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Blood, 1 November 2008, Vol. 112, No. 9, pp. 3878-3888. Prepublished online as a Blood First Edition Paper on August 11, 2008; DOI 10.1182/blood-2008-02-138339. This Article Full Text Full Text (PDF) Supplemental Methods, Table, and Figures All Versions of this Article: blood-2008-02-138339v1 112/9/3878    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 Kerenyi, M. A. Articles by Müllner, E. W. Search for Related Content PubMed PubMed Citation Articles by Kerenyi, M. A. Articles by Müllner, E. W. Related Collections Red Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS Stat5 regulates cellular iron uptake of erythroid cells via IRP-2 and TfR-1 Marc A. Kerenyi1,*, Florian Grebien1,*, Helmuth Gehart1, Manfred Schifrer1, Matthias Artaker1, Boris Kovacic2, Hartmut Beug2, Richard Moriggl3, and Ernst W. Müllner1 1 Max F. Perutz Laboratories, Department of Medical Biochemistry, Medical University of Vienna, Vienna; 2 Research Institute of Molecular Pathology, Vienna; and 3 Ludwig Boltzmann Institute for Cancer Research, Vienna, Austria Erythropoiesis strictly depends on signal transduction through the erythropoietin receptor (EpoR)–Janus kinase 2 (Jak2)–signal transducer and activator of transcription 5 (Stat5) axis, regulating proliferation, differentiation, and survival. The exact role of the transcription factor Stat5 in erythropoiesis remained puzzling, however, since the first Stat5-deficient mice carried a hypomorphic Stat5 allele, impeding full phenotypical analysis. Using mice completely lacking Stat5—displaying early lethality—we demonstrate that these animals suffer from microcytic anemia due to reduced expression of the antiapoptotic proteins Bcl-xL and Mcl-1 followed by enhanced apoptosis. Moreover, transferrin receptor-1 (TfR-1) cell surface levels on erythroid cells were decreased more than 2-fold on erythroid cells of Stat5–/– animals. This reduction could be attributed to reduced transcription of TfR-1 mRNA and iron regulatory protein 2 (IRP-2), the major translational regulator of TfR-1 mRNA stability in erythroid cells. Both genes were demonstrated to be direct transcriptional targets of Stat5. This establishes an unexpected mechanistic link between EpoR/Jak/Stat signaling and iron metabolism, processes absolutely essential for erythropoiesis and life. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: P. Robach, S. Recalcati, D. Girelli, C. Gelfi, N. J. Aachmann-Andersen, J. J. Thomsen, A. M. Norgaard, A. Alberghini, N. Campostrini, A. Castagna, et al. Alterations of systemic and muscle iron metabolism in human subjects treated with low-dose recombinant erythropoietin Blood, June 25, 2009; 113(26): 6707 - 6715. [Abstract] [Full Text] [PDF] A. Iolascon, L. De Falco, and C. Beaumont Molecular basis of inherited microcytic anemia due to defects in iron acquisition or heme synthesis Haematologica, March 1, 2009; 94(3): 395 - 408. [Abstract] [Full Text] [PDF]

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