Peg3/Pw1 is a mediator between p53 and Bax in DNA damage-induced neuronal death.
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.
Johnson
Mark D
MD
Department of Neurological Surgery, University of Washington School of Medicine, Box 356470, Seattle, Washington 98195-6470, USA.
Wu
Xiangwei
X
Aithmitti
Nadia
N
Morrison
Richard S
RS
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D015153:Blotting, Western; D016923:Cell Death; D002470:Cell Survival; D004249:DNA Damage; D006801:Humans; D007150:Immunohistochemistry; D051741:Kruppel-Like Transcription Factors; D051379:Mice; D008810:Mice, Inbred C57BL; D008858:Microscopy, Phase-Contrast; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism; D011485:Protein Binding; D011494:Protein Kinases; D021381:Protein Transport; D011506:Proteins / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism*; D014161:Transduction, Genetic; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; C494827:Bax protein, mouse; D051741:Kruppel-Like Transcription Factors; C490820:PEG3 protein, human; C097901:Peg3 protein, mouse; D011506:Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D011494:Protein Kinases