title: Peg3/Pw1 promotes p53-mediated apoptosis by inducing Bax translocation from cytosol to mitochondria.
abstract: Mitochondria is believed to play a central role in p53-mediated apoptosis. However, the signal transduction pathways leading to mitochondria remain unclear. Here, we report that translocation of Bax protein from cytosol to mitochondria is required for p53-induced apoptosis. Cytosolic Bax is unable to induce apoptosis, and blocking Bax translocation inhibits cell death. Expression of Bcl-2 blocks cytochrome c release and apoptosis but has no effect on Bax translocation, suggesting that Bax translocation acts upstream of Bcl-2. We further demonstrate that Peg3/Pw1, a protein up-regulated in p53-mediated cell death process, induces Bax translocation independent of apoptosis. The results suggest that Bax translocation represents an important regulatory step in p53-mediated apoptosis, and Peg3/Pw1 functions as a modulator downstream of p53 to regulate Bax redistribution in the cells, thus favoring the cellular decision toward apoptosis over growth arrest following p53 induction.
authors.affiliation: Huffington Center on Aging, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Deng
authors.forename: X
authors.initials: X
authors.lastname: Wu
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D002460:Cell Line; D003574:Cytochrome c Group / Q000037:antagonists & inhibitors; D003600:Cytosol / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D021381:Protein Transport; D011506:Proteins / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2; D013347:Subcellular Fractions / Q000378:metabolism; D014157:Transcription Factors / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D051028:bcl-2-Associated X Protein
chemical_list: D003574:Cytochrome c Group; 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