Involvement of Bcl-2 family proteins in p53-induced apoptosis.
Involvement of Bcl-2 family proteins in p53-induced apoptosis.
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DOI：
10.1272/jnms.72.192
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发表时间：
2005-08-01
期刊：
影响因子：
--
通讯作者：
Tobiume, Kei
中科院分区：
文献类型：
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作者：
Tobiume, Kei
p53肿瘤抑制基因的突变发生在超过50%的人类癌症中。响应于各种细胞应激，如DNA损伤，p53蛋白通过转录后机制快速积累，并激活在细胞反应中起主要作用的基因的表达，导致细胞周期停滞，DNA修复和细胞凋亡作为转录激活剂。特别地，细胞凋亡的诱导被认为是p53抑制肿瘤的重要功能。最近，Bcl-2家族的两个仅含BH 3的成员Noxa和PUMA已被确定为p53靶基因。此外，对多结构域Bcl-2家族蛋白Bax和巴克双重缺陷的小鼠的分析显示，由仅BH 3蛋白诱导的细胞凋亡完全依赖于Bax和巴克。最近，使用基因敲除小鼠证明Noxa和NoxA作为p53诱导的细胞凋亡的效应物起作用。这些分析表明，p53诱导的细胞凋亡是由这些Bcl-2家族蛋白调节。在这张照相凹版中，这些Bcl-2家族蛋白在p53诱导的细胞凋亡中的调节是通过荧光蛋白融合和免疫荧光方法可视化的。
Mutations in the p53 tumor suppressor gene occur in more than 50% of human cancers. In response to various cellular stresses, such as DNA damage, the p53 protein rapidly accumulates by posttranscriptional mechanism(s) and activates the expression of genes that play a major role in cellular responses leading to cell cycle arrest, DNA repair and apoptosis as a transcriptional activator. In particular, the induction of apoptosis is considered to be an important function in tumor suppression by p53. Recently, two BH3-only members of the Bcl-2 family, Noxa and PUMA, have been identified as p53 target genes. Furthermore, the analysis of mice doubly deficient in multidomain Bcl-2 family proteins, Bax and Bak, revealed that apoptosis induced by the BH3-only protein is completely dependent on Bax and Bak. More recently, it was demonstrated using gene knockout mice that Noxa and PUMA function as the effectors of p53-induced apoptosis. These analyses revealed that p53-induced apoptosis is regulated by these Bcl-2 family proteins. In this photogravure, the regulation of these Bcl-2 family proteins in p53-induced apoptosis was visualized by fluorescent protein fusion and immune fluorescence methods.