p53RDL1 regulates p53-dependent apoptosis
p53RDL1 regulates p53-dependent apoptosis
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DOI：
10.1038/ncb943
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发表时间：
2003-03-01
影响因子：
21.3
通讯作者：
Arakawa, H
中科院分区：
文献类型：
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作者：
Tanikawa, C;Matsuda, K;Arakawa, H
虽然已经报道了许多p53的靶点，但p53依赖性细胞凋亡的机制仍有待阐明。在这里，我们报告了一个新的p53靶基因，命名为p53 RDL 1（p53调节的死亡和生命受体，也称为UNC 5 B）。p53 RDL 1基因产物含有与大鼠Unc 5 H2高度同源的细胞质羧基末端死亡结构域，Unc 5 H2是一种参与细胞凋亡调节以及神经细胞轴突导向和迁移的依赖性受体（1）。我们发现p53 RDL 1介导了p53依赖的细胞凋亡。相反，当p53 RDL 1与其配体Netrin-1相互作用时，p53依赖性凋亡被阻断。因此，p53 RDL 1似乎是一个以前未被认识的p53靶点，可能定义了一个新的p53依赖性细胞凋亡途径。我们认为，p53可能通过平衡Netrin-p53 RDL 1信号传导的调节来调节受损细胞的存活，并通过裂解p53 RDL 1进行细胞凋亡来调节细胞死亡。
Although a number of targets for p53 have been reported, the mechanism of p53-dependent apoptosis still remains to be elucidated. Here we report a new p53 target-gene, designated p53RDL1 (p53-regulated receptor for death and life; also termed UNC5B). The p53RDL1 gene product contains a cytoplasmic carboxy-terminal death domain that is highly homologous to rat Unc5H2, a dependence receptor involved in the regulation of apoptosis, as well as in axon guidance and migration of neural cells(1). We found that p53RDL1 mediated p53-dependent apoptosis. Conversely, when p53RDL1 interacted with its ligand, Netrin-1, p53-dependent apoptosis was blocked. Therefore, p53RDL1 seems to be a previously un-recognized target of p53 that may define a new pathway for p53-dependent apoptosis. We suggest that p53 might regulate the survival of damaged cells by balancing the regulation of Netrin-p53RDL1 signalling, and cell death through cleavage of p53RDL1 for apoptosis.