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This Article Full Text Full Text (PDF) 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 Lobmayr, L. Articles by Müllner, E. W. Search for Related Content PubMed PubMed Citation Articles by Lobmayr, L. Articles by Müllner, E. W. Related Collections Red Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 July 2002, Vol. 100, No. 1, pp. 289-298 RED CELLS Transferrin receptor hyperexpression in primary erythroblasts is lost on transformation by avian erythroblastosis virus Lioba Lobmayr, Thomas Sauer, Iris Killisch, Matthias Schranzhofer, Robert B. Wilson, Prem Ponka, Hartmut Beug, and Ernst W. Müllner From the Institute of Medical Biochemistry, Division of Molecular Biology and Institute of Molecular Pathology, Vienna Biocenter; Dr Bohr-Gasse, Vienna, Austria; Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia; and Lady Davis Institute for Medical Research, Jewish General Hospital, and the Departments of Physiology and Medicine, McGill University, Montreal, Quebec, Canada. In primary chicken erythroblasts (stem cell factor [SCF] erythroblasts), transferrin receptor (TfR) messenger RNA (mRNA) and protein were hyperexpressed as compared to nonerythroid chicken cell types. This erythroid-specific hyperexpression was abolished in transformed erythroblasts (HD3E22 cells) expressing the v-ErbA and v-ErbB oncogenes of avian erythroblastosis virus. TfR expression in HD3E22 cells could be modulated by changes in exogenous iron supply, whereas expression in SCF erythroblasts was not subject to iron regulation. Measurements of TfR mRNA half-life indicated that hyperexpression in SCF erythroblasts was due to a massive stabilization of transcripts even in the presence of high iron levels. Changes in mRNA binding activity of iron regulatory protein 1 (IRP1), the primary regulator of TfR mRNA stability in these cells, correlated well with TfR mRNA expression; IRP1 activity in HD3E22 cells and other nonerythroid cell types tested was iron dependent, whereas IRP1 activity in primary SCF erythroblasts could not be modulated by iron administration. Analysis of avian erythroblasts expressing v-ErbA alone indicated that v-ErbA was responsible for these transformation-specific alterations in the regulation of iron metabolism. In SCF erythroblasts high amounts of TfR were detected on the plasma membrane, but a large fraction was also located in early and late endosomal compartments, potentially concealing temporary iron stores from the IRP regulatory system. In contrast, TfR was almost exclusively located to the plasma membrane in HD3E22 cells. In summary, stabilization of TfR mRNA and redistribution of Fe-Tf/TfR complexes to late endosomal compartments may contribute to TfR hyperexpression in primary erythroblasts, effects that are lost on leukemic transformation. © 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: M. Schranzhofer, M. Schifrer, J. A. Cabrera, S. Kopp, P. Chiba, H. Beug, and E. W. Mullner Remodeling the regulation of iron metabolism during erythroid differentiation to ensure efficient heme biosynthesis Blood, May 15, 2006; 107(10): 4159 - 4167. [Abstract] [Full Text] [PDF]

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