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Blood, 15 January 2006, Vol. 107, No. 2, pp. 508-513. Prepublished online as a Blood First Edition Paper on September 15, 2005; DOI 10.1182/blood-2005-07-2676. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-07-2676v1 107/2/508    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 Mirandola, P. Articles by Vitale, M. Search for Related Content PubMed PubMed Citation Articles by Mirandola, P. Articles by Vitale, M. Related Collections Hematopoiesis and Stem Cells Red Cells Apoptosis Signal Transduction Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS PKC controls protection against TRAIL in erythroid progenitors Prisco Mirandola, Giuliana Gobbi, Cristina Ponti, Ivonne Sponzilli, Lucio Cocco, and Marco Vitale From the Department of Anatomy, Pharmacology, & Forensic Medicine, Human Anatomy Section, University of Parma, Ospedale Maggiore, Parma, Italy; the Department of Normal Human Morphology, University of Trieste, Italy; the Department of Anatomical Sciences, Cellular Signaling Laboratory, University of Bologna, Italy; and Istituto per i Trapianti d'Organo e Immunocitologia–Consiglio Nazionale delle Ricerche (ITOI-CNR), Bologna Unit, Italy. Apoptosis plays a central role in the regulation of the size of the hematopoietic stem cell pool as well as in the processes of cell differentiation along the various hematopoietic lineages. TRAIL is a member of the TNF family of cytokines with a known apoptogenic role against a variety of malignant cells and an emerging role in the modulation of normal hematopoiesis. Here we worked on the hypothesis that PKC could act as a switch of the cellular response to TRAIL during erythropoiesis. We demonstrate that EPO-induced erythroid CD34 cells are insensitive to the apoptogenic effect of TRAIL at day 0 due to the lack of specific receptor expression. From day 3 onward, erythroid cells express surface death receptors and become sensitive to TRAIL up to day 7/8 when, notwithstanding death-receptor expression, the EPO-driven up-regulation of PKC intracellular levels renders differentiating erythroid cells resistant to TRAIL likely via Bcl-2 up-regulation. Our conclusion is that in human CD34 cells, EPO promotes a series of events that, being finely regulated in their kinetics, restricts the sensitivity of these cells to TRAIL to a specific period of time, which therefore represents the "TRAIL window" for the negative regulation of erythroid-cell numbers. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Closing the TRAIL to the DISC Robert T. Means, Jr Blood 2006 107: 418-419. [Full Text] [PDF] This article has been cited by other articles: G. Gobbi, P. Mirandola, C. Carubbi, C. Micheloni, C. Malinverno, P. Lunghi, A. Bonati, and M. Vitale Phorbol ester-induced PKC{epsilon} down-modulation sensitizes AML cells to TRAIL-induced apoptosis and cell differentiation Blood, March 26, 2009; 113(13): 3080 - 3087. [Abstract] [Full Text] [PDF] O. Bogacheva, O. Bogachev, M. Menon, A. Dev, E. Houde, E. I. Valoret, H. M. Prosser, C. L. Creasy, S. J. Pickering, E. Grau, et al. DYRK3 Dual-specificity Kinase Attenuates Erythropoiesis during Anemia J. Biol. Chem., December 26, 2008; 283(52): 36665 - 36675. [Abstract] [Full Text] [PDF] L. Zamai, C. Ponti, P. Mirandola, G. Gobbi, S. Papa, L. Galeotti, L. Cocco, and M. Vitale NK Cells and Cancer J. Immunol., April 1, 2007; 178(7): 4011 - 4016. [Abstract] [Full Text] [PDF]

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