p53AlP1, a potential mediator of p53-dependent apoptosis, and its regulation by Ser-46-phosphorylated p53
p53AlP1, a potential mediator of p53-dependent apoptosis, and its regulation by Ser-46-phosphorylated p53
复制标题
DOI：
10.1016/s0092-8674(00)00073-8
复制
发表时间：
2000-09-15
期刊：
影响因子：
64.5
通讯作者：
Taya, Y
中科院分区：
文献类型：
--
作者：
Oda, K;Arakawa, H;Taya, Y
通过从人类基因组DNA中直接克隆p53结合序列，我们已经分离出一个新的基因，命名为p53 AIP 1（p89调节凋亡诱导蛋白1），其表达是由野生型p53诱导。异位表达的p53 AIP 1定位于线粒体内，通过线粒体Δ psi m的耗散导致凋亡性细胞死亡。我们已经发现，在严重的DNA损伤时，p53上的Ser-46被磷酸化并诱导细胞凋亡。此外，Ser-46的取代抑制了p53诱导凋亡的能力，并选择性地阻断了p53 AIP 1的表达。我们的研究结果表明，p53 AIP 1可能在介导p53依赖性细胞凋亡中发挥重要作用，Ser-46磷酸化调节该细胞凋亡诱导基因的转录激活。
Through direct cloning of p53 binding sequences from human genomic DNA, we have isolated a novel gene, designated p53AIP1 (p89-regulated Apoptosis-Inducing Protein 1), whose expression is inducible by wildtype p53. Ectopically expressed p53AIP1, which is localized within mitochondria, leads to apoptotic cell death through dissipation of mitochondrial Delta psi m. We have found that upon severe DNA damage, Ser-46 on p53 is phosphorylated and apoptosis is induced. In addition, substitution of Ser-46 inhibits the ability of p53 to induce apoptosis and selectively blocks expression of p53AIP1. Our results suggest that p53AIP1 is likely to play an important role in mediating p53-dependent apoptosis, and phosphorylation of Ser-46 regulates the transcriptional activation of this apoptosis-inducing gene.