Bcl-2 down-regulates the activity of transcription factor NF-kappaB induced upon apoptosis.
Bcl-2 down-regulates the activity of transcription factor NF-kappaB induced upon apoptosis.
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DOI：
10.1083/jcb.134.1.13
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发表时间：
1996-07
期刊：
影响因子：
--
通讯作者：
Schulze-Osthoff K
中科院分区：
文献类型：
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作者：
Grimm S;Bauer MK;Baeuerle PA;Schulze-Osthoff K
在转录因子NF-κ B的许多靶基因中，有p53和c-myc，两者都参与细胞凋亡。这促使我们研究NF-kappaB在这个过程中的作用。我们报告说，NF-κ B是有效激活血清饥饿，导致293细胞凋亡的条件。与Bcl-2类似，NF-κ B p65亚基的反式显性负突变体部分抑制细胞凋亡，表明转录因子直接参与诱导细胞死亡。正如预期的那样，p65突变体抑制kappaB依赖性基因的表达。令人惊讶的是，短暂或稳定过表达的Bcl-2具有相同的效果。这两种蛋白的转录抑制活性与它们的细胞死亡保护潜力相关。与Bcl-2一样，相关蛋白Bcl-xL而不是Bcl-xS能够抑制kB依赖的转录。Bcl-2通过一种不寻常的机制抑制NF-κ B活性。它不能阻止IkappaB在细胞质中的释放，但下调了核p65的反式激活潜力。这些数据表明NF-κ B可以参与细胞凋亡。我们认为，Bcl-2的抗凋亡潜力的至少一部分可以解释从迄今为止未发现的活性Bcl-2在控制核基因表达。
Among the many target genes of the transcription factor NF-kappaB are p53 and c-myc, both of which are involved in apoptosis. This prompted us to investigate the role of NF-kappaB in this process. We report that NF-kappaB is potently activated upon serum starvation, a condition leading to apoptosis in 293 cells. Similar to Bcl-2, a transdominant- negative mutant of the NF-kappaB p65 subunit partially inhibited apoptosis, indicating a direct involvement of the transcription factor in induction of cell death. As expected, the p65 mutant suppresses kappaB-dependent gene expression. Surprisingly, transiently or stably overexpressed Bcl-2 had the same effect. The transcription inhibitory activity of the two proteins correlated with their cell death protective potential. Like Bcl-2, the related protein Bcl-xL but not Bcl-xS was able to suppress kB-dependent transcription. Bcl-2 inhibited NF-kappaB activity by an unusual mechanism. It did not prevent the release of IkappaB in the cytoplasm but down-modulated the transactivating potential of nuclear p65. These data show that NF- kappaB can participate in apoptosis. We suggest that at least part of the anti-apoptotic potential of Bcl-2 may be explained from a hitherto undiscovered activity of Bcl-2 in controlling nuclear gene expression.