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Prepublished online as a Blood First Edition Paper on July 18, 2002; DOI 10.1182/blood-2002-02-0504. This Article Full Text Full Text (PDF) Erratum (v101,p2114) All Versions of this Article: 2002-02-0504v1 100/12/3990    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Lin, Y. Articles by Benchimol, S. Search for Related Content PubMed PubMed Citation Articles by Lin, Y. Articles by Benchimol, S. Related Collections Hematopoiesis and Stem Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 December 2002, Vol. 100, No. 12, pp. 3990-4000 HEMATOPOIESIS The death-promoting activity of p53 can be inhibited by distinct signaling pathways Yunping Lin, Lauren Brown, David W. Hedley, Dwayne L. Barber, and Samuel Benchimol From the Ontario Cancer Institute and Departments of Medical Biophysics, and Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada. Various cytokines have been shown to protect cells from p53-dependent apoptosis. To investigate the mechanism underlying cytokine-mediated survival, we used a Friend virus-transformed erythroleukemia cell line that expresses a temperature-sensitive p53 allele. These cells express the spleen focus-forming virus-encoded envelope glycoprotein gp55 that allows the cells to proliferate in the absence of erythropoietin (EPO). These cells respond to p53 activation at 32°C by undergoing G1 cell cycle arrest and apoptosis. In the presence of EPO, p53 activation leads only to prolonged but viable G1 arrest. These findings indicate that EPO functions as a survival factor and that gp55/EPO receptor signaling is distinct from EPO/EPO receptor signaling. We demonstrate that p53-dependent apoptosis results in mitochondrial damage as shown by loss of mitochondrial membrane potential, increase in intracellular calcium, and release of mitochondrial cytochrome c into the cytosol. EPO prevented all of these changes including the subsequent activation of caspases. We identify an intrinsic phosphatidylinositol-3'-OH kinase/protein kinase B (PI3'K/PKB)-dependent survival pathway that is constitutively active in these cells. This survival pathway limits p53-dependent apoptosis. We propose that EPO promotes survival through a distinct pathway that is dependent on JAK2 but independent of STAT5 and PI3'K. © 2002 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. Brown and S. Benchimol The Involvement of MAPK Signaling Pathways in Determining the Cellular Response to p53 Activation: CELL CYCLE ARREST OR APOPTOSIS J. Biol. Chem., February 17, 2006; 281(7): 3832 - 3840. [Abstract] [Full Text] [PDF] C. J. Parsa, J. Kim, R. U. Riel, L. S. Pascal, R. B. Thompson, J. A. Petrofski, A. Matsumoto, J. S. Stamler, and W. J. Koch Cardioprotective Effects of Erythropoietin in the Reperfused Ischemic Heart: A POTENTIAL ROLE FOR CARDIAC FIBROBLASTS J. Biol. Chem., May 14, 2004; 279(20): 20655 - 20662. [Abstract] [Full Text] [PDF] B. E. Barton, J. G. Karras, T. F. Murphy, A. Barton, and H. F-S. Huang Signal transducer and activator of transcription 3 (STAT3) activation in prostate cancer: Direct STAT3 inhibition induces apoptosis in prostate cancer lines Mol. Cancer Ther., January 1, 2004; 3(1): 11 - 20. [Abstract] [Full Text]

	Copyright © 2002 by American Society of Hematology         Online ISSN: 1528-0020