Chittenden T, Harrington E A, O'Connor R, Flemington C, Lutz R J, Evan G I, Guild B C
Apoptosis Technology Inc., Cambridge, Massachusetts 02139, USA.
Nature. 1995 Apr 20;374(6524):733-6. doi: 10.1038/374733a0.
Cells are eliminated in a variety of physiological settings by apoptosis, a genetically encoded process of cellular suicide. Apoptosis comprises an intrinsic cellular defence against tumorigenesis, which, when suppressed, may contribute to the development of malignancies. The bcl-2 oncogene, which is activated in follicular lymphomas, functions as a potent suppressor of apoptosis under diverse conditions. Here we describe the complementary DNA cloning and functional analysis of a new Bcl-2 homologue, Bak, which promotes cell death and counteracts the protection from apoptosis provided by Bcl-2. Moreover, enforced expression of Bak induces rapid and extensive apoptosis of serum-deprived fibroblasts. This raises the possibility that Bak is directly involved in activating the cell death machinery.
在多种生理环境中，细胞通过凋亡被清除，凋亡是一种由基因编码的细胞自杀过程。凋亡构成了细胞对抗肿瘤发生的内在防御机制，这种防御机制一旦受到抑制，可能会促使恶性肿瘤的发展。在滤泡性淋巴瘤中被激活的bcl - 2癌基因，在多种条件下作为凋亡的有效抑制因子发挥作用。在此，我们描述了一种新的Bcl - 2同源物Bak的互补DNA克隆及功能分析，Bak可促进细胞死亡，并对抗Bcl - 2提供的抗凋亡保护作用。此外，强制表达Bak可诱导血清剥夺的成纤维细胞迅速且广泛地凋亡。这增加了Bak直接参与激活细胞死亡机制的可能性。
