Suppression of apoptosis by Bcl-2 or Bcl-xL promotes susceptibility to mutagenesis.
Suppression of apoptosis by Bcl-2 or Bcl-xL promotes susceptibility to mutagenesis.
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DOI：
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发表时间：
1996-10
期刊：
影响因子：
8
通讯作者：
C. Cherbonnel-Lasserre;S. Gauny;A. Kronenberg
中科院分区：
文献类型：
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作者：
C. Cherbonnel-Lasserre;S. Gauny;A. Kronenberg
Bcl-2似乎主要通过促进细胞存活而不是通过刺激细胞增殖来促成瘤形成。Bcl-2和相关蛋白Bcl-xL各自抑制许多不同细胞类型中由各种各样的刺激诱导的凋亡。在这里，我们报告说，抑制凋亡Bcl-2或Bcl-xL显着提高辐射诱导的突变的水平。这种增强的诱变是突变频率（每个存活者的突变）增加以及生存力适度增加的结果。Bcl-2或Bcl-xL的异位表达增强具有wtp 53的细胞中的辐射诱变。令人惊讶的是，我们发现Bcl-xL的异位表达也促进了p53-细胞的突变。这些结果支持了这样的假设，即细胞凋亡在通过选择性地从群体中消除高度突变的细胞来维持基因组完整性方面起着至关重要的作用。
Bcl-2 appears to contribute to neoplasia primarily by promoting cell survival, rather than by stimulating cellular proliferation. Bcl-2, and the related protein Bcl-xL, each suppress apoptosis induced by a wide variety of stimuli in many different cell types. Here we report that suppression of apoptosis by Bcl-2 or Bcl-xL markedly elevates the levels of radiation-induced mutations. This enhanced mutagenesis is the result of an increase in mutation frequency (mutations per survivor) together with a moderate increase in viability. Ectopic expression of either Bcl-2 or Bcl-xL enhances radiation mutagenesis in cells with wtp53. Surprisingly, we found that ectopic expression of Bcl-xL also promotes mutagenesis in p53- cells. These results support the hypothesis that apoptosis plays a crucial role in maintaining genomic integrity by selectively eliminating highly mutated cells from the population.