Johnson Mark D, Wu Xiangwei, Aithmitti Nadia, Morrison Richard S
Department of Neurological Surgery, University of Washington School of Medicine, Box 356470, Seattle, Washington 98195-6470, USA.
J Biol Chem. 2002 Jun 21;277(25):23000-7. doi: 10.1074/jbc.M201907200. Epub 2002 Apr 9.
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.
DNA损伤后神经元细胞死亡需要p53和Bax，但p53激活导致Bax易位并引起神经元细胞死亡的机制尚不清楚。我们在此报告，Peg3/Pw1在p53依赖的方式下，在皮质神经元DNA损伤后上调。Peg3/Pw1的过表达导致神经元活力下降。p53或Bax的缺失消除了Peg3/Pw1对神经元存活的有害影响，表明两者在Peg3/Pw1介导的神经元死亡中起重要作用。此外，Peg3/Pw1显性负性蛋白的过表达抑制了DNA损伤后Bax的易位和神经元细胞死亡。这些发现表明，Peg3/Pw1在DNA损伤激活的神经元细胞死亡途径中是p53和Bax之间的介质。
