Peg3/Pw1 is a mediator between p53 and Bax in DNA damage-induced neuronal death
Peg3/Pw1 is a mediator between p53 and Bax in DNA damage-induced neuronal death
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DOI：
10.1074/jbc.m201907200
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发表时间：
2002-06-21
影响因子：
4.8
通讯作者：
Morrison, RS
中科院分区：
文献类型：
--
作者：
Johnson, MD;Wu, XW;Morrison, RS
DNA损伤后的神经细胞死亡需要P53和Bax，但P53激活导致Bax易位和神经细胞死亡的机制尚不清楚。我们在这里报道，在DNA损伤后，Peg3/Pw1在大脑皮层神经元中以P53依赖的方式上调。Peg3/Pw1过表达导致神经元存活率下降。Peg3/Pw1对神经元存活的有害影响可以通过P53或Bax的缺失而消除，这表明两者在Peg3/Pw1介导的神经元死亡中都发挥了重要作用。此外，过表达Peg3/Pw1显性负蛋白可抑制DNA损伤后Bax易位和神经细胞死亡。这些发现表明，Peg3/Pw1在DNA损伤激活的神经细胞死亡途径中是P53和Bax之间的中介。
Neuronal cell death after DNA damage requires p53 and Bax, but the mechanism by which p53 activation leads to Bax translocation and cell death in neurons is not known. We report here that Peg3/Pw1 is up-regulated after DNA damage in cortical neurons in a p53-dependent manner. Overexpression of Peg3/Pw1 leads to decreased neuronal viability. The deleterious effect of Peg3/Pw1 on neuronal survival is abrogated by deletion of either p53 or Bax, indicating an essential role for both in Peg3/Pw1-mediated neuronal death. Moreover, overexpression of a Peg3/Pw1 dominant negative protein inhibits Bax translocation and neuronal cell death after DNA damage. These findings implicate Peg3/Pw1 as a mediator between p53 and Bax in a neuronal cell death pathway activated by DNA damage.