Bcl-2 and Bax proteins are present in interphase nuclei of mammalian cells
Bcl-2 and Bax proteins are present in interphase nuclei of mammalian cells
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DOI：
10.1038/sj.cdd.4400664
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发表时间：
2000-04-01
影响因子：
12.4
通讯作者：
van Dierendonck, JH
中科院分区：
文献类型：
--
作者：
Hoetelmans, RWM;van Slooten, HJ;van Dierendonck, JH
Bcl-2蛋白家族包括细胞死亡抑制和细胞死亡促进成员，通常认为是细胞质的并且主要是膜相关的。像Bcl-2一样，许多Bcl-2相关蛋白含有C-末端膜插入结构域，许多研究旨在评估其定位于线粒体外膜、内质网和核周膜的功能作用。然而，共聚焦荧光显微镜的人乳腺癌细胞和大鼠结肠癌细胞的免疫染色与商业抗体提出的抗凋亡Bcl-2和促凋亡Bax蛋白的不同表位显示，这些蛋白质不仅存在于细胞质中，而且在间期核内。这通过分离的细胞核的蛋白质印迹分析证实。在人类细胞中，Bcl-2的某些表位，而不是Bax，也被发现与有丝分裂染色质。抗雌激素治疗人乳腺癌细胞或转染反义bcl-2导致细胞质和细胞核Bcl-2的减少。将人bcl-2和bax基因转染到大鼠细胞中，导致细胞质和细胞核中的Bcl-2和Bax。这一数据似乎与越来越多的证据一致，即Bcl-2蛋白家族的作用应该扩展到核室内的活动。
The Bcl-2 family of proteins comprises both cell death inhibiting and cell death promoting members, generally believed to be cytoplasmic and predominantly membrane-associated. Like Bcl-2, many Bcl-2-related proteins contain a C-terminal membrane insertion domain and much research is aimed at evaluating the functional role of their localization to the outer membranes of mitochondria, the endoplasmic reticulum, and perinuclear membranes. However, confocal fluorescence microscopy of human breast cancer cells and rat colon cancer cells immunostained with commercial antibodies raised against different epitopes of the anti-apoptotic Bcl-2 and the pro-apoptotic Bax protein revealed that these proteins are not only present in the cellular cytoplasm, but also within interphase nuclei. This was confirmed by Western blot analysis of isolated nuclei. In human cells, certain epitopes of Bcl-2, but not of Bax, were also found to be associated with mitotic chromatin. Anti-estrogen treatment of human breast cancer cells or transfection with antisense bcl-2 led to a reduction in both cytoplasmic and nuclear Bcl-2. Transfection of human bcl-2 and bax into rat cells resulted in cytoplasmic and nuclear Bcl-2 and Bax. This data seems in line with increasing evidence that the role of the Bcl-2 family of proteins should be extended to activities inside the nuclear compartment.