序性细胞死亡途径的非相关基因（ced-3、ced-4、ice）的研究，应该会使我们了解多细胞生物体的细胞如何做出死亡决定。
