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Blood, 1 August 2008, Vol. 112, No. 3, pp. 886-890. Prepublished online as a Blood First Edition Paper on June 5, 2008; DOI 10.1182/blood-2008-02-138909. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-02-138909v1 112/3/886    most recent Alert me when this article is cited Alert me if a correction is posted 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 Fang, J. Articles by Wojchowski, D. M Search for Related Content PubMed PubMed Citation Articles by Fang, J. Articles by Wojchowski, D. M Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 12, 2008 Accepted May 19, 2008 Attenuation of EPO-dependent erythroblast formation by death associated protein kinase-2 Jing Fang, Madhu Menon, Diya Zhang, Bruce Torbett, Leif Oxburgh, Mario Tschan, Estelle Houde, and Don M Wojchowski* Stem & Progenitor Cell Biology Program, Maine Medical Center Research Institute, Scarborough, Maine, United States Department of Statistics, Northwestern University, Evanston, IL, United States Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, United States * Corresponding author; email: wojchd{at}mmc.org. The adult erythron is maintained via dynamic modulation of erythroblast survival potentials. Towards identifying novel regulators of this process, murine splenic erythroblasts at three developmental stages were prepared, purified and profiled. Stage-to-stage modulated genes were then functionally categorized, with a focus on apoptotic factors. In parallel with BCL-X and NIX, death-associated protein kinase-2 (DAPK2) was substantially up-modulated during late erythropoiesis. Among hematopoietic lineages, DAPK2 was expressed predominantly in erythroid cells. In a Gata1-IE3.9int-DAPK2 transgenic mouse model, effects on steady-state reticulocytes and RBC levels were limited. During hemolytic anemia, however, erythropoiesis was markedly deficient. Ex vivo analyses revealed heightened apoptosis due to DAPK2 at a KitnegCD71highTer119neg stage, together with a subsequent multi-fold defect in late-stage KitnegCD71highTer119pos cell formation. In UT7epo cells, siRNA knock-down of DAPK2 enhanced survival due to cytokine withdrawal, and DAPK2's phosphorylation and kinase activity also were EPO-modulated. DAPK2 therefore comprises a new candidate attenuator of stress erythropoiesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. C. MacNamara, R. Racine, M. Chatterjee, D. Borjesson, and G. M. Winslow Diminished Hematopoietic Activity Associated with Alterations in Innate and Adaptive Immunity in a Mouse Model of Human Monocytic Ehrlichiosis Infect. Immun., September 1, 2009; 77(9): 4061 - 4069. [Abstract] [Full Text] [PDF]

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