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Blood, 1 October 2007, Vol. 110, No. 7, pp. 2361-2370. Prepublished online as a Blood First Edition Paper on June 4, 2007; DOI 10.1182/blood-2006-12-063503. This Article Full Text (PDF) Supplemental Appendix and Figures All Versions of this Article: blood-2006-12-063503v1 110/7/2361    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 December 21, 2006 Accepted May 26, 2007 EPO modulation of cell cycle regulatory genes, and cell division, in primary bone marrow erythroblasts Jing Fang, Madhu Menon, William Kapelle, Olga Bogacheva, Oleg Bogachev, Estelle Houde, Sarah Browne, Pradeep Sathyanarayana, and Don M Wojchowski* Program in Stem and Progenitor Cell Biology, Maine Medical Center Research Institute, Scarborough, ME, United States * Corresponding author; email: wojchd{at}mmc.org. EPO's actions on erythroblasts are ascribed largely to survival effects. Certain studies, however, point to EPO-regulated proliferation. To investigate this problem in a primary system, KitposCD71high erythroblasts were prepared from murine bone marrow, and were first used in the array-based discovery of EPO-modulated cell cycle regulators. Five cell cycle progression factors were rapidly up-modulated: nuclear protein 1 (Nupr1), G1 to S phase transition 1 (Gspt1), early growth response 1 (Egr1), Ngfi-A binding protein 2 (Nab2), and cyclin D2. In contrast, inhibitory cyclin G2, p27/Cdkn1b and B-cell leukemia/lymphoma 6(Bcl6) were sharply down-modulated. For CYCLIN G2, ectopic expression also proved to selectively attenuate EPO- dependent UT7epo cell cycle progression at S- phase. As analyzed in primary erythroblasts expressing minimal EPO receptor alleles, EPO- repression of cyclin G2 and Bcl6, and induction of cyclin D2, were determined to depend upon PY343- (and Stat5) signals. Furthermore, erythroblasts expressing a PY-null EPOR-HM allele were abnormally distributed in G0/G1. During differentiation divisions, EPOR-HM Ter119pos erythroblasts conversely accumulated in S-phase, and faltered in an apparent EPO-directed transition to G0/G1. EPO/EPOR signals therefore control the expression of select cell cycle regulatory genes which are proposed to modulate stage-specific decisions for erythroblast cell cycle progression. 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] P. Sathyanarayana, E. Houde, D. Marshall, A. Volk, D. Makropoulos, C. Emerson, A. Pradeep, P. J. Bugelski, and D. M. Wojchowski CNTO 530 functions as a potent EPO mimetic via unique sustained effects on bone marrow proerythroblast pools Blood, May 14, 2009; 113(20): 4955 - 4962. [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] M. A. Kerenyi, F. Grebien, H. Gehart, M. Schifrer, M. Artaker, B. Kovacic, H. Beug, R. Moriggl, and E. W. Mullner Stat5 regulates cellular iron uptake of erythroid cells via IRP-2 and TfR-1 Blood, November 1, 2008; 112(9): 3878 - 3888. [Abstract] [Full Text] [PDF] I. V. Libani, E. C. Guy, L. Melchiori, R. Schiro, P. Ramos, L. Breda, T. Scholzen, A. Chadburn, Y. Liu, M. Kernbach, et al. Decreased differentiation of erythroid cells exacerbates ineffective erythropoiesis in {beta}-thalassemia Blood, August 1, 2008; 112(3): 875 - 885. [Abstract] [Full Text] [PDF] J. Fang, M. Menon, D. Zhang, B. Torbett, L. Oxburgh, M. Tschan, E. Houde, and D. M. Wojchowski Attenuation of EPO-dependent erythroblast formation by death-associated protein kinase-2 Blood, August 1, 2008; 112(3): 886 - 890. [Abstract] [Full Text] [PDF] P. Sathyanarayana, A. Dev, J. Fang, E. Houde, O. Bogacheva, O. Bogachev, M. Menon, S. Browne, A. Pradeep, C. Emerson, et al. EPO receptor circuits for primary erythroblast survival Blood, June 1, 2008; 111(11): 5390 - 5399. [Abstract] [Full Text] [PDF] F. Grebien, M. A. Kerenyi, B. Kovacic, T. Kolbe, V. Becker, H. Dolznig, K. Pfeffer, U. Klingmuller, M. Muller, H. Beug, et al. Stat5 activation enables erythropoiesis in the absence of EpoR and Jak2 Blood, May 1, 2008; 111(9): 4511 - 4522. [Abstract] [Full Text] [PDF]

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