The codon 72 polymorphic variants of p53 have markedly different apoptotic potential
The codon 72 polymorphic variants of p53 have markedly different apoptotic potential
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DOI：
10.1038/ng1093
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发表时间：
2003-03-01
期刊：
影响因子：
30.8
通讯作者：
Murphy, M
中科院分区：
文献类型：
--
作者：
Dumont, P;Leu, JIJ;Murphy, M
编码p53的基因TP 53具有导致在氨基酸位置72处的脯氨酸或精氨酸的共同序列多态性。这种多态性发生在p53的富含脯氨酸的结构域，这是蛋白质完全诱导细胞凋亡所必需的。我们发现，在细胞系中含有可诱导版本的等位基因编码的Pro72和Arg 72的变体，并在细胞与内源性p53，Arg 72的变体诱导细胞凋亡显着优于Pro72的变体。我们的数据表明，这种增强的细胞凋亡潜力的至少一个来源是Arg 72变体定位于线粒体的能力更强;这种定位伴随着细胞色素c释放到胞质溶胶中。这些数据表明，p53的两种多态性变体在功能上是不同的，这些差异可能会影响癌症风险或治疗。
The gene TP53, encoding p53, has a common sequence polymorphism that results in either proline or arginine at amino-acid position 72. This polymorphism occurs in the proline-rich domain of p53, which is necessary for the protein to fully induce apoptosis. We found that in cell lines containing inducible versions of alleles encoding the Pro72 and Arg72 variants, and in cells with endogenous p53, the Arg72 variant induces apoptosis markedly better than does the Pro72 variant. Our data indicate that at least one source of this enhanced apoptotic potential is the greater ability of the Arg72 variant to localize to the mitochondria; this localization is accompanied by release of cytochrome c into the cytosol. These data indicate that the two polymorphic variants of p53 are functionally distinct, and these differences may influence cancer risk or treatment.