Pw1/Peg3 is a potential cell death mediator and cooperates with Siah1a in p53-mediated apoptosis.
Induction of wild-type p53 in mouse fibroblasts causes cell cycle arrest at the G(1) phase, whereas coexpression of p53 and the protooncogene c-myc induces apoptosis. Although p53 transcriptional activity generally is required for both pathways, the molecular components mediating p53-dependent apoptosis are not well understood. To identify factors that could mediate p53-induced cell death, we used a comparative RNA differential display procedure. We have identified Pw1/Peg3 as a gene product induced during p53/c-myc-mediated apoptosis. Pw1/Peg3 is not induced during p53-mediated G(1) growth arrest nor by c-myc alone. Although it is not clear whether the induction of Pw1/Peg3 depends on p53 activity, we show that Pw1/Peg3 interacts with a p53-inducible gene product Siah1a. We demonstrate that coexpression of Pw1/Peg3 with Siah1a induces apoptosis independently of p53 whereas expression of Pw1/Peg3 or Siah1a separately has no effect on cell death. These data suggest that Siah1a and Pw1/Peg3 cooperate in the p53-mediated cell death pathway. Furthermore, we show that inhibiting Pw1/Peg3 activity blocks p53-induced apoptosis. The observation that Pw1/Peg3 is necessary for the p53 apoptotic response suggests a pivotal role for this gene in determining cell death versus survival.
Relaix
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F
The Derald H. Ruttenberg Cancer Center, The Brookdale Center for Molecular and Developmental Biology, The Mount Sinai Medical Center, New York, NY 10029, USA.
Wei
X j
Xj
Li
W
W
Pan
J
J
Lin
Y
Y
Bowtell
D D
DD
Sassoon
D A
DA
Wu
X
X
D016475:3T3 Cells; D000818:Animals; D017209:Apoptosis; D015870:Gene Expression; D006801:Humans; D051741:Kruppel-Like Transcription Factors; D051379:Mice; D016296:Mutagenesis; D009687:Nuclear Proteins / Q000378:metabolism*; D011494:Protein Kinases; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D016372:RNA, Antisense; D012333:RNA, Messenger; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases; D000098563:Seven in Absentia Proteins
D051741:Kruppel-Like Transcription Factors; D009687:Nuclear Proteins; C490820:PEG3 protein, human; C097901:Peg3 protein, mouse; D011506:Proteins; D016271:Proto-Oncogene Proteins c-myc; D016372:RNA, Antisense; D012333:RNA, Messenger; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D044767:Ubiquitin-Protein Ligases; D000098563:Seven in Absentia Proteins; D011494:Protein Kinases