Diminished cell proliferation associated with the death-protective activity of Bcl-2
Diminished cell proliferation associated with the death-protective activity of Bcl-2
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DOI：
10.1074/jbc.271.22.12695
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发表时间：
1996-05-31
影响因子：
4.8
通讯作者：
Borner, C
中科院分区：
文献类型：
--
作者：
Borner, C
癌基因产物Bcl-2有效地使细胞免于程序性细胞死亡（凋亡）。然而，这种死亡保护活性的分子机制仍然是个谜。在这里，我们表明，诱导Bcl-2的表达始终与哺乳动物细胞增殖的延迟，由于细胞周期的G（1）期的延长。缺乏Bcl-2表达的细胞在细胞周期的任何时间点响应于凋亡剂而死亡，而Bcl-2过表达的细胞在G（0）/G（1）期积累并被保护免于细胞死亡。Bcl-2的负调节因子Bax的共表达逆转了Bcl-2的细胞死亡保护和增殖抑制活性。此外，在死亡保护中有缺陷的Bcl-2突变体不影响细胞分裂。这些发现表明Bcl-2通过降低细胞增殖速率而有助于细胞存活。
The oncogene product Bcl-2 effectively spares cells from programmed cell death (apoptosis). The molecular mechanism underlying this death-protective activity has, however, remained enigmatic. Here we show that induction of Bcl-2 expression is consistently associated with a retardation of mammalian cell proliferation due to a prolongation of the G(1) phase of the cell cycle. Whereas cells lacking Bcl-2 expression die from any point of the cell cycle in response to apoptotic agents, Bcl-2-overexpressing cells accumulate in the G(0)/G(1) phase and are protected from cell death. Co-expression of Bax, a negative regulator of Bcl-2, reverts both the cell death protective and proliferation retarding activities of Bcl-2. Moreover, a Bcl-2 mutant defective in death protection does not affect cell division. These findings indicate that Bcl-2 contributes to cell survival by diminishing the rate of cell proliferation.