Linette G P, Li Y, Roth K, Korsmeyer S J
Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, MO 63110, USA.
Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9545-52. doi: 10.1073/pnas.93.18.9545.
BCL-2-deficient T cells demonstrate accelerated cell cycle progression and increased apoptosis following activation. Increasing the levels of BCL-2 retarded the G0-->S transition, sustained the levels of cyclin-dependent kinase inhibitor p27Kip1, and repressed postactivation death. Proximal signal transduction events and immediate early gene transcription were unaffected. However, the transcription and synthesis of interleukin 2 and other delayed early cytokines were markedly attenuated by BCL-2. In contrast, a cysteine protease inhibitor that also blocks apoptosis had no substantial affect upon cytokine production. InterleUkin 2 expression requires several transcription factors of which nuclear translocation of NFAT (nuclear factor of activated T cells) and NFAT-mediated transactivation were impaired by BCL-2. Thus, select genetic aberrations in the apoptotic pathway reveal a cell autonomous coregulation of activation.
BCL-2缺陷型T细胞在激活后显示出加速的细胞周期进程和增加的细胞凋亡。增加BCL-2的水平会延迟G0期到S期的转变，维持细胞周期蛋白依赖性激酶抑制剂p27Kip1的水平，并抑制激活后的死亡。近端信号转导事件和立即早期基因转录不受影响。然而，BCL-2显著减弱了白细胞介素2和其他延迟早期细胞因子的转录和合成。相比之下，一种同样能阻断细胞凋亡的半胱氨酸蛋白酶抑制剂对细胞因子的产生没有实质性影响。白细胞介素2的表达需要几种转录因子，其中NFAT（活化T细胞核因子）的核转位和NFAT介导的反式激活受到BCL-2的损害。因此，凋亡途径中的特定基因异常揭示了激活的细胞自主共调节。
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